The Canadian Cardiac Chronicle Summer 2014
Volume 18, No. 2 By the time this special issue of the Chronicle reaches your desk and/or computer screen, the summer solstice will be in your neighbourhood and ours. It is extraordinary to reflect that the tilt of our planet is then most inclined toward the sun (a tilt that maximizes at 23º 26’). As a result, the land of the midnight sun in the Arctic Circle at 66º56’N is in full illumination. For those of us living a bit south of the Arctic Circle at 53º27’N in Edmonton Alberta, we will celebrate over 17 hours of daylight as compared to the approximate 7.5 hours we have on December 21st. Stimulated by the increasing illumination this time of year brings, we are energized to provide you this edition of the Chronicle, chock-full of interesting and new information about CVC. There are four matters that I think are worthy of special note: 1. In March of this year, in conjunction with the ACC Rockies educational event chaired by Robert Welsh, we held a Clinical Trials Colloquium. Our purpose was to generate dialogue on the key issues that affect our clinical trial activities in Canada, and then to examine how best to overcome any impediments to pursuing our pathway to discovering better cardiovascular health. It was a remarkable meeting, with great representation from across the country that resulted in vigorous participation and good ideas and suggestions as summarized elsewhere in the Chronicle. We are most grateful for the sponsorship of Amgen, AstraZeneca, Merck Canada and Sanofi-aventis in support of this endeavour. Special thanks to Tracy Temple for her organizational leadership of the event and to Justin Ezekowitz, Shaun Goodman and Lisa Berdan for their collaboration in developing this inaugural program. 2. The second matter relates to our growing academic partnerships with our friends and colleagues south of the border. For well over a decade, we have had an outstanding collaboration and master clinical research agreement with the Duke Clinical Research Institute. This partnership has facilitated the development of a strong academic thought leadership, focused on the enhancement of patient care and health care systems through the generation, translation and dissemination
The CVC is proud to be a University of Alberta Centre
In This issue: Letter - P.W. Armstrong Trial Updates Beyond 2000 CVC Clincial Trial Research Colloquium CVC Publications
1-2 3-8 9 10-11 12
of new knowledge. This partnering has facilitated the sharing of clinical trial data and the incorporation of innovative high quality research across the full investigative spectrum. It has also provided training and mentoring of young clinician scientists, many of whom have trained at the Duke Clinical Research Institute and then returned to centres in Canada, including the University of Toronto, the University of Alberta, and elsewhere. Two years ago, the then Duke Clinical Research Institute Director Robert Harrington, moved to Stanford University and assumed the Chair of Medicine; subsequently he was joined by Ken Mahaffey from DCRI. As a result, over the past year, we have worked towards a new academic research collaboration facilitating both North/South and East/West connectivity. This exciting opportunity will unquestionably enrich our opportunities, capacity and creativity as the clinical research agenda environment evolves in the times ahead. Visible evidence of this collaboration is provided within this issue of the Chronicle. We were delighted to host a visit from Eric Peterson, Director of Duke Clinical Research Institute and Lisa Berdan, Director of Global Mega-Trials at Duke Clinical Research Institute in March who then joined us subsequently at the Research Colloquium and ACC Rockies meeting. In the subsequent month, we were pleased to welcome Robert Harrington, The Arthur L. Bloomfield Professor of Medicine, Chairman, Department of Medicine at Stanford and gain his perspective not only on the future of cardiovascular clinical trials but also to present our own research
The Canadian Cardiac Chronicle - Volume 18
Director’s Message Continued... in progress and potential directions for future collaborations. Our outreach through future colloquia and CME events, our re-engineering of academic partnerships through a collaborative North American academic research association are all auspicious signals of our unrelenting pursuit of excellence. 3. Thirdly, as we look ahead to the annual Canadian Cardiovascular Society meeting in Vancouver next October, we recognize this will represent a special 20th anniversary for our New Concepts in Acute Coronary Syndromes: Beyond 2000 program. This traditional program is a well-regarded legacy during which we meet many of our Canadian colleagues. It again promises to be a terrific event that is now enhanced by archiving the presentations and video interviews on the Beyond 2000 website (http://www.beyond2000.org) for reviewing at your leisure. We encourage our colleagues across the country to register on the web site in advance. More details can be found inside this issue of the Chronicle.
Professor at the University of Alberta. Shaun is the academic lead on both the EXSCEL and ODYSSEY. All of these as well as our other projects are highlighted elsewhere in the Chronicle. Our new management board, chaired by myself as Founding Director will consist of our two co-directors and other three key team leads; Dianne Payeur, Assistant Director of Finance/ Operations, Tracy Temple, Assistant Director, Clinical Trials, Cindy Westerhout, Assistant Director, Biostatistics. This organizational re-structuring positions us well to pursue our central purpose of enhancing cardiovascular health for current and future generations. We wish our many friends and collaborators a happy summer or solstice wherever on planet earth this finds you. With kind regards,
Paul W. Armstrong
4. Finally, as we move through the solstice towards the beginning of a new academic year in July, we look forward to the emergence of more active roles and leadership from our two CVC Co-Directors announced last October. Justin Ezekowitz, here at the University of Alberta, currently the academic lead on GUIDE-IT, SODIUM-HF and BLAST-AHF will assume a direct day-to-day role in CVC activities. He will be ably supported by Shaun Goodman at the University of Toronto and Adjunct
DCRI Visit - March 6-7th, 2014
Robert Harrington (Stanford) - April 16th, 2014
Back row, left to right: Justin Ezekowitz, Lisa Berdan, Suzanne Pfeifer, Robert Welsh, Kevin Bainey, Carla Price
Left to right: Justin Ezekowitz, Tracy Temple, Robert Harrington, Paul W. Armstrong, Padma Kaul, Dianne Payeur
Front row, left to right: Dianne Payeur, Eric Peterson, Paul W. Armstrong, Tracy Temple, Padma Kaul
Page 2
The Canadian Cardiac Chronicle - Volume 18
EXSCEL The EXSCEL trial has now enrolled almost 10,000 patients worldwide, of which over 400 were enrolled in Canada. Welcome to our new sites who have recently joined the study in Canada. We look forward to having our new sites activated in the near future and are confident that these additional sites will bolster our enrollment numbers as we move closer to reaching our final enrollment goal. Congratulations to our top 5 recruiting sites of 2014 (data as of May 31, 2014): • PI Dr. Francois Dubé – SC Marilène Bolduc – 11 patients enrolled in 2014 • PI Dr. Steven Cheung – SC Tracy Cleveland – 6 patients enrolled in 2014 • PI Dr. Zubin Punthakee – SC Irene Stanton – 6 patients enrolled in 2014 • PI Dr. Robin Kuritzky – SC Carol Marchand – 4 patients enrolled in 2014 Thank you for your continued support of the EXSCEL trial – your efforts are much appreciated! Amendment 5 has received Health Canada approval and we anticipate that the majority of our sites will be actively working under the amendment by the end of June. As this amendment includes a number of new patient and site materials, please make sure you are familiar with them and use them to your advantage! A reminder that all patient materials must be submitted to your REB and receive approval prior to use with
patients at your site. Please ensure that a copy of all of your REB approvals is sent to your CVC Project Lead as well! Patient retention rates in Canada continue to shine! We are happy to announce that Canada currently has 0 patients lost to follow up and 0 patients who have withdrawn consent! Thank you to all our sites for your continued efforts – this is a true testament of your commitment and excellence in patient care and follow up. Canada remains below the worldwide average for patients who have come off study drug and we hope to keep it that way! Please remember to review all of the options available with the patient prior to permanently discontinuing study drug and ensure that you have called the trial hotline to discuss all cases of patient drug discontinuations. If you would like further information on the EXSCEL trial, please contact Clinical Trials Project Lead Amanda Carapellucci at 1-800-707-9098 (ext. 2) or by email at amanda.carapellucci@ ualberta.ca or Diane Camara at 1-800-725-6585 or by email at dcamara@chrc.net. Exenatide Study of Cardiovascular Event Lowering Sponsored by Bristol-Myers Squibb, this trial is a pragmatic, long term, placebo- controlled, double-blinded trial which seeks to characterize the effects of exenatide once weekly on cardiovascular(CV) -related outcomes in patients with type 2 diabetes when added to the current usual care for glycemic control in a standard care setting. ClinicalTrials.gov Identifier: NCT01144338
SODIUM-HF SODIUM-HF is actively moving over a dozen sites through start-up! Thank you to all active sites for your efforts in getting started quickly and for working hard to recruit and enroll patients in this exciting trial! We have 4 sites activated, with a number of sites expected to be activated in the coming weeks and months. We will continue to work closely with each of your sites to ensure you are ready for activation as soon as possible. If your site is waiting for ethics approval or contract execution, this is a great time to tackle the regulatory documents and training pieces! Once these are complete it will be much easier and quicker to activate your site pending ethics approval and your fully executed contract. Please contact Melisa if you have questions about the training requirements for SODIUM or if the dietitian at your site has questions about the dietary intervention components. Congratulations to Dr. Toma, Elizabeth Grieve, and Sinead Feeney for enrolling their first patient on June 4, 2014! Congratulations to Dr. Jaffer and her team on being recently activated – we look forward to seeing your first patient enrolled!
on enrolling 3 patients since site activation on April 30, 2014! The Dietitians’ Working Group (DWG) is a unique opportunity for dietitians at active sites to ask questions and discuss any successful strategies or concerns related to patient enrollment and retention as well as tips for conducting the dietary intervention. Stay tuned for more details on the first DWG teleconference! SODIUM-HF is a unique heart failure trial and we are currently considering additional sites – if you would like to learn more about the trial or may be interested in participating as a site, please contact Clinical Trial Project Lead Melisa Spaling at 780-492-8476 or via email at mspaling@ualberta.ca Funded by the Canadian Institute of Health Research (CIHR), SODIUM-HF is a multicenter, randomized, open-label Study Of DIetary Intervention Under 100 MMOL in Heart Failure. ClinicalTrials.gov Identifier: NCT02012179
Congratulations to Dr. Ross, Lisa Garrard, and Margaret Brum Page 3
The Canadian Cardiac Chronicle - Volume 18
ODYSSEY OUTCOMES The ODYSSEY Outcomes trial is in full gear worldwide, with close to a quarter of the expected patients screened as of May! This is a great accomplishment that would not have been possible without the support of each and every one of our sites. Enrollment is moving along at a steady pace with over 4,600 patients randomized worldwide and over 60 in Canada. Over two thirds of our sites currently screening have now been activated under Amendment 6. With the increased flexibility this amendment provides, please make sure you are making full use of these changes at your site and seeking out all eligible patients! We encourage you to look back at your screening logs and to perform new database searches and chart reviews, as there are likely patients that you had previously excluded who may qualify with the changes brought about with this amendment! Remember that the global challenge set before all sites is to screen 5 patients within your first month of activation under Amendment 6! We would like to congratulate our top screening sites of 2014: • PI Dr. Jan Kornder – SC Dale Kastanis – 16 Patients Screened • PI Dr. Daniel Savard – SC Gina Vincelli – 11 Patients Screened • PI Dr. Manohara Senaratne – SC Bernadette Fernando – 9 Patients Screened • PI Dr. Bruce Sussex – SC Jill Cole – 6 Patients Screened • PI Dr. Simon Kouz – SC Madeleine Roy – 7 Patients Screened • PI Dr. Saul Vizel – SC Glorita Markov – 5 Patients Screened
Randomized • PI Dr. Tycho Vuurmans – SC Carol Marchand – 3 Patients Randomized Thank you for your commitment to the ODYSSEY Outcomes trial and for diligently continuing to search for eligible patients for this exciting trial. As mentioned in our last Canadian newsletter, we are excited to announce that CVC will be hosting a monthly ODYSSEY Outcomes Canadian Update WebEx! This time will be used to inform our sites of the status of the trial in Canada and Worldwide, go over FAQs, trial reminders, and any other pertinent topics. We encourage our ODYSSEY Outcomes sites to attend these sessions and look forward to your participation as well! The ODYSSEY Outcomes team wishes you safe and relaxing summer vacations. As you begin planning your trips and packing your bags, please ensure you notify your Project Lead of any office closures! We are still recruiting a few final sites for this study. Should you be interested in hearing more about ODYSSEY or have questions regarding the trial, please contact Clinical Trials Project Lead Amanda Carapellucci at 1-800-707-9098 (ext. 2) or by email at amanda.carapellucci@ualberta.ca or Paula Priest (ext. 9) or paula.priest@ualberta.ca.
And our top randomizing sites of 2014: • PI Dr. Jan Kornder – SC Lynn Breakwell/Dale Kastanis – 6 Patients Randomized • PI Dr. Manohara Senaratne – SC Bernadette Fernando – 6 Patients Randomized • PI Dr. Simon Kouz – SC Madeleine Roy – 5 Patients
Sponsored by Sanofi-aventis Recherche & Développement this is a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the effect of SAR236553/REGN727 on the occurrence of cardiovascular events in patients who have recently experienced an Acute Coronary Syndrome. ClinicalTrials.gov Identifier: NCT01663402
PROACT The Edmonton Emergency Medical Service paramedics have now enrolled two thirds of the required patients to complete this project. We appreciate their continued enthusiasm and commitment to this project and with their help look forward to completing this project in the fall of 2014 as planned. The PROACT Steering Committee met in May 2014 which was also the inaugural meeting with the Emergency Department Representatives. The Investigators of the study were recently awarded a grant from the Heart and Stroke Foundation of Canada, which will support completion of this project as planned. For further information please contact Paula Priest at 1-800707-9098 (ext 9) or email at paula.priest@ualberta.ca .
Providing Rapid Out of Hospital Acute Cardiovascular Treatment
PROACT
An Edmonton-region local initiative sponsored by the University Hospital Foundation and the Mazankowski Alberta Heart Institute. Additional support for point of care meters provided by Alere Inc. ClinicalTrials.gov Identifier: NCT01634425
Page 4
The Canadian Cardiac Chronicle - Volume 18
TECOS The slides which guide you through this process were sent out in April and presented in the end of study procedure webex sessions. They are a great step by step resource. If you cannot locate them or have any questions on how to complete data entry for the end of study visits please contact Tracy. As a reminder all data should be entered within a few days of the patient visit.
TECOS has now moved into the final phase and our sites are busy bringing all their patients in for the end of study visits. With a tight timeline to complete these visits we are pleased to see that our Canadian sites have again stepped up and quickly booked their patients in for these visits. If you have any patients who have needed to reschedule visits and will not meet the June 19 timeline for a visit please contact Tracy with the expected date of completion. While Canada has done a tremendous job keeping the withdrawn consent numbers low and maintained a status of no lost to follow up patients, we remain keen to ensure we have at minimum a vital status on all patients. With the efforts that have been implemented to date in the study and the recent communication to sites with patients who have withdrawn consent if you have any problems with the final follow up to obtain a vital status on these patients please contact Tracy. Every patient counts!
All sites should have received the Health Canada approval for amendment 3 and 4 recently. If you have not already sent us your ethics approval, protocol signature pages and documentation of training please submit them as soon as possible so we can proceed to officially activate your site on these amendments. This documentation can be submitted directly to Kalli Belseck at kalli@ualberta.ca. Many thanks to all of you for your hard work throughout this study. We are now in the home stretch and appreciate your continued dedication to complete all your visits including the post 28 day call. If you have any questions please don’t hesitate to contact Tracy Temple, Assistant Director-Clinical Trials at tracy.temple@ ualberta.ca or Kalli Belseck at kalli@ualberta.ca or by phone at 1-800-707-9098. Sponsored by Merck & Co. Inc., TECOS is a Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin in Patients with Type 2 Diabetes Mellitus and Inadequate Glycemic Control.
As you complete your study visits please remember to stay on top of your data entry. Remember the end of study visit needs to be entered on the next annual visit so you will need to navigate through the other visits to get to the next annual visit.
ClinicalTrials.gov Identifier: NCT00790205
AEGIS-I If you are a site with experience in phase 2 studies we are still interested in seeking a few additional sites to participate in this new phase 2b study investigating the safety and tolerability of multiple IV dose administration of CSL112 in patients with acute myocardial infarction with the intent to decrease recurrent cardiovascular events by reducing and/or stabilizing atherosclerotic plaque. CSL 112 is a novel formulation of apolipoprotein A-I (ApoA-I), purified from plasma and reconstituted to form high-density lipoprotein (HDL).
SODIUM-HF
We are pleased with the interest in the AEGIS-I study across Canada to date. The study is expected to start recruitment into the first phase of the study in June with the main study roll out planned for the fall.
For more information or if you are interested in hearing more about this study please contact Tracy Temple at 1-800-7079098 Option 5 or by email at tracy.temple@ualberta.ca.
We have been actively working through the final stages of site selection in Canada and plan to begin contract negotiations and ethics submissions in early June in anticipation of the study start up in the fall. We were pleased to receive Health Canada approval in May and can now move forward at an accelerated pace. Page 5
Sponsored by CSL Behring LLC, this study is a Phase 2b, multicenter, randomized,placebo-controlled, dose-ranging study to investigate the safety and tolerability of multiple dose administration of CSL112 in subjects with acute myocardial infarction.
The Canadian Cardiac Chronicle - Volume 18
GUIDE-IT Many thanks to all the Principal Investigators and Study Coordinators who attended the GUIDE-IT Investigator Meeting in Washington, D.C., on June 3-4. It was great to meet and discuss trial strategies and questions face-to-face! Congratulations to Dr. Ezekowitz and Quentin Kushnerik for winning the GUIDE-IT Trial Data Quality Award at the Investigator Meeting! All 6 Canadian sites are now active and enrolling subjects under Amendment 2! Amendment 2 has resulted in a large increase in enrollment, with a new trial record of 34 patients enrolled in the month of May. GUIDE-IT also achieved a trial milestone on May 1 with 25% of patients enrolled! Current enrollment now stands at 319 subjects (Canada = 32) with 43 active sites across North America. Congratulations to Dr. Toma, Cynthia Van Hoof & Elizabeth Grieve at St. Paul’s Hospital in Vancouver for enrolling 4 patients in 10 days! As part of the main GUIDE-IT trial, the ECHO substudy is now getting started and looking for additional sites to participate. The ECHO substudy consists of an echocardiogram at baseline and the 12-month visit (as well as prior to cardiac procedures, if possible to obtain). We are pleased to see the interest from our Canadian sites in this ECHO substudy. If you are participating the main study and your site is interested, please contact Melisa for additional substudy details.
Please remember to complete your screening logs and send them to CVC every week. These logs are helpful in assisting the operations team with identifying challenges in enrollment. When sites consistently submit screening logs on a weekly basis and have been consistent in enrolling subjects, we will no longer require you to submit these logs – so you can think of the screening logs as a bit of short term pain for long term gain! Thank you to all GUIDE-IT sites for your commitment to this important heart failure study. We look forward to continued collaboration on this trial. For further information, please contact Clinical Trial Project Lead Melisa Spaling at mspaling@ualberta.ca or direct: 1-780492-8476. In collaboration with DCRI (Duke Clinical Research Institute) and Roche GUIDE-IT is a prospective, randomized 1:1, multi-centre clinical trial GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure ClinicalTrials.gov Identifier: NCT01685840
BLAST-AHF BLAST-AHF is a fast-paced Phase IIb trial that is just getting started – six sites across Canada have been invited to participate and are busy reviewing regulatory documents and preparing ethics submissions. We anticipate quick site start-up in this trial with the goal of activating sites within a few months of receiving a complete regulatory package. If you are a participating site, thank you for your hard work so far and we look forward to our continued collaboration to make this trial a great success.
If you are interested in further information about BLAST-AHF or becoming a site for this study, please contact Clinical Trial Project Lead Melisa Spaling at 780-492-8476 or via email at mspaling@ualberta.ca
The BLAST trial plans to enroll up to 500 adult subjects, across 80 sites globally, to evaluate the safety and efficacy of TRV027 on symptoms of acute decompensated heart failure when administered in addition to standard of care. Page 6
Sponsored by Trevena Inc., BLASTAHF is A Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Explore the Efficacy of TRV027 in Patients Hospitalized for Acute Decompensated Heart Failure. ClinicalTrials.gov Identifier: NCT01966601
The Canadian Cardiac Chronicle - Volume 18
IMPROVE-IT
It’s really happening now! The IMPROVE IT study is ending. The end of study (EOS) visits began for all patients enrolled in IMPROVE IT on Thursday May 1, 2014 and continue through June 30, 2014. Detailed guidelines for completing final visits (Memo #411) were sent to sites on March 26, 2014. On March 31, 2014, the eCRF guidelines for completing final visits were also sent to the sites. At these visits, central labs are to be collected for all patients (whether they were on or off study drug). COM (completion) labels were sent to sites in April. If these were not received at your site, you should (1) take another label set for the same subject; (2) Cross out the visit name on the labels and write “COM” instead. Also write all subject/visit information clearly on the packing slip that is shipped with the samples. Now that we are in the EOS phase of the trial, it is crucial that all data is entered into Inform within 1 business day after a visit has occurred. The reason for this is so that data management can clean the data (i.e., query for any discrepancies) within 2 weeks after the data has been entered. If sites are late entering their data, then data management will be late in cleaning the data. To that end, CVC has been emailing sites each week notifying them of their current data status. Congratulations go out to the following sites whose data was ALL CLEAN (that is, no late, no missing, no queried data) as of May 23, 2014: • • • • • •
PI - Dr. Cheung & SC - Tracy Cleveland PI - Dr. Wong & SC - Roy-Anne Poirier PI - Dr. Doucet & SC - Martine Beaudry and France Paquette PI - Dr. Huynh & SC - Barbara St. Jacques PI - Dr. Kokis & SC - Carole Lemay PI - Dr. Theroux & SC’s - Josee Morrissette and Karine Deschenes • PI - Dr. Clarke & SC - Sharon Slipp • PI - Dr. Pallie & SC - Sheila Krekorian • PI - Dr. Grondin & SC - Noella Bilodeau
site has not yet received this IB, please notify CVC asap, as it needs to be submitted to your REB. Please forward a copy of your REB acknowledgement letter to CVC. To formally thank IMPROVE IT subjects for their time and commitment to the study over the last several years, a Thank-You card was created (Memo #413A) and sent to sites on May 2, 2014. Once REB approval has been obtained, sites may complete and submit the Email Order form that was provided as part of Memo #413A. These cards will then be sent to the sites, so that they may be mailed or given to patients on/after their EOS visits. As a reminder, 3 Field Communication Memos were sent to sites on April 16, 2014. Sites were to acknowledge these memos by signing them, and returning a copy to CVC (filing the original in their study binder). These memos pertain to lot numbers of study drug, and the sponsor required that these memos be filed at all sites. If you have not completed this task, please do so now. CEC Adjudicated Events – please remember to submit any outstanding (de-identified) source documents to the TIMI CEC at improveitcec@partners.org . For further information, please contact Clinical Trial Project Lead, Jodi Parrotta at 1-800-707-9098, ext. 3 or by email at jodi. parrotta@ualberta.ca . IMProved Reduction of Outcomes: Vytorin Efficacy International Trial Sponsored by Merck & Co. Inc (previously ., Schering- Plough Research Institute) this trial is a multicenter, double-blind, randomized study to establish the clinical benefit and safety of Vytorin (ezetimibe/simvastatin Tablet) vs. simvastatin monotherapy in high-risk patients presenting with acute coronary syndrome. ClinicalTrials.gov Identifier: NCT00202878
Keep up the GREAT work!! A hard copy and a CD of the updated Investigator’s Brochure Version #11 (Memo #412) was sent to all sites at the end of April, and should have been received by May 5, 2014. If your
Page 7
The Canadian Cardiac Chronicle - Volume 18
REGULATE-PCI The study is well underway with over 2500 patients enrolled at more than 300 sites in 16 countries across North America and Europe. In Canada we have over 200 patients enrolled from 10 sites as of June 5, 2014: • Dr. Cantor (Newmarket, ON) – 104 patients (in 9 months) • Dr. Charbonneau (Calgary, AB) – 38 patients (in 4 months) • Dr. Vijayaraghavan (Scarborough, ON) – 17 patients (in 3 months) • Dr. Cheung (Edmonton, AB) – 13 patients (in 2 months) • Dr. Mehta (Hamilton, ON) – 9 patients (in 4 months) • Dr. Fung (Vancouver, BC) – 8 patients (in 6 months) • Dr. Vo (Winnipeg, MB) – 8 patients (in 5 months) • Dr. McPherson (St. John’s, NFLD) – 8 patients (in 1 month) • Dr. Della Siega (Victoria, BC) – 4 patients (in 2 months) • Dr. Billingsley (Thunder Bay, ON) – 4 patients (in 1 month) We look forward to having the following four sites recruit their first patient in the coming weeks: • • • •
Dr. Boone (Vancouver, BC) Dr. Mansour (Montreal, QC) Dr. Philipp (New Westminster, BC) Dr. Welsh (Edmonton, AB)
Dr. Cantor’s site continues to excel! They remain the highest enroller in Canada, and hold the title of 3rd highest enroller globally. (FYI, the #1 and #2 sites are in the US, with 263 and 109 patients, respectively.) We continue to work on study start-up activities with the remaining 4 sites, and look forward to getting them activated in the next few weeks. As of June 10, 2014, 12 sites have been activated on Amendment 1.1 (version 2.1). Sites will receive an email from CVC when
they are approved to implement this amendment. For those who were already trained on the original protocol, training materials specific to Amendment 1.1 were sent to sites on April 24, 2014. For those who have not received any protocol training, a new training session, which included Amendment 1.1, was presented via webex on May 15, 2014. Materials from this session were sent to sites on May 23, 2014, and included the link to the recording of this webex, as well as a copy of the slides that were presented. An attestation can be signed; and the site’s training log can be updated accordingly. After reviewing the safety data on the first 1000 patients, the DSMB’s decision was to have the trial continue per the protocol. This also opened the study to all 3 subgroups. Thank you for all of your work in keeping the database as complete and clean as possible for this DSMB meeting. The next DSMB meeting will occur this summer when they look at the data from the first 25% of patients (~3300). Study Newsletter Issue #7 went out to sites on April 30, 2014. Thanks to all of you for attending the monthly study coordinator calls. The next SC call will be hosted by CVC. Stay tuned for further details! For further information, or if you are interested in participating, please contact Clinical Trial Project Lead, Jodi Parrotta at 1-800707-9098, ext. 3 or by email at jodi.parrotta@ualberta.ca. Sponsored by Regado Biosciences Inc. this is a randomized, open-label, multi-center, active-controlled, parallel group study to determine the efficacy and safety of the REG1 Anticoagulation System Compared to Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention Clinical trials.gov Identifier: NCT01848106
Page 8
The Canadian Cardiac Chronicle - Volume 18
Beyond 2000
Learning Objectives
After attending this symposium participants will be able to: 1. Identify the 10 Most Important ACS Advances in the last 20 years. 2. Recognize and avoid common mistakes in ACS management. 3. Apply recent data on STEMI care to current management strategies. 4. Make more informed choices on the use of antiplatelet and anticoagulant therapy. 5. Recognize residual risk and the need to account for the special challenges imposed by diabetes and dyslipidemia. 6. Develop strategies to overcome the risk-‐treatment paradox.
Agenda | 20th Anniversary Program Sunday, October 26, 2014
Chair: Paul W. Armstrong, MD Co-‐Chair: Anthony Fung, MD 06:55 Welcome & Overview
Paul W. Armstrong, MD
07:00
Robert Harrington, MD
07:20
07:40
The 10 Most Important ACS Advances in the Last 20 Years
The 10 Most Important Mistakes in ACS Care in the Last 20 Years
STEMI Care 2014 at the Crossroads: Taking the Right Road
08:00
Illuminating the Cloudy Path of Antiplatelet/Anticoagulant Therapy Post ACS: How Much of What, for Whom and for How Long?
08:20
Case Presentations
09:00
Overcoming the Risk-‐Treatment Paradox in Non-‐STE: It’s Time!
09:20
Residual Risk Post ACS: Facing the Diabetes/Metabolic Syndrome Challenge
Break
The Cholesterol Conundrum Post ACS: Who to Treat, When, How and to What End?
10:00
Eric Cohen, MD
University of Toronto Toronto, ON
Robert Welsh, MD
University of Alberta Edmonton, AB
Shaun Goodman, MD University of Toronto Toronto, ON Surrey Memorial Hospital Surrey, BC
09:40
Stanford University Stanford, CA
Richard Bon, MD
08:40
University of Alberta Edmonton, AB
Conclude
Page 9
Christopher Granger, MD
Duke University Medical Center Durham, NC
Irene Hramiak, MD University of Western Ontario London, ON
John Mancini, MD University of British Columbia Vancouver, BC
The Canadian Cardiac Chronicle - Volume 18
Insights from the CVC Clinical Trial Research Colloquium March 2014
Originally highlighted in the Spring 2014 Chronicle the Canadian VIGOUR Centre (CVC) hosted a roundtable discussion in Banff, Alberta which involved 11 investigators and 12 study coordinators from 13 clinical trial sites across Canada, as well as the supporting sponsor representatives. A total of 16 sites completed a very detailed survey which asked 75 questions ranging from how long it takes to start up a trial, to ethics approvals and other key questions of how we can best optimize a clinical trial site, the academic research organization such as ourselves and the sponsors’ interaction throughout the trial. We had a 100% response rate to the survey and the overall feedback from all involved was this was a worthwhile exercise. Not only did we learn more about best practices across the country, we learned more about our own clinical trial sites and how we can do things better to improve clinical research. To date, sites that participated received their own data back in the form of a report card with comparisons to the overall group.
experienced sites that contract negotiation and consent review/ ethics approvals were the most significant barriers to a quick startup both at the site level and the ARO or sponsor level. Some (but not all) noted that a master service agreement between the site and a sponsor helped speed up the process.
Figure 1 - Sites Average Time to Activation 9-12 months 4-6 months 2-4 months 1-2 months 0
20
40
60
80
100
Percent
We have categorized and summarized some of the key findings from the survey below. 1. Sites: We had coast-to-coast representation of in-hospital and outpatient-based research in both cardiology and cardiovascular risk in diabetes. Most sites had been doing clinical research for over 10 years. Many of the Study Coordinators are running between 3 to 4 projects at any one time, and it was nice to see that many sites have administrative support. 2. Startup: Interestingly, when we asked the question about the sites average time from receiving all study documents to site activation and subsequently asked what was the quickest timeframe the site had completed startup, we saw a dramatic difference in responses (Figure 1: Average time to activation; Figure 2: Fastest time to activation). This generated some good discussion during the meeting, as it demonstrates that quick start up is possible and will enable us to deploy strategies that allow a quicker start up. It will come as no surprise to
Figure 2 - Sites Quickest Time to Activation 9-12 months 4-6 months 2-4 months 1-2 months
Page 10
0
20
40
60 Percent
80
100
The Canadian Cardiac Chronicle - Volume 18
3. Communication: There is no question and almost unanimous support that sites prefer e-mail for communication regarding trial updates, and found enrollment updates, information regarding the study drug or data status, and study supplies very valuable. Findings relating to an audit or advance notice of changes to the study were also seen as useful for the participating sites. While we have seen an increase in the use of electronic study portals it was interesting to note that these web-based trial portals were not preferred for trial updates although they were felt to be a useful repository of information for relevant study documents. 4. Training: The majority of sites preferred face-to-face investigator meetings. This is an important factor for us to consider as many trials are moving to web-based training, and with increasing trial complexity including the delivery of study drug we need continue to advocate for the face to face meetings and ensure presence of not only our study coordinators but investigators as well. 5. Enrollment: In Canada, we have traditionally made a good contribution to trial recruitment and often exceed expectations. Aiming to maximize our recruitment time in studies, we looked at average times from activation to recruitment of a first patient and again asked the question about the sites quickest time to recruit based on previous experience. While the average time was 2-4 weeks we again saw that sites were capable of doing this in less than 1 week. As we put this question under the microscope, there were many strategies that contributed to this success but there was an overwhelming majority who said that involved Investigators, a protocol that fits real world clinical practice, and patient population that fits the protocol (i.e. there are real-world patients being tested) were the key features to successful site level recruitment.
Figure 3 - Sites Average Time to 1st Patient >2 months 1-2 months 2-4 weeks 1-2 weeks <1 week 0
20
40
60 Percent
80
100
Figure 4 - Sites Quickest Time to 1st Patient >2 months 1-2 months 2-4 weeks 1-2 weeks <1 week 0
20
40
60
80
100
Percent
6. Feasibility: We were very pleased to see that the primary reason for participating in a clinical trial is â&#x20AC;&#x153;clinical relevanceâ&#x20AC;?. This speaks to our mutual goals of improving cardiovascular health for our patients. Other deciding factors included staffing and resources, whether or not the inclusion or exclusion criteria fit the practice environment or the clinical setting and importantly, who is the sponsor or ARO. With representation of sites from multiple specialties including ACS, heart failure, and diabetes, this was also a unique opportunity to have 3 lead Investigators (Dr. Jan Kornder, Dr. Shelley Zieroth and Dr. Irene Hramiak) provide their perspective on unmet needs, looking at whether all trials are the same, and explore what the value add is with regard to the Canadian contribution. Where do we go from here? We appreciate the support from our sponsors Amgen, Merck Canada, Sanofi-aventis, and AstraZeneca to have the opportunity to host this colloquium. This was an excellent forum for sites, sponsors and CVC to come together with the goal of generating productive dialogue to identify key issues impeding clinical trial involvement in Canada and to develop strategies to address them. Within CVC we are actively developing creative solutions to the problems identified at the colloquium. We are committed to improving the overall clinical research experience and will work collaboratively on solutions that will be beneficial overall to our sites. We plan to have subsequent meaningful meetings similar to the one we had in Banff in March 2014 with initial plans to have another clinical trial colloquium in Banff in 2015, linked to the ACC Rockies meeting led by Dr. Robert Welsh. We are also exploring ways to reach out to our other 400+ Investigators and sites with whom we are engaged with clinical research.
Page 11
The Canadian Cardiac Chronicle - Volume 18
Publications Armstrong PW, Van de Werf FV. No STEMI Left Behind (Invited Editorial re 2013 STEMI Consensus Statement in India) JAPI. 2014; 62:461-462. http://www.japi. org/june_2014/01_editorial_no_stemi_left.pdf Bainey KR, Armstrong PW. Clinical perspectives on reperfusion injury in acute myocardial infarction. Am Heart J. 2014 May;167(5):637-45. http://www.ncbi. nlm.nih.gov/pubmed/24766972 Bainey KR, Armstrong PW, Fonarow GC, Cannon CP, Hernandez AF, Peterson ED, Peacock WF, Laskey WK, Zhao X, Schwamm LH, Bhatt DL. Use of renin-angiotensin system blockers in acute coronary syndromes: findings from Get with the Guidelines-Coronary Artery Disease Program. Circ Cardiovasc Qual Outcomes. 2014 Mar;7(2):227-35. http://www.ncbi.nlm.nih.gov/pubmed/24569634 Bainey KR, Mehta SR, Lai T, Welsh RC. Complete vs culprit-only revascularization for patients with multivessel disease undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review and meta-analysis. Am Heart J. 2014 Jan;167(1):1-14.e2. http://www.ncbi.nlm.nih.gov/pubmed/24332136
acute heart failure: Insights from the ASCEND-HF trial. J Card Fail. 2014 May;20(5):319-26. http://www.ncbi.nlm.nih.gov/pubmed/24530944
Bao MH, Armstrong PW, Zheng Y, Westerhout CM, Siha H, Welsh RC. The Prognostic Relationship of QT interval and dispersion in patients with acute ST elevation myocardial infarction. Journal of Experimental & Clinical Cardiology. 2014;20(1):1464-1489. http://cardiologyacademicpress.com/?p=19771
Lyons KJ, Ezekowitz JA, Liu W, McAlister FA, Kaul P. Mortality Outcomes Among Status Aboriginals and Caucasians with Heart Failure. Can J Cardiol 2014 Jun;30(6):619-626. http://www.ncbi.nlm.nih.gov/pubmed/24882532
Goodman SG, Wojdyla DM, Piccini JP, White HD, Paolini JF, Nessel CC, Berkowitz SD, Mahaffey KW, Patel MR, Sherwood MW, Becker RC, Halperin JL, Hacke W, Singer DE, Hankey GJ, Breithardt G, Fox KAA, Califf RM, for the ROCKET AF Investigators. Factors associated with major bleeding events: Insights from the rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for Prevention Of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). J Am Coll Cardiol. 2014;63(9):891-900. http://www.ncbi.nlm.nih. gov/pubmed/24315894 Grima DT, Brown ST, Kamboj L, Bainey KR, Goeree R, Oh P, Ramanathan K, Goodman SG. Cost-effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes in Canada. Clinicoecon Outcomes Res. 2014 Jan 24;6:49-62. http://www.ncbi.nlm.nih.gov/pubmed/24493930 Kalogeropoulos AP, Tang WH, Hsu A, Felker GM, Hernandez AF, Troughton RW, Voors AA, Anker SD, Metra M, McMurray JJ, Massie BM, Ezekowitz JA, Califf RM, O’Connor CM, Starling RC, Butler J. High sensitivity C-reactive protein in
Lee DS, Ezekowitz JA. Risk stratification in acute heart failure. Can J Cardiol. 2014 Mar;30(3):312-319. http://www.ncbi.nlm.nih.gov/pubmed/24565256
Mahaffey KW, Stevens SR, White HD, Nessel CC, Goodman SG, Piccini JP, Patel MR, Becker RC, Halperin JL, Hacke W, Singer DE, Hankey GJ, Califf RM, Fox KA, Breithardt G; for the ROCKET AF Investigators. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial. Eur Heart J. 2014 Jan 21;35(4):23341. http://www.ncbi.nlm.nih.gov/pubmed/24132190 van Diepen S, Chen AY, Wang T, Alexander K, Ezekowitz JA, Peterson ED, Roe MT. Influence of heart failure symptoms and ejection fraction on short- and long-term outcomes for older patients with non-st-segment elevation myocardial infarction. Am Heart J 2014;167(2):267-273. http://www.ncbi.nlm. nih.gov/pubmed/24439989 Wang TS, Hellkamp AS, Patel CB, Ezekowitz JA, Fonarow GC, Hernandez AF. Representativeness of RELAX-AHF Clinical Trial Population in Acute Heart Failure. Circ Cardiovasc Qual Outcomes. 2014 Mar 1;7(2):259-68. http://www. ncbi.nlm.nih.gov/pubmed/24594552
Publication Information This newsletter is published periodically as a service to Canadian investigational sites. The purpose is to provide information of interest to individuals involved in cardiovascular clinical trials managed by the Canadian VIGOUR Centre, University of Alberta in Edmonton, Alberta, Canada. The VIGOUR (Virtual CoordInating Centre for Global COllaborative CardiovascUlar Research) group is an international academic group committed to advancing cardiovascular medicine and enhancing patient care worldwide. Its membership includes: the Canadian VIGOUR Centre (CVC), University of Alberta, Edmonton, Alberta, Canada; Green Lane Coordinating Centre, Auckland, New Zealand; National Health & Medical Research Council – Clinical Trials Centre, Sydney, Australia; Flinders Medical Centre, Bedford Park, Australia; Duke Clinical Research Institute (DCRI), Duke University, Durham, NC, USA; Leuven Coordinating Centre, University Hospital Gasthuisberg, Leuven, Belgium; ECLA, Rosario, Argentina, South America; TANGO, Buenos Aires, Argentina, South America; Uppsala Clinical Research Centre, Uppsala, Sweden
Address for Inquiries: 2-132 Li Ka Shing Centre for Health Research Innovation University of Alberta, Edmonton, AB, Canada, T6G 2E1 Phone: 1-800-707-9098, Fax: (780) 492-0613 www.vigour.ualberta.ca
CVC gratefully acknowledges our sponsors and the funding support provided by: Alere Inc. Amgen AstraZeneca Boehringer Ingelheim Bristol-Myers Squibb CSL Behring LLC Hoffmann-La Roche Merck & Co., Inc.
Regado Biosciences Inc. Roche Diagnostics Operations Inc. Sanofi-aventis Recherche & Développement Trevena Inc. Canadian Institute of Health Research Mazankowski Alberta Heart Institute University Hospital Foundation
Canadian Cardiac Chronicle Editorial Board: Paul W. Armstrong Kalli Belseck Amanda Carapellucci Justin Ezekowitz
Page 12
Halina Nawrocki Jodi Parrotta Dianne Payeur Carla Price
Paula Priest Ellen Pyear Melisa Spaling Tracy Temple