Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial)
Meenu Bajpai, Ashish Maheshwari, Vikas Dogra, Suresh Kumar, Ekta Gupta, Pratibha Kale, Vandana Saluja, Sherin S Thomas, Nirupama Trehanpati, Chhagan Bihari, Reshu Agarwal, Praveen Bharti, Prabha Shankar, Javid Hussain, Karan Chhabra, Amita Gupta, Ashad Narayanan, Sarika Agarwal, Shruti Jain, Ankit Bhardwaj, Guresh Kumar, Birendra Kumar Yadav, Shiv Kumar Sarin
BMJ Open, doi:10.1136/bmjopen-2021-055189
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, openlabelled, 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.
Competing interests None declared. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not applicable. Ethics approval This study involves human participants and was approved by Institute of Liver and Biliary Sciences, New Delhi, Reference number or ID for ethics: IEC/2020/77/MA05. Participants gave informed consent to participate in the study before taking part. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available on reasonable request. Data (unpublished data in its row form in Microsoft excel sheet) will be available with principal investigator of the study and it will be available for researcher in unidentified data form on reasonable request to principal investigator till 5 years from date of publication. Rest all data relevant to the study are included in the article or uploaded as online supplemental information Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and..
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'abstract': '<jats:sec><jats:title>Importance</jats:title><jats:p>No proven treatment is available for '
'severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under '
'investigation.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To '
'compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 '
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'participants</jats:title><jats:p>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 '
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'group.</jats:p></jats:sec><jats:sec><jats:title>Intervention</jats:title><jats:p>One group '
'received COPLA with SMT (n=200), and another group received SMT only '
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'measures</jats:title><jats:p>Primary outcome was time to clinical improvement measured by a '
'two-point reduction in the ordinal scale. Secondary outcomes included duration of '
'O<jats:sub>2</jats:sub>therapy, the proportion of patients on mechanical ventilation at '
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'to a two-point reduction in the ordinal scale in both groups was 9\u2009days (IQR=7–13) '
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