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

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ClinicalTrials.gov Identifier: NCT04516811
Recruitment Status : Recruiting
First Posted : August 18, 2020
Last Update Posted : September 25, 2020
Sponsor:
Information provided by (Responsible Party):
Karin van den Berg, South African National Blood Service

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
Estimated 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.
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 : September 21, 2020
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : July 31, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. Serious Adverse Events [ Time Frame: Day 28 ]
    2. Proportion of participants with serious adverse events.

  3. Survival [ Time Frame: Day 28 ]
    3. Proportion of participants surviving at Day 28 post-randomisation.

  4. Invasive mechanical ventilation [ Time Frame: Day 28 ]
    4. Proportion of participants requiring invasive mechanical ventilation.

  5. Disease severity [ Time Frame: Day 28 ]
    5. Proportion of participants with moderate and severe ARDS.

  6. Time to outcomes of interest [ Time Frame: Day28 ]
    6. Time from randomization to death, clinical improvement, ICU admission, and invasive mechanical ventilation.

  7. Length of stay meausures [ Time Frame: Day28 ]
    7. Duration of hospitalisation, ICU stay, and mechanical ventilation in survivors.

  8. 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.

  9. Inflammatory markers [ Time Frame: Day28 ]
    9. Proportion with and time to normalisation of inflammatory markers, including CRP, lymphocyte count, D-dimer, ferritin.

  10. Radiography [ Time Frame: Day28 ]
    10. Worsening of radiographic abnormalities.

  11. Fever & Hypoxia [ Time Frame: Day28 ]
    11. Proportion with and time to resolution of fever and hypoxia.

  12. 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.

  13. Timing of IP & Efficacy Outcome [ Time Frame: Day 28 ]
    13. Relationship between timing of transfusion from symptom onset and primary efficacy outcome.

  14. Neutralising Ab [ Time Frame: Day28 ]
    14. Relationship between convalescent plasma neutralizing antibody titers and primary efficacy outcome

  15. SARS CoV Antibody titre [ Time Frame: Day28 ]
    15. Comparison of anti-SARS-CoV-2 titer dynamics between treatment arms


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04516811


Contacts
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Contact: Cynthia Nyoni +27117619279 ext 9279 Cynthia.Nyoni@sanbs.org.za
Contact: Mpumi Maxebengula, BCom +27214066497 ext 6497 mpumi.maxebengula@uct.ac.za

Locations
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South Africa
Universitas Hospital Not yet recruiting
Bloemfontein, Free State, South Africa, 9301
Contact: Jacques Malherbe         
Mitchells Plain Hospital Recruiting
Cape Town, Western Cape, South Africa, 7786
Contact: Sean Wasserman         
Sponsors and Collaborators
South African National Blood Service
Investigators
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Study Chair: Sean Wasserman, A/Professor CIDRI-Africa, University of Cape Town
Principal Investigator: Karin vandenBerg, Dr South African National Blood Service
More Information
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Publications of Results:

Other Publications:

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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: August 18, 2020    Key Record Dates
Last Update Posted: September 25, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Undecided
Access Criteria: undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Severe Acute Respiratory Syndrome
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases