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

Sponsor

South African National Blood Service (Other)

Overall Status

Recruiting

CT.gov ID

NCT04516811

Collaborator

(none)

600

Enrollment

Locations

Arms

22.3

Anticipated Duration (Months)

300

Patients Per Site

13.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
COVID-19 SARS-CoV-2 Infection Severe Acute Respiratory Syndrome Coronavirus 2	Biological: COVID-19 convalescent plasma (CCP) plus standard of care (SOC) Biological: Standard of care (SOC) plus placebo	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participant identification numbers (PIN), assigned at the screening/enrolment visit, will be used throughout the study. After signing the informed consent document, eligible participants will be randomised to one of the treatment arms, stratified by study site, age group (<=65; >65 years old) and body mass index (BMI) (<30; >=30 kg/m2). An electronic randomisation application will generate the treatment allocation. The trial Program Manager (PM), who will have no direct contact with trial participants or involvement in eligibility assessment or outcome assignment, will maintain the randomisation code.Participant identification numbers (PIN), assigned at the screening/enrolment visit, will be used throughout the study. After signing the informed consent document, eligible participants will be randomised to one of the treatment arms, stratified by study site, age group (<=65; >65 years old) and body mass index (BMI) (<30; >=30 kg/m2). An electronic randomisation application will generate the treatment allocation. The trial Program Manager (PM), who will have no direct contact with trial participants or involvement in eligibility assessment or outcome assignment, will maintain the randomisation code.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Neither participants nor the investigators will be aware of the participant's treatment allocation until the end of the study (double blinding). Blinding will be maintained by local blood bank preparing the appropriate IP and Placebo. Unmasking procedures are detailed by SOP

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Sep 21, 2020

Anticipated Primary Completion Date :

Dec 30, 2021

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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

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)

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

Outcome Measures

Primary Outcome Measures

Clinical Improvement [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Universitas Hospital	Bloemfontein	Free State	South Africa	9301
2	Mitchells Plain Hospital	Cape Town	Western Cape	South Africa	7786

Sponsors and Collaborators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Karin van den Berg, Site Principal Investigator, South African National Blood Service

ClinicalTrials.gov Identifier:

NCT04516811

Other Study ID Numbers:

PROTECT-Patient trial

First Posted:

Aug 18, 2020

Last Update Posted:

Sep 25, 2020

Last Verified:

Sep 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

COVID-19

Severe Acute Respiratory Syndrome

Study Results

No Results Posted as of Sep 25, 2020