Trial NCT04345523
Publication Avendano-Sola C, J Clin Invest, 2021 (published paper)
Dates: 2020-04-04 to 2021-02-05
Funding: Public/non profit (Government of Spain, Instituto de Salud Carlos III)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Spain Follow-up duration (days): 28 | |
| Inclusion criteria | Written informed consent prior to performing study procedures. Witnessed 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 test in naso/oropharyngeal swabs or any other relevant specimen obtained in the ongoing COVID-19 symptomatic period. Alternative tests (i.e. rapid antigenic tests) are also acceptable as laboratory confirmation if their adequate specificity has been accepted by the sponsor. 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 7 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 at screening
More than 7 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 250-300 mL IV once-off immediately after randomization. |
|
| Control
Standard care Definition of Standard care: All patients received standard of care (SOC), including all supportive and specific treatments with off-label marketed medicines used according to local or national recommendations | |
| Participants | |
| Randomized 350 participants (n1=179 / n2= 171) | |
| Characteristics of participants N=350 Mean age : 63 229 males Severity : Mild: n=74 / Moderate: n=276/ 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 | |
| In the report Proportion of patients in categories 5, 6 or 7 (noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death) at 14 days (day 15 of the study) | |
| 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 all available versions of the published journal and pre-print articles, the study registry, protocol and statistical analysis plan were 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. 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 temporarily stopped on July 10, 2020, after the first interim analysis, due to a drastic fall in recruitment (end of first wave in Spain), although prespecified futility or efficacy stop criteria had not been reached. Preliminary results of this first set of patients were publicly reported. Nevertheless, the trial recruitment was resumed shortly after, with the surge of the second wave, and the trial was finally completed as planned. On December 3, 2020, the DSMB recommended increasing the sample size by at least a 20% and the new sample size was set at 350 patients." As a result the trial achieved its target sample size. registry. This study was updated on October 8th, 2020. This study was again updated on October 4th, 2021 with data from the peer-reviewed publication. |