Therapeutic Use of Convalescent Plasma in the Treatment of Patients With Moderate to Severe COVID-19

May 5, 2026 updated by: Riana Cockeran, South African National Blood Service

A Prospective, Randomized, Placebo-controlled, Double-blinded, Phase III Clinical Trial of the Therapeutic Use of Convalescent Plasma in the Treatment of Patients With Moderate to Severe COVID-19

A prospective, randomized, placebo-controlled, double-blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Full Title: A prospective, randomized, placebo-controlled, double-blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19.

Short Title: PROTECT-Patient study

Aim: Assess the safety and efficacy of COVID-19 convalescent plasma (CCP) as a therapeutic treatment for hospitalised patients with moderate to severe COVID-19

Study Design: Randomised, double-blinded, placebo-controlled, phase III clinical trial

Intervention: Randomised 1:1 to either CCP plus standard of care (SOC) or to SOC plus placebo (200 mL normal saline)

Active Agent: A single unit of approximately 200-250 mL of CCP that contains anti-SARS-CoV-2 collected by plasmapheresis from a volunteer who recovered from COVID19 with SOC as determined by local practice and guidelines.

Placebo: A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines

Sample Size: 600

Study Population: Consenting adult inpatients with moderate to severe COVID-19, not requiring invasive ventilation, who are admitted to a participating public or private sector hospital and who are not enrolled in another COVID-19 treatment trial.

Settings: Participating public and private sector hospitals in South Africa

Study Type

Interventional

Enrollment (Actual)

102

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Free State
      • Bloemfontein, Free State, South Africa, 9301
        • Universitas Hospital
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7786
        • Mitchells Plain Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Laboratory confirmed SARS-CoV-2 by positive RT-PCR on any respiratory sample;
  • Age ≥ 18 years;
  • Require hospital admission for COVID-19 pneumonia as defined by the presence of pulmonary infiltrates on chest x-ray;
  • Moderate to severe Covid-19 disease, defined as: SpO2 ≤ 93% on room air; plus requiring non-invasive oxygen therapy (WHO R&D BOSCI 4 or 5
  • Signed informed consent;
  • Pregnant women will be allowed to participate.

Exclusion Criteria:

  • Current participation in another therapeutic clinical trial for COVID-19;
  • Invasive mechanical ventilation;
  • Expected survival < 24 hours based on clinical assessment (however, the study does not exclude critically ill patients who are not, due to resource limitations, candidates for critical care admission and/or mechanical ventilation);
  • Known hypersensitivity to immunoglobulin or any components of the formulation;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
A single unit of approximately 200-250 mL of CCP that contains anti-SARS-CoV-2 collected by plasmapheresis from a volunteer who recovered from COVID19 with SOC as determined by local practice and guidelines.
Biological: COVID-19 convalescent plasma (CCP) plus standard of care (SOC)
A single unit of approximately 200-250 mL of CCP that contains anti-SARS-CoV-2 collected by plasmapheresis from a volunteer who recovered from COVID19 with SOC as determined by local practice and guidelines.
Placebo Comparator: Arm 2
A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines.
Biological: Standard of care (SOC) plus placebo
A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Improvement
Time Frame: Day 28
Proportion of participants with successful treatment outcome, defined as clinical improvement (≥ 2 points on WHO R&D BOSCI 1) by Day 28 post-randomisation.
Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events of special interest
Time Frame: Day 28
1. Proportion of participants with adverse events of special interest (Transfusion-Associated Circulatory Overload (TACO); Transfusion-Related Acute Lung Injury (TRALI); allergic transfusion reaction).
Day 28
Serious Adverse Events
Time Frame: Day 28
2. Proportion of participants with serious adverse events.
Day 28
Survival
Time Frame: Day 28
3. Proportion of participants surviving at Day 28 post-randomisation.
Day 28
Invasive mechanical ventilation
Time Frame: Day 28
4. Proportion of participants requiring invasive mechanical ventilation.
Day 28
Disease severity
Time Frame: Day 28
5. Proportion of participants with moderate and severe ARDS.
Day 28
Time to outcomes of interest
Time Frame: Day28
6. Time from randomization to death, clinical improvement, ICU admission, and invasive mechanical ventilation.
Day28
Length of stay meausures
Time Frame: Day28
7. Duration of hospitalisation, ICU stay, and mechanical ventilation in survivors.
Day28
SARS-CoV PCR
Time Frame: Day28
8. Proportion negative SARS-CoV-2 PCR at Day 28; time to viral clearance (PCR-negativity); change in SARS-CoV-2 PCR Ct value.
Day28
Inflammatory markers
Time Frame: Day28
9. Proportion with and time to normalisation of inflammatory markers, including CRP, lymphocyte count, D-dimer, ferritin.
Day28
Radiography
Time Frame: Day28
10. Worsening of radiographic abnormalities.
Day28
Fever & Hypoxia
Time Frame: Day28
11. Proportion with and time to resolution of fever and hypoxia.
Day28
patients with HIV infection and other comorbidities
Time Frame: Day 28
12. Proportion of patients with HIV infection and other comorbidities (obesity, diabetes, hypertension) with primary efficacy outcome.
Day 28
Timing of IP & Efficacy Outcome
Time Frame: Day 28
13. Relationship between timing of transfusion from symptom onset and primary efficacy outcome.
Day 28
Neutralising Ab
Time Frame: Day28
14. Relationship between convalescent plasma neutralizing antibody titers and primary efficacy outcome
Day28
SARS CoV Antibody titre
Time Frame: Day28
15. Comparison of anti-SARS-CoV-2 titer dynamics between treatment arms
Day28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

South African National Blood Service

Investigators

  • Study Chair: Sean Wasserman, A/Professor, CIDRI-Africa, University of Cape Town
  • Principal Investigator: Karin vandenBerg, Dr, South African National Blood Service

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2020

Primary Completion (Actual)

December 30, 2021

Study Completion (Actual)

July 31, 2022

Study Registration Dates

First Submitted

August 12, 2020

First Submitted That Met QC Criteria

August 17, 2020

First Posted (Actual)

August 18, 2020

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 5, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PROTECT-Patient trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Where available and applicable, the results of this study will be reported to the appropriate scientific and management divisions of participating institutions. In addition, interim results may be communicated to lay press if doing so is deemed appropriate and relevant by the Study Management Committee. Interim and final results will be presented at various scientific congresses, meeting and in appropriate peer-reviewed scientific journals. Under no circumstances will personal identifier be revealed to any party not legally entitled to such information.

IPD Sharing Time Frame

Undecided

IPD Sharing Access Criteria

undecided

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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