Abstract
Importance: No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation.
Objective: To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients.
Design, setting and participants: A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group.
Intervention: One group received COPLA with SMT (n=200), and another group received SMT only (n=200).
Main outcome measures: Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O 2 therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events.
Results: The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O 2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO 2 /FiO 2 ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group.
Conclusion and relevance: Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes.
Trial registration number: NCT04425915 .
Keywords: COVID-19; blood bank & transfusion medicine.
【저자키워드】 COVID-19, blood bank &, transfusion medicine., 【초록키워드】 Treatment, convalescent plasma, Efficacy, randomised controlled trial, therapy, Mortality, Trial, D-dimer, outcome, clinical outcomes, adverse events, SARS-CoV-2 antibody, Patient, Clinical improvement, plasma, Hospital admission, incidence, hospitalisation, Blood, TNF-α, Antibody titre, COVID-19 patient, allergic reaction, study population, median time, no difference, severe COVID-19 patients, treatment group, participant, secondary, initial, collected, proportion, conducted, median, reduction in, 1:1, 48 hour, cytokine level, in both group, IQR, on mechanical ventilation, PaO, transfused, 【제목키워드】 Trial, randomised, Convalescent plasma therapy, the patient,