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

Phase 3

• Conditions: SARS-CoV-2 Infection; COVID-19; Severe Acute Respiratory Syndrome Coronavirus 2
• Interventions: Biological: COVID-19 convalescent plasma (CCP) plus standard of care (SOC); Biological: Standard of care (SOC) plus placebo

• Registration Number: NCT04516811
• Lead Sponsor: South African National Blood Service

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

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 Timeline

• Study First Submitted: 2020-08-12
• Study First Submitted QC: 2020-08-17
• Study First Posted: 2020-08-18
• Status Verified: 2020-09
• Study Start: 2020-09-21
• Last Update Submitted: 2020-09-24
• Last Update Posted: 2020-09-25
• Primary Completion: 2021-12-30
• Study Completion: 2022-07-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 600

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	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.
Arm 2	Standard of care (SOC) plus placebo	A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Fever & Hypoxia	Day28	11. Proportion with and time to resolution of fever and hypoxia.
Serious Adverse Events	Day 28	2. Proportion of participants with serious adverse events.
Invasive mechanical ventilation	Day 28	4. Proportion of participants requiring invasive mechanical ventilation.
Time to outcomes of interest	Day28	6. Time from randomization to death, clinical improvement, ICU admission, and invasive mechanical ventilation.
Timing of IP & Efficacy Outcome	Day 28	13. Relationship between timing of transfusion from symptom onset and primary efficacy outcome.
Length of stay meausures	Day28	7. Duration of hospitalisation, ICU stay, and mechanical ventilation in survivors.
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.
SARS CoV Antibody titre	Day28	15. Comparison of anti-SARS-CoV-2 titer dynamics between treatment arms
Neutralising Ab	Day28	14. Relationship between convalescent plasma neutralizing antibody titers and primary efficacy outcome
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).
Disease severity	Day 28	5. Proportion of participants with moderate and severe ARDS.
Survival	Day 28	3. Proportion of participants surviving at Day 28 post-randomisation.
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.
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.

Trial Locations

Locations (2)

Mitchells Plain Hospital; 🇿🇦 Cape Town, Western Cape, South Africa

Universitas Hospital; 🇿🇦 Bloemfontein, Free State, South Africa