Bleeding, Cardiac Surgery, Cardiopulmonary Bypass, Platelets
Conditions
Keywords
Blood Platelets, Cardiac surgical procedure, Blood Preservation/Methods, Blood Preservation/Adverse Effects
Brief summary
PLTS-1 is a multicentre, randomized, controlled, pilot trial, using a conventional, parallel group, two-armed design at 2 cardiac surgery centres in Canada. The study is designed to assess the feasibility of a future, definitive RCT to determine the non-inferiority of cold-stored platelets compared to conventional platelets with respect to hemostatic effectiveness (total number of allogeneic blood products transfused within 24 hours after CPB), as well as safety.
Interventions
BIOLOGICALDelayed Cold-Stored Buffy Coat Platelets
To prepare cold-stored platelets, blood banks will transition conventional room temperature platelets up to 4 days after collection (with agitation) to cold-storage (at 1-6 C without agitation) for a minimum of 1 day (24 hours) and a maximum of 10 days after collection (for a total shelf life of ≤ 14 days after collection). Thus, cold-stored platelets will be produced and stored the same way as room temperature platelets up until their transition to cold-storage, ensuring similar products differing only in storage conditions and expiration date (as cold-stored platelets will have an expiration date beyond the current 5 days for pathogen inactivated platelets or 7 days for bacterially cultured platelets). Pathogen reduced platelets will be used for the pilot study (Canada is transitioning in 2022-23 to pathogen-reduced platelets and one site has already transitioned).
BIOLOGICALRoom Temperature Buffy Coat Platelets
Room temperature stored platelets are prepared from donor whole blood, which is centrifuged to collect the buffy coat layer containing platelets. Seven ABO matched buffy coats from male and/or female donors are pooled in 280 ml of platelet additive solution and split into a single dose after pathogen inactivation, resulting in a product with a final platelet count of approximately 1300 x 109. Pathogen inactivated platelets (shelf-life of 5 days, with recent Health Canada approval for an extension of the shelf-life to 7 days), will be used as Canada is transitioning in 2022-23 to pathogen-inactivated platelets and one site has already transitioned.
Sponsors
University Health Network, Toronto
Kingston Health Sciences Centre
Canadian Blood Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This will be a blinded randomized trial, with clinical personnel, patients, family members, and outcome assessors blinded to group allocation. Given that the platelets will be different temperatures (but identical in appearance), an unblinded blood bank technologist, who will not have access to the collected study data, will blind the platelets by placing them in an insulated tamper-proof container accompanied by a pair of disposable insulated gloves. The clinician(s) directly handling the product at the time of transfusion will wear the insulated gloves to prevent unblinding (simulations have shown this to be an effective strategy). The platelets will also have blinded study labels and come prepared in identical collection bags.
Intervention model description
PLTS-1 is a multicentre, randomized, controlled, pilot trial, using a conventional, parallel group, two-armed design at 2 cardiac surgery centres in Canada.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adult (≥18 years old) patients undergoing elective cardiac surgery with CPB will be eligible for inclusion if they are planned to undergo at least moderately complex surgery or have a preoperative platelet count ≤150,000 x106/L (this is a group at high risk of requiring platelet transfusions post-CPB). Moderately complex index surgery is defined as: 1. repair/replacement of more than one valve; 2. aorta (root/ascending/arch) replacement; 3. any combination of coronary artery bypass grafting, valve repair/replacement, or aorta (root/ascending/arch) replacement; or 4. re-do procedures consisting of a repair or revision of a prior cardiac intervention.
Exclusion criteria
Patients will be excluded if cold-stored platelets are not going to be available at the time of surgery or if the patient: 1. has a congenital or acquired hemostatic disorder (including platelet refractoriness due to anti-platelet and anti-human leukocyte antigen \[HLA\] antibodies) and/or requires specially matched platelets (including patients with anaphylaxis to blood due to Immunoglobulin A \[IgA\] deficiency), 2. has known contraindications to heparin, thereby excluding cases where non-reversible anticoagulants (i.e. argatroban) are used, 3. is on warfarin or direct oral anticoagulants (dabigatran, rivaroxaban, apixaban or edoxaban) within 3 days prior to surgery, 4. is on antiplatelet drugs within 5 days prior to surgery (excluding acetylsalicylic acid \[ASA\]), 5. refuses allogeneic blood products, 6. has a known pregnancy, 7. has already enrolled in this study, 8. is enrolled in another interventional clinical trial where routine care and management are altered, 9. has hemodynamic instability defined as critical care admission, vasopressor, or inotrope dependence prior to index surgery, or 10. has pre-operative requirement for, or expected post-operative dependence upon mechanical circulatory support (i.e., intra-aortic balloon pump, ventricular assist device).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility Outcome 1: Adequate Patient Recruitment | through study completion, an average of 1 year. | Adequate recruitment (defined as ≥ 15% of eligible patients enrolled per centre per month to target consistent levels of enrollment). |
| Feasibility Outcome 2: Adequate cold-stored platelet supply | through study completion, an average of 1 year. | Adequate cold-stored platelet supply (defined as appropriate product available at the time of surgery for ≥90% of patients randomized to the cold-stored platelet group). |
| Feasibility Outcome 3: Adequate clinician adherence to randomization assignment. | through study completion, an average of 1 year. | Adequate clinician adherence to randomization assignment (defined as \>90% of all randomized patients are administered the assigned product). |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORJustyna Bartoszko, MD
University Health Network, Toronto
PRINCIPAL_INVESTIGATORJeannie Callum, MD
Kingston Health Sciences Centre
Outcome results
None listed