COVID-19, SARS-CoV-2 Infection, Severe Acute Respiratory Syndrome Coronavirus 2
Conditions
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
Interventions
BIOLOGICALCOVID-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.
BIOLOGICALStandard of care (SOC) plus placebo
A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines
Sponsors
South African National Blood Service
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
South Africa
Contacts
STUDY_CHAIRSean Wasserman, A/Professor
CIDRI-Africa, University of Cape Town
PRINCIPAL_INVESTIGATORKarin vandenBerg, Dr
South African National Blood Service
Outcome results
None listed