|Project Title||PI||Description||Research Theme||Date of Completion||Publication Link|
|FIBrinogen REplenishment in Surgery (FIBRES)||Dr. Keyvan Karkouti & Dr. Jeannie Callum||This is a pragmatic, prospective, multi-center, randomized, active-control, single-blinded, non-inferiority phase 3 trial in adult cardiac surgical patients. Up to 12 Canadian hospitals will participate, and the trial will require up to 2 years for patient recruitment.|
Twelve-hundred bleeding adult cardiac surgical patients who require fibrinogen supplementation due to acquired hypofibrinogenemia after CPB will be included. Patients will be randomized to receive equivalent doses of either fibrinogen concentrate (Octafibrin) or cryoprecipitate when the blood bank receives the first order for fibrinogen supplementation and deems it to be in accordance with accepted clinical standards. Thereafter, patients will be treated according to their assigned group each time fibrinogen supplementation is ordered during the treatment period (24 hours after termination of CPB). No other aspects of care will be modified.
The primary efficacy outcome will be the number of Allogeneic blood products (ABP) (red blood cells [RBCs], pooled or apheresis platelets, and plasma) administered during the first 24 hours after termination of CPB. Safety outcomes will be measured for the first 28 days after surgery, which is the duration of participation of each patient in the trial. Comparisons will be by intention-to-treat (ITT) (primary) and per-protocol (PP) analysis. One interim analysis will be conducted after 600 patients have been treated to determine whether the study should be terminated for safety reasons, demonstrated non-inferiority or futility reasons.
|Utilization||October 2019||View Publication|
|Isoagglutinins in the Development of IVIG-associated Hemolysis||Dr. Don Branch & Dr. Jacob Pendergrast||Patients at high risk of IVIG-associated hemolysis (defined as receipt of a 28-day cumulative dose of ≥ 2 g/kg, adjusted for ideal body weight, and non-O blood group) will be prospectively monitored using a standardized protocol for signs of hemolysis, and will be undergo additional testing for variables that have been hypothesized to increase the risk of hemolysis. The goal of the study is to define the incidence and dynamics of IVIG-mediated hemolysis and identify patient and product-related factors that may predict which patients are especially at risk.||Safety||May 2019||View Publication|
|Transfusion-Associated Circulatory Overload Best Eliminated With Lasix (TACO-BEL-1)||Dr. Jacob Pendergrast||Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-attributable morbidity and mortality. While diuretics are standard of care for treatment of heart failure, it is unclear whether they are safe and effective in preventing TACO. This is a pilot double-blinded placebo-controlled randomized controlled trial (RCT) to evaluate the feasibility of conducting a multicenter, randomized, placebo-controlled trial to assess the efficacy of pre-transfusion furosemide in preventing transfusion-associated circulatory overload (TACO) in hemodynamically stable inpatients aged 65 years or older receiving a single unit red blood cell transfusion. Nine months of enrollment were required for 80 patients to complete the study. Factors impacting accrual rate included fewer transfusions than expected meeting eligibility criteria and lower than anticipated consent rates. Protocol compliance was also below target due to missing nursing chart documentation of patient weight and/or fluid balance, and transfusion infusion time. Blinding was maintained throughout the study and treatment arms were well-balanced. A single case of TACO occurred in each arm, for an overall incidence of 2.5%. No differences observed in peritransfusion vital signs or B-natriuretic peptide. No furosemide toxicity observed.|
Conclusion: The study protocol successfully randomized 80 patients to pre-transfusion furosemide while maintaining blinded treatment allocation and outcome assessment. Modifications to trial design to improve feasibility have been identified and will inform the design of future studies.
|Safety||March 2019||View Publication|
|Cardiac Stress Biomarkers after Red Cell Transfusion in Patients at Higher Risk for Transfusion|
Associated Circulatory Overload: A Prospective Observational Study (TACO-BEL-2)
|Dr. Jeannie Callum & Dr. Christine Cserti||Background: Transfusion-associated circulatory overload (TACO) is a leading cause of serious reactions. Little is known regarding the value of cardiac biomarkers as a predictor of TACO, in differentiating TACO from other dyspneic reactions, or the optimal timing/thresholds. Methods: Prospective observational study of inpatients at higher risk for TACO (age>50) receiving 1 red cell unit. Cardiac biomarkers, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and high sensitivity troponin measured at baseline, 6-12 hours (except troponin), and 18-24 hours post-transfusion. Primary outcome: critical rise (-CR) in biomarkers (>1.5-fold rise and exceeding a threshold) at 18-24 hours. Results: 51 patientsanalyzed; 29% had pre-existing cardiovascular disease, 73% had ≥1 cardiac risk factors, and 50% took cardiac/antihypertensive therapies. No reactions observed; 8 (16%) developed rise in systolic pressure >30 mmHg and 4 (8%) reported dyspnea/cough. At baseline, BNP level was >100 ng/L in 59% and NTproBNP was >300pg/mL in 83%. 25% had a BNP-CR, 33% had a NT-proBNP-CR, and 2% had a troponin-CR at 18-24 hours. Overall, 38% had at least one biomarker-CR and NT-proBNP/BNP concordance was 84%. The highest biomarker yield was the NT-proBNP (>1.5 fold rise and >300 pg/mL) at 18-24 hours. Conclusions: In higher risk patients for TACO, baseline elevation in biomarkers is common and critical rises occur in a third. The optimal measurement interval as a surrogate marker for TACO is at 18-24 hours post-transfusion. Larger studies are needed to clarify the risk of TACO for a given pre-transfusion biomarker profile and the correlation between TACO and rise in biomarkers post-transfusion.||Safety||September 2018||View Publication|
|A feasibility study and a retrospective audit of diuretics for patients receiving blood transfusion at ten Canadian hospitals (TACO-BEL-3)||Dr. Jacob Pendergrast||Feasibility was not demonstrated within the two participating sites in TACO-BEL-1, primarily due to slower-than-expected enrollment. In the current study, we tested the feasibility of enrollment for a multi-site trial. For a baseline TACO risk of 3%, 2 600 participants would be required to detect a 40% relative risk reduction with 80% power and alpha of 0.05. This target could be achieved within 1 year at an average monthly enrollment rate of 217 patients. This study suggests that the 10 participating sites could achieve the enrollment target of 2600 patients in approximately 15 months; enrollment could be achieved within 1 year if the consent rate could be improved to 25%. The baseline incidence of TACO was slightly higher than anticipated, despite the inclusion of younger patients than was allowed in the pilot study.||Safety||March 2018||View Publication|
|Massive hemorrhage protocol||Dr. Katerina Pavenski||Determine the impact of a standardized provincial massive transfusion protocol on outcomes of patients with acute traumatic injury, with a utilization sub-study to determine effectiveness of protocol on preventing blood wastage.||Utilization||January 2019||View Publication|
|Impact of Transfusion Camp-1||Dr. Yulia Lin||The optimal method of providing transfusion medicine (TM) education has not been determined. Transfusion Camp was established in 2012 at the University of Toronto as a centrally-delivered TM education program for postgraduate trainees. The impact of Transfusion Camp on knowledge, attitudes and self-reported behavior was evaluated. Didactic lectures (delivered locally, by webinar or recorded) and locally facilitated team-based learning seminars were delivered over 5 days during the academic year to 8 sites: 7 in Canada and 1 in the United Kingdom. Knowledge assessment using a validated 20 question multiple choice exam was conducted pre- and post-Transfusion Camp. Attitudes and self-reported behavior were collected through survey.|
CONCLUSIONS: Transfusion Camp increased TM knowledge, fostered a positive attitude towards TM and enabled a self-reported positive impact on transfusion practice in postgraduate trainees. It is a novel and scalable approach to delivering TM education.
|Education||April 2019||View Publication|
|TESS Error System – Sample Collection and Handling Errors||Dr. Jeannie Callum & Dr. Christine Csert||Transfusion errors in Canada. The UofT QUEST investigators have received approval from the Public Health Agency of Canada to conduct an analysis to characterize the sample collection and handling errors that have occurred in Canada over the past 10 years (PI: Callum). Sunnybrook Health Sciences Centre is a sentinel site for transfusion error data collection as part of the Transfusion Error Surveillance System (TESS). In 2017, our research team has been requested to analyze the national data and submit to a peer reviewed journal. Our goal is to identify where, when and why these errors are occurring in hospitals and utilize this as a base to influence hospital policy and transfusion standards that relate to sample collection for transfusion compatibility testing. This will allow the UofT QUEST to identify frequent high risk errors and then develop and test innovative strategies to determine how best to prevent these errors. Indeed, Sunnybrook Health Sciences Centre is at the beginning of a phased rollout of bedside computer technology to facilitate error-free sample collection. If we can scientifically prove these innovative technologies improve safety we can lobby to ensure transfusion standards are modified to require accurate labelling strategies.||Safety||April 2018||View Publication|
|Yield of serologic investigations from transfusion reactions||Dr. Christine Cserti||Serologic testing (ST) of acute transfusion reactions examines for potentially accountable immune haemolytic incompatibility. At our institutions, ST applies to all|
reported reactions, with the exception of low-risk fevers (subclinical temperature ≤39⁰C) or uncomplicated allergic reactions. Compliance with these guidelines, and reaction-specific yields, are unknown. Such measures may reflect quality of practice and inform investigation algorithms.
Conclusion: Analysis of the performance and contextual yields of ST revealed product-specific hierarchies. A re-evaluation of traditional ST algorithms may reduce costs and allow reinvestment in other more informative reaction-specific assays.
|Utilization||August 2019||View Publication|
|Serology eModules Instruction||Dr. Jacob Pendergrast||Education||May 2019||View Publication|