Trial NCT04479163
Publication Libster R, N Engl J Med, 2021 (published paper)
Dates: 2020-06-04 to 2020-10-25
Funding: Public/non profit (The Bill & Melinda Gates Foundation; The Fundacion INFANT Pandemic Fund)
Conflict of interest: Yes

Methods
RCT
Blinding: double blinding
Location : Multicenter / Argentina
Follow-up duration (days): 25
Inclusion criteriaAge ≥ 75 or age 65-74 with at least 1 of the following comorbidities: arterial hypertension, diabetes, obesity, chronic obstructive pulmonary disease, heart disease, chronic kidney disease
Last 48 hours: (A)Axillary temperature ≥ 37.5oC or febrile equivalent, combined with (a) dry cough and/or (b) breathing difficulty and/or (c) odinophagia and/or (d) anosmia/dysgeusia and/or (e) any of the following symptoms: fatigue, anorexia, myalgias or rhinorrhea.
Confirmed diagnosis SARS-Cov2 by RT-PCR
Give Informed consent
Exclusion criteriaSevere respiratory disease, Cardiac insufficiency, Chronic renal failure, Primary hypogammaglobulinemias, Myelodysplastic syndromes, Chronic linfoproliferative syndromes,Monoclonal gammapathies,Known hypersensitibility, Active cancer, HIV, HBV or HCV infection,Chronic administration of immunosuppressants, Body transplant history,Chronic liver disease, Chronic lung disease with oxygen requirement
Interventions
Treatment
Convalescent plasma
250 mL IV infusion once off over a period of 1.5 to 2.0 hours.
Control
Placebo
Duration : 1 day
Participants
Randomized
160 participants (n1=80 / n2= 80)
Characteristics of participants
N=160
Mean age : 77.2
60 males
Severity : Mild: n=160 / Moderate: n=0/ Severe: n=0 Critical: n=0
Primary outcome
In the register
Development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93% [ Time Frame: From 12 hours post infusion to day 15 post infusion ]
In the report
Development of severe respiratory disease defined as a respiratory rate (RR)≥ 30 and/or an O2 sat < 93% when breathing room air determined between 12 hours after infusion of the investigational product (IP) and day 15 of study participation
Documents
available

Protocol

Yes. In English

Statistical plan

Yes

Data-sharing stated

Yes
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 In addition to the study report, the pre-print article, the trial registries, study protocol, statistical analysis plan and supplementary materials were used in data extraction and assessment of the risk of bias
There were no substantive differences between the pre-print article and the trial registries, study protocol and statistical analysis plan in the study population, procedures, treatments or outcomes.
Quote: "On July 22 2020, we amended the protocol to include a fourth secondary endpoint including any of the three endpoints described above, alone or in combination."
Of note, masking was quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) in the trial registry.
The study was terminated after achieving 76% of its target sample size due to a decline in COVID-19 cases.
Quote: "Eventually, COVID-19 cases in the region decreased considerably and, by late September and early October, we were enrolling one subject per week. This enrollment pace projected at best ~5 months to complete the study in the unlikely case of the virus remaining in circulation at a constant rate. Consequently, after discussions with the DSMB and having enrolled 76% of the target population, the principal investigator (FPP) and lead sub-investigators (RL, GPM and DW) decided it would be logistically impossible, and ethically questionable given the urgency of the problem, to continue the study, and stopped to examine the results."
Four subjects in the intervention group and two subjects in the control group lost eligibility by reaching the primary endpoint before receiving the intervention product. A modified ITT analysis was also conducted.
On 10th of March, 2021, this study was updated based on the published report.
On March 29th, 2021, we received additional information from authors on this study. This study was updated with data from contact with authors on June 14th, 2021.