1.
A Scoping Review of Registered Clinical Trials of Convalescent Plasma for COVID-19 and a Framework for Accelerated Synthesis of Trial Evidence (FAST Evidence)
Zheng K, Liao G, Lalu MM, Tinmouth A, Fergusson DA, Allan DS
Transfusion Medicine Reviews. 2020
Abstract
Many parallel studies of convalescent plasma with modest enrolment projections have been launched for the treatment of COVID-19. By pooling data from multiple parallel studies that are similar, we can increase the effective sample size and achieve enough statistical power to determine effectiveness more quickly through meta-analysis. A scoping review of registered clinical trials of convalescent plasma for COVID-19 was conducted to assess the feasibility of performing a rapid and timely meta-analysis that will support accelerated review for approval and implementation. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched April 23, 2020. Trials were included if they utilized convalescent plasma to treat or prevent COVID-19. Forty-eight registered trials (projected to enroll more than 5000 subjects) of convalescent plasma were identified and included for analysis. The majority of studies (33 studies with 4440 projected enrolment) will address the treatment of severe and/or critical cases of COVID-19. Twenty-nine studies are controlled and 17 of these are reported as actively recruiting. The combined enrolment of patients from similar studies should be sufficient to determine meaningful improvements in mortality, rates of admission to intensive care and need for mechanical ventilation by the end of 2020-sooner than any individual study could determine effectiveness. Accessing supplemental outcome data from investigators may be needed; however, to align reporting of some outcomes from these studies. Heterogeneity in product potency due to different antibody titers is anticipated and studies using conventional treatment as controls instead of placebo may complicate our understanding of efficacy. Convalescent plasma is being tested in ongoing controlled studies, largely to treat severe and/or critical cases of COVID-19. Sufficient combined power to detect clinically important reductions in multiple outcomes, including mortality, is expected by September 2020. Regulatory approval, funding and implementation by blood operators could be accelerated by planned meta-analysis as study results become available.
2.
Liberal Versus Restrictive Red Blood Cell Transfusion Thresholds in Hematopoietic Cell Transplantation: A Randomized, Open Label, Phase III, Noninferiority Trial
Tay J, Allan DS, Chatelain E, Coyle D, Elemary M, Fulford A, Petrcich W, Ramsay T, Walker I, Xenocostas A, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;:Jco1901836
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Editor's Choice
Abstract
PURPOSE Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood. PATIENTS AND METHODS We performed a noninferiority randomized controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin [Hb] threshold < 70 g/L) or liberal (Hb threshold < 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy. RESULTS A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group (P < .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units [standard deviation, 4.81 units] v 5.02 units [standard deviation, 6.13 units]; P = .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, -2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies. CONCLUSION In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.
PICO Summary
Population
Patients with haematologic malignancies requiring haematopoietic cell transplantation (HCT) across four Canadian HCT centres, (n=300).
Intervention
Restrictive red blood cell transfusion (RBC) strategy (haemoglobin [Hb] threshold < 70 g/L), (n= 150).
Comparison
Liberal RBC transfusion strategy (Hb threshold < 90 g/L), (n= 150).
Outcome
After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group. The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units vs. 5.02 units). After adjusting for transfusion type and baseline Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points), which was non-inferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies.
3.
Optimal transfusion practices after allogeneic hematopoietic cell transplantation: a systematic scoping review of evidence from randomized controlled trials
Christou G, Iyengar A, Shorr R, Tinmouth A, Saidenberg E, Maze D, Tay J, Bredeson C, Allan DS
Transfusion. 2016;56((10):):2607-2614
Abstract
BACKGROUND Integrating evidence from randomized controlled trials (RCTs) into patient care is needed to optimize patient outcomes. Transfusion support during allogeneic hematopoietic cell transplantation (alloHCT) is a cornerstone of essential supportive care, yet optimal transfusion practices remain unclear. STUDY DESIGN AND METHODS A scoping review of RCTs in alloHCT was conducted and 14 full-length articles on transfusion practice were identified that reported clinical outcomes after alloHCT. RESULTS Eight RCTs compared various interventions related to platelet (PLT) transfusion, addressing product storage duration, dosage, and threshold for transfusion. Restrictive prophylactic PLT transfusion strategies were successful at reducing PLT consumption without impacting clinical outcomes. One study, however, reported increased bleeding associated with a strategy whereby patients did not receive prophylactic PLT transfusions. One study of thrombopoietin was associated with reduced PLT transfusion events but no difference in clinical outcomes compared to placebo. Six RCTs examined the utility of recombinant erythropoietin (EPO) in reducing red blood cell (RBC) transfusion dependence. Four trials reported an increase in hemoglobin levels while five studies demonstrated a reduction in RBC utilization; however, clinical outcomes were variably reported and no differences were identified. There were no RCTs examining RBC transfusion strategies, plasma transfusion, or plasma-derived protein administration. CONCLUSION Prophylactic PLT transfusion when PLTs are fewer than 10 x 109 /L can prevent bleeding and is consistent with recent guidelines. Thrombopoietin and EPO can reduce transfusion requirements; however, potential safety concerns remain and the lack of improvement in clinical outcomes and high cost may limit use. Additional RCTs are needed, particularly with regard to RBC transfusion thresholds, to refine best practices after alloHCT.