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, 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

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 O2 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 O2 therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO2/FiO2 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.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Consort flow diagram. COPLA, COVID-19 convalescent plasma; SMT, standard medical therapy.
Figure 2
Figure 2
Comparison of ordinal scale in both treatment groups. SMT, standard medical therapy.
Figure 3
Figure 3
Progression of antibody titres in both groups in patients with no baseline titres. RBD, receptor-binding domain.
Figure 4
Figure 4
Impact of titres and transfusion timings on ordinal scale.
Figure 5
Figure 5
Comparison of mortality in both treatment groups. SMT, standard medical therapy.

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