Trial NCT04348656
Publication Begin P, medRxiv, 2021 (preprint)
Dates: 2020-05-14 to 2021-01-29
Funding: Public/non profit (Canadian Institutes of Health Research; Ontario COVID-19 Rapid Research Fund; Toronto COVID-19 Action Initiative 2020 (University of Toronto); University Health Network Emergent Access Innovation Fund; University Health Academic Health Science Centre Alternative Funding Plan (Sunnybrook Health Sciences Centre); Ministère de l'Économie et de l'Innovation (Québec); Fond de Recherche du Québec en Santé; Saskatchewan Ministry of Health; University of Alberta Hospital Foundation; Alberta Health Services COVID-19 Foundation Competition;
Sunnybrook Health Sciences Centre Foundation; Fondations CHU Ste-Justine; The Ottawa Hospital Academic Medical Organization; The Ottawa Hospital Foundation COVID-19 Research Fund; Fondation du CHUM; Sinai Health System Foundation and McMaster University. These did not have any role in the writing of the manuscript or the decision to submit it for publication. The authors did not receive payments from any pharmaceutical company or other agency to write this article.)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Canada, USA, Brazil Follow-up duration (days): 30 | |
| Inclusion criteria | >16 in Canada or >18 years of age in the United States and Brazil; admitted to the hospital ward with confirmed COVID-19; required supplemental oxygen; availability of ABO-compatible convalescent plasma from donors who had recovered from COVID-19 infection was an eligibility requirement. |
| Exclusion criteria | more than 12 days from the onset of respiratory symptoms; imminent or current intubation; a contraindication to plasma transfusion; or a plan for no active treatment. |
| Interventions | |
| Treatment
Convalescent plasma 500 mL IV infusion once-off (or 2 units of 250 mL from 1 or 2 donors) |
|
| Control
Standard care ( / ) Definition of Standard care: usual medical care as per routine practices at each site | |
| Participants | |
| Randomized 940 participants (n1=627 / n2= 313) | |
| Characteristics of participants N=940 Mean age : 67.5 554 males Severity : Mild: n=0 / Moderate: n=*/ Severe: n=* Critical: n=0 | |
| Primary outcome | |
| In the register Intubation or death [Time Frame: Day 30] | |
| In the report composite of intubation or death by day 30 | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated
|
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | This trial was terminated early due to futility upon interim analysis. In addition to the preprint, the protocol, statistical analysis plan and study registry were used in data extraction and risk of bias assessment. The study randomized 940 out of the pre-planned sample size of 1200. There are no substantive changes from the registry/protocol in the study population, procedures, intervention and control treatments. The primary outcome indicated in the registry/protocol reflects the primary outcome reported in the paper. Unblinded study. No information on administration in each group of biologics co-interventions of interest. The study reports 4 vs 4 participants of the intention-to-treat population not to be on oxygen at randomization. While mortality (D28) results were based on all cause mortality, mortality (D60 and more) and time to death as well as time to WHO score 7 and above was solely considering in-hospital mortality. |