|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.
|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.||Publication in progress|
|A Multifaceted Intervention to Optimize Red Blood Cell Transfusion Practice in Two Provinces (START)||Dr. Kathryn Webert & Dr. Jeannie Callum||People receive red blood cell (RBC) transfusions for many reasons including surgery, injury, cancer, bleeding and being treated for diseases of the blood. A RBC transfusion is the most common procedure performed in the hospitalized patient, with ten percent of hospitalized patients being transfused. The decision to transfuse RBCs is based on a number of factors such as the amount of hemoglobin in your blood, amount of blood loss, your clinical condition and whether you have heart disease. Often however, physicians transfuse patients based solely on the laboratory test results, without taking into account individual patient factors. There is a growing awareness that RBC transfusion is an overused treatment, with as many as 1 in 5 Ontario transfusions being unnecessary. Unnecessary transfusions result in poor patient outcomes and increased hospital costs. The goal of this quality improvement project is to achieve 90% appropriateness of RBC transfusion in 18 hospitals across Ontario and Alberta over a period of two years. In order to achieve this, we will carry out an intervention which includes implementing RBC transfusion hospital guidelines, focused education of nurses and doctors, medical laboratory technologist screening of transfusion orders, and monthly feedback to ordering physicians regarding unnecessary transfusions.||Ongoing|
|Transfusion-Associated Circulatory Overload Best Eliminated With Lasix (TACO-BEL-1)||Dr. Jacob Pendergrast||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. Patients will be randomly allocated to receive either furosemide (20mg intravenous) or placebo (saline) within 60 minutes of starting a red blood cell (RBC) transfusion. Randomization will be stratified by centre and renal dysfunction (creatinine clearance ≥ 60 mL/min or < 60 mL/min). This is a blinded trial: patients, care-providers (physicians and nurses), data collectors, outcome adjudicators, and data analysts will not be aware of group allocation.||Completed with manuscript in progress|
|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.||Completed- published in Transfusion|
|National evaluation of platelet transport bags to reduce wastage||Dr. Jeannie Callum||Annually in Canada 874 platelets are discarded due to improper storage after issue from the blood transfusion laboratory. The estimated cost of platelet wastage is $240,089, assuming 70% buffy coat pools and 30% apheresis platelets. Platelets are in chronic short supply in Canada due to supply-demand mismatch during surges in use. Data from the multisite Pittsburgh transfusion service found that the use of platelet transport bags significantly reduced wastage. When platelets are transported to locations with refrigeration or blood coolers, it is a common error for nurses and physicians (transport medics, trauma surgeons and anaesthesiologists) to place the products in cooling devices with red cells due to inattention and lack of knowledge. The commonly cited reason is to keep all blood products together for “safety” reasons. Chilled platelets undergo modifications to their cell surface proteins which result in rapid clearance from the circulation post transfusion. The goal of this small project is to determine if the same strategy would be effective in the top 50 hospitals across Canada with the highest numerical loss of platelets. Re-usable platelet bags will be distributed to the hospitals together with a standard operating procedure and a PowerPoint with audio file for training of both the technologists and the clinical team. We hypothesize a 35% decrease in platelet wastage (cost savings $84,000).||Ongoing|