Science Platforms

Clinical Trials and Shared Platforms

This platform supports pilot clinical trials that will inform the conduct of full randomized controlled trials. Pilot trials will evaluate the feasibility of recruitment and study procedures, and will inform sample size calculation and study logistics. Conducting pilot trials will increase the ability to secure large-scale funding for collaborative multicenter trials. To this aim, we have launched our third Call for Proposals! Details can be found at this link: CanVECTOR Pilot Trials Funding 2018.

This platform will also develop shared research platforms to reduce barriers for thrombosis clinical research centres and to increase efficiency for the centres that are coordinating multi-centre studies, particularly clinical trials. This will be achieved by standardizing methods of communication, including electronic data capture; standard operating procedures; operation manuals; outcome event adjudication; and common informed consent language, where feasible. We will assemble and share information on best-practices for the conduct of multi-centre trials. The shared platforms will build and sustain the infrastructure and transdisciplinary collaborations required to conduct and monitor large scale multicentre clinical trials with high efficiency and minimal duplication of tasks and services.

The Team

Platform Co-Leads

Clive Kearon (Hamilton, ON)
Grégoire Le Gal (Ottawa, ON)

Working Group

Network members are invited to participate in project-specific working groups according to their interests. Input from a variety of participants including investigators, statisticians, computer programmers, trialists, multi-centre research coordinators, and local research coordinators will ensure that the shared research platforms are developed to best meet the needs of the users.

The Projects

1. Pilot Trial: Comparison of Bleeding Risk Between Rivaroxaban and Apixaban (COBRRA)

Principal Investigator (junior)

Dr. Lana Castellucci (Ottawa)

Principal Investigator (senior)

Dr. Marc Rodger (Ottawa)

Lead Pilot Site Investigators

Hamilton - Dr. Kerstin de Wit
Edmonton - Dr. Cynthia Wu
Sherbrooke - Dr. Genevieve Le Templier

Recently developed new oral anticoagulants (OAC) overcome some of the limitations of established therapy with vitamin K antagonists (VKA) and low-molecular-weight heparin (LMWH) for treatment of acute venous thromboembolism (VTE), due to ease of administration and more predictable pharmacokinetic properties. Many clinical questions about the new OAC remain unanswered because there have not been direct head-to-head comparison trials. For example, although studies have shown that rivaroxaban and apixaban are at least as effective and safe as LMWH and VKA, meta-analyses suggest that apixaban may be associated with lower bleeding risk. Concerns about the potential impact of medication non-adherence have been raised. Compliance with twice daily medications (e.g. apixaban) is often worse than once daily medications (e.g. rivaroxaban). Both of these medications are approved by Health Canada for treatment of VTE yet there is genuine uncertainty about which of the two direct OAC confer the best risk-to-benefit ratio.

This is a multi-centre, prospective randomized open blinded end-point (PROBE) trial assessing clinical feasibility for a larger multi-centred trial comparing bleeding outcomes using apixaban versus rivaroxaban for treatment of acute VTE. The primary objective of the study is to determine if it is feasible to conduct a large randomized multi-centre trial comparing apixaban to rivaroxaban for the treatment of acute VTE. The secondary objectives are to assess safety and superiority of apixaban versus rivaroxaban.

This pilot trial has been completed. It demonstrated feasibility and informed the procedures of the full clinical trial which is funded by a Project Grant from the Canadian Institutes of Health Research (CIHR).

For more details on the full clinical trial see ClinicalTrials.gov: NCT03266783

For more details on the pilot trial see ClinicalTrials.gov: NCT02559856

2. Pilot Trial: Assessing the feasibility of a randomized controlled trial evaluating low-molecular-weight-heparin and aspirin versus aspirin alone in women with antiphospholipid syndrome and pregnancy loss (APPLE)

Principal Investigator (fellow)

Dr. Leslie Skeith (Ottawa)

Co-Principal Investigator (supervisor)

Dr. Marc Rodger (Ottawa)

Co-Investigator

Dr. Shannon Bates (Hamilton)

Women with antiphospholipid syndrome (APS) are at increased risk of pregnancy loss compared to the general population. There is poor-quality evidence supporting the use of prophylactic low-molecular weight heparin (LMWH) and aspirin (ASA) in pregnancy for women with APS and past pregnancy loss. Downsides of LMWH include burden of injections (up to 400 injections per pregnancy), cost (more than $4,000 per pregnancy) and side effects of LMWH. When uncertainty exists in pregnancy, health care providers and patients often err on the side of treatment in hopes of preventing complications. Our goal is to minimize uncertainty, to provide clear recommendation to women with APS and pregnancy loss based on high-quality evidence.

This APPLE pilot trial will be conducted at two centers (Ottawa and Hamilton) to determine if it is feasible to conduct the multicenter randomized APPLE trial in women with APS and previous pregnancy loss. We estimate that the multicenter trial will target 40 centers and will be completed over 5 years to answer the question of whether the use of prophylactic LMWH and ASA improves the livebirth rate when compared to ASA alone. The APPLE trial will be considered feasible if the APPLE pilot trial demonstrates that recruitment rates average, at a minimum, 1 patient every 2 months per site.

This pilot trial is recruiting participants. For more details see ClinicalTrials.gov: NCT03100123

3. Pilot Study: Optimizing the Diagnosis of Heparin Induced Thrombocytopenia Using Quantified Anti-Platelet Factor 4 Immunological Testing: A Prospective Cohort Study

Principal Investigator (junior)

Dr. Lisa Duffett (Ottawa)

Co-Investigators

Dr. Esteban Gandara (Ottawa)
Dr. Rick Ikesaka (Fellow, Ottawa)
Dr. Gregoire Le Gal (Ottawa)
Dr. Sudeep Shivakumar (Halifax)

This is a prospective cohort study exploring a novel diagnostic approach to Heparin Induced Thrombocytopenia (HIT) using a combination of pretest probability assessment and quantitative interpretation of the anti-platelet factor 4 Immunological assay (anti-PF4). Patients with a clinical suspicion of HIT will follow the study-specific diagnostic algorithm. The results using the study algorithm will be compared to the Serotonin Release Assay (SRA) gold standard test. Pre-specified criteria will be used to determine if the study algorithm is a safe approach that should be evaluated in a larger randomized controlled trial (RCT). The cohort study will also inform feasibility and recruitment barriers for the larger RCT study. 

This study is not yet recruiting participants. For more details see ClinicalTrials.gov: NCT03148912

4. Pilot Study: Tumour-educated platelets to detect cancer in patients with unprovoked venous thromboembolism (PLATO)

Principal Investigator (PhD student)

Noémie Kraaijpoel

 Canadian Co- Investigator (supervisor)

Marc Carrier (Ottawa)

The PLATO pilot study aims to evaluate the feasibility of participating in an INVENT-VTE multi-center, multi-national, prospective, observational cohort study assessing the diagnostic accuracy of platelet mRNA profiling for occult cancer in the setting of venous thromboembolism (VTE). The results of this cohort study will inform and help to design a large multinational randomized controlled trial assessing the efficacy of platelet mRNA to detect occult cancer in patients with unprovoked VTE.

 In the current study, patients of 40 years or older with a first episode of unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) will be eligible. Informed consent will be obtained within 10 days of the index unprovoked VTE and blood will be drawn and stored until central platelet mRNA profiling. Patients will undergo standard-of-care limited screening for cancer and be followed for 12 months.The pilot study will assess feasibility in two CanVECTOR sites (Ottawa, London) and the data will enable leverage of additional peer-reviewed funds for participation in the full-scale study and future randomized controlled trial. CanVECTOR Pilot Trial Funding will allow for the recruitment of 50 patients (Ottawa n=25; London n=25) over 6 months (primary objective). Secondary outcomes measures include evaluation of compliance to study procedures and follow-up visits and reasons for non-participation. The primary objective of the full-scale study is to evaluate the sensitivity of platelet mRNA profiling in detecting occult cancer.

This pilot trial is recruiting participants. For more details see ClinicalTrials.gov:  NCT02739867

5. Pilot Trial: A pilot study assessing the feasibility of a randomized controlled trial investigating primary thromboprophylaxis with rivaroxaban in patients with malignancy and central venous catheters (TRIM-Line )

Principal Investigator (fellow)

Dr. Rick Ikesaka (Ottawa)

Co-Principal Investigator (supervisor)

Dr. Marc Carrier (Ottawa)

Co-Investigators

Sudeep Shivakumar (Halifax) Dalhousie University
Cynthia Wu (Edmonton)

The TRIM-Line pilot trial will assess the feasibility of conducting a full-scale, multicentre, randomized controlled trial evaluating a prophylactic dose of direct oral anticoagulant therapy, rivaroxaban, for the primary prevention of venous thromboembolism (VTE) in cancer patients with a central venous catheter (CVC). The pilot trial will be conducted at 3 Canadian centres: Ottawa, Halifax and Edmonton, over a 6-month span. The primary feasibility outcome will be the monthly recruitment rate. The target recruitment will be a total of 10 participants per month with site goals of 4-5 monthly enrollments at each of the established centres of Ottawa and Halifax and 1-2 per month at the emerging centre of Edmonton. Secondary feasibility outcomes and those in keeping with anticipated outcomes for the full-scale trial will also be collected.

6. Pilot Trial: Apixaban versus low molecular weight heparin for treatment of catheter related Thrombosis in Cancer patients. A pilot study to assess feasibility of a randomized controlled trial (ALaCaRT)

Principal Investigator (fellow)

Dr. Deepa Suryanarayan (Calgary)

Co-Investigators

Eddy Lang (Calgary)
Marc Carrier (Ottawa)
Dwip Prajapati (Calgary)
Steve Doucette (Ottawa)

Catheter related thrombosis (CRT) in cancer can result in treatment interruption, failure of the catheter, risk of pulmonary embolism (PE), post thrombotic syndrome and risk of infection. There currently exists clinical equipoise regarding optimal management of CRT in cancer with a need for a randomized clinical trial to evaluate safety and efficacy of direct oral anticoagulant agents (DOACs) in comparison to low molecular weight heparin (LMWH) in this patient population.   ALaCaRT is an open label pilot study to assess feasibility of a multicenter randomized controlled trial comparing Apixaban and current standard of care with LMWH in cancer patients diagnosed with CRT. This study design will help us assess the safety of Apixaban in comparison to LMWH, assess the recruitment potential, evaluate feasibility of collaboration and coordination for a larger RCT.

7. Modular Trial and Data Management Templates

Web-based platforms are rapidly replacing paper-based case report forms (CRF). These systems integrate electronic data capture (EDC) and trial management functions such as tracking essential documents, payments, inventory of study drug, and biological samples. These platforms also integrate quality assurance throughout the study (eligibility checks; required fields; real-time edits; internal data validation and monitoring).

8. CanVECTOR Web-based Adjudication Platform

Currently, adjudication is done with paper-based forms at face-to-face meetings; this is time consuming, inconvenient, and reduces independent evaluation by dual adjudicators. We have developed and are currently testing a web-based adjudication platform that will allow adjudicators to do this work on their own time, more efficiently, and with a lower potential for biased interpretation.