Trial NCT04345523
Publication Avendaño-Solà C, medRxiv, 2020
Dates: 2020-04-04 to 2020-07-10
Funding: Public/non profit (Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III)
| Methods | |
| RCT | |
| Location :
Multicenter / Spain Follow-up duration (days): 29 | |
| Inclusion criteria | Written informed consent prior to performing study procedures. Witnessed oral consent will be accepted in order to avoid paper handling. Written consent by patient or representatives will be obtained as soon as possible Male or female adult patient ≥18 years of age at time of enrolment Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR in naso/oropharyngeal swabs or any other relevant specimen Patients requiring hospitalization for COVID-19 without mechanical ventilation (invasive or non-invasive) or high flow oxygen devices and at least one of the following: Radiographic evidence of pulmonary infiltrates by imaging (chest x-ray, CT scan, etc.), OR Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air that requires supplemental oxygen No more than 12 days between the onset of symptoms (fever or cough) and treatment administration day |
| Exclusion criteria | Requiring mechanical ventilation (invasive or non-invasive) or high flow oxygen devices More than 12 days since symptoms (fever or cough) Participation in any other clinical trial of an experimental treatment for COVID-19 In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments Any incompatibility or allergy to the administration of human plasma Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30) |
| Interventions | |
| Treatment
Convalescent plasma (250-300ml) Co-Intervention: Standard care |
|
| Control
Standard care Definition of Standard care: All patients received standard of care (SOC), including allsupportive and specific treatments with off-label marketed medicines used according to local ornational recommendations | |
| Participants | |
| Randomized 81 participants (n1=38 / n2= 43) | |
| Characteristics of participants N=81 Mean age : 60.8 44 males Severity : Mild: n=0 / Moderate: n=81/ Severe: n=0 Critical: n=0 | |
| Primary outcome | |
| In the register Proportion of patients in categories 5, 6 or 7 of the 7-point ordinal scale at day 15 Ordinal scale: 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices 6. Hospitalized, on invasive mechanical ventilation or ECMO 7. Death | |
| In the report Proportion of patients in categories 5, 6 or 7 at day 15 of the study | |
| Documents avalaible |
Protocol NR Statistical plan NR 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 all available versions of the pre-print, the study registry was used in data extraction and risk of bias assessment. There is no change from the trial registration in the intervention and control treatments. Some pre-specified secondary outcomes and exclusion criteria were not included in the pre-print. According to information in the Supplementary Appendix, protocol changes were made (including adjustments to the eligibility criteria during recruitment) and the "final protocol is included in the supplementary material to this publication". DSMB assessments were performed and the Steering Committee decided to stop recruitment due to the drastic fall in recruitment related to pandemic control in Spain (only 6 new patients in 5 weeks) on 10 July. Quote: "The trial was halted prematurely on July 10, 2020, shortly after the first interim analysis (cut-off date June 2, 2020), primarily driven by a drastic fall in recruitment, and despite having not reach futility or efficacy stop criterion". As a result, final follow-up (day 29) for all patients were not achieved as well as the sample size specified in the registry. |