Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial

Abstract

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia.

Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia.

Design, setting, and participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible.

Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations.

Main outcomes and measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization.

Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04).

Conclusions and relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days.

Trial registration: ClinicalTrials.gov Identifier: NCT04716556.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Puoti reported receiving personal fees and nonfinancial support from Abbvie, grants and nonfinancial support from Gilead Science, and personal fees from Merck and Theratechnologies outside the submitted work. Dr Bonfanti reported receiving personal fees from Viiv, Gilead, Jannsen Pharmaceuticals, Merck, and Pfizer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Flowchart

Abbreviations: ITT, intention to treat population; mITT, modified intention to treat population; PP, per protocol population. aData not available for 3 patients (1 in convalescent plasma plus standard therapy group; 2 in standard therapy group).

Figure 2.. Primary End Point in the Modified Intention-to-Treat Population, Subgroup Analysis

The primary end point was worsening respiratory failure or death within 30 days from randomization. Only 1 patient in the convalescent plasma (CP) plus standard therapy (ST) group and 7 in the ST group did not receive corticosteroids. LMWH indicates low–molecular weight heparin; NAb, neutralizing antibody.

Figure 3.. Primary End Point Distribution According to the Study Groups and Baseline Partial Pressure Of Oxygen–to–Fraction of Inspired Oxygen (Pao2/Fio2) Ratio Categories in the Modified Intention to Treat Population

The primary end point was worsening respiratory failure or death within 30 days from randomization. Test for interaction: Pao2/Fio2 250 to 299 mm Hg vs 200 to 249 mm Hg, P > .99; Pao2/Fio2 300 mm Hg or greater vs 200 to 249 mm Hg, P = .06.