Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19

Abstract

BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.ResultsThe primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group.ConclusionCCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies.Trial registrationClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.

Keywords: COVID-19; Clinical Trials; Immunoglobulins.

Conflict of interest statement

Conflict of interest: Victor M. Corman is named together with Euroimmun on a patent application filed recently regarding the diagnosis of SARS-CoV-2 by antibody testing (“Methods and reagents for diagnosis of SARS-CoV-2 infection.” Patent application no. EP3809137A1).

Figures

Figure 1. Patient enrollment and treatment assignment.

ITT, intention to treat.

Figure 2. Occurrence of secondary outcomes.

Kaplan-Meier cumulative estimates of probability are shown. (A) The key secondary outcome time to clinical improvement compared in the CCP group (red line) and control group (blue line). Censored patients are indicated by “+”. P = 0.27 (log-rank test). (B) Probability of overall survival compared in the CCP group (red line) and control group (blue line). Censored patients are indicated by “+”. P = 0.21 (log-rank test). (C) Probability of discharge from hospital compared in the CCP group (red line) and control group (blue line). Censored patients are indicated by “+”. P = 0.24 (log-rank test). (D) Probability of discharge from ICU compared in the CCP group (red line) and control group (blue line). Censored patients are indicated by “+”. P = 0.39 (log-rank test).

Figure 3. Clinical outcomes according to ordinal severity scale.

The distribution of the clinical status according to the ordinal severity scale at baseline, day 7, day 14, day 21, and day 35 is shown for the CCP group and control group according to initial randomization, i.e., the 7 patients with crossover to receive CCP on days 15, 17, and 19 remain in the control group. *Hospitalized.

Figure 4. Occurrence of secondary outcomes by cumulative amount of transfused neutralizing units.

Kaplan-Meier cumulative estimates of probability are shown. (A) The key secondary outcome time to clinical improvement compared in the CCP subgroup that received a low cumulative amount of neutralizing units (red line), the CCP subgroup that received a high cumulative amount of neutralizing units (blue line), and the control group (green line). Censored patients are indicated by “+”. P = 0.0496 (log-rank test, high amount vs. control group). (B) Probability of overall survival compared in the CCP subgroup that received a low cumulative amount of neutralizing units (red line), the CCP subgroup that received a high cumulative amount of neutralizing units (blue line), and the control group (green line). Censored patients are indicated by “+”. P = 0.02 (log-rank test, high amount vs. control group). (C) Probability of discharge from hospital compared in the CCP subgroup that received a low cumulative amount of neutralizing units (red line), the CCP subgroup that received a high cumulative amount of neutralizing units (blue line), and the control group (green line). Censored patients are indicated by “+”. P = 0.03 (log-rank test, high amount vs. control group). (D) Probability of discharge from ICU compared in the CCP subgroup that received a low cumulative amount of neutralizing units (red line), the CCP subgroup that received a high cumulative amount of neutralizing units (blue line), and the control group (green line). Censored patients are indicated by “+”. P = 0.04 (log-rank test, high amount vs. control group).