Clinical trial NCT04516811: Therapeutic Use of Convalescent Plasma in the Treatment of Patients With Moderate to Severe COVID-19
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19
SARS-CoV-2 Infection
Severe Acute Respiratory Syndrome Coronavirus 2
Lead sponsor: South African National Blood Service
Sponsor class: OTHER
First posted: 2020-08-18
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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

Eligibility 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;

Primary outcomes:
measure: Clinical Improvement
timeFrame: Day 28
Secondary outcomes:
measure: Adverse Events of special interest
timeFrame: Day 28
measure: Serious Adverse Events
timeFrame: Day 28
measure: Survival
timeFrame: Day 28
measure: Invasive mechanical ventilation
timeFrame: Day 28
measure: Disease severity
timeFrame: Day 28
measure: Time to outcomes of interest
timeFrame: Day28
measure: Length of stay meausures
timeFrame: Day28
measure: SARS-CoV PCR
timeFrame: Day28
measure: Inflammatory markers
timeFrame: Day28
measure: Radiography
timeFrame: Day28
measure: Fever & Hypoxia
timeFrame: Day28
measure: patients with HIV infection and other comorbidities
timeFrame: Day 28
measure: Timing of IP & Efficacy Outcome
timeFrame: Day 28
measure: Neutralising Ab
timeFrame: Day28
measure: SARS CoV Antibody titre
timeFrame: Day28
Other outcomes:
Locations:
city: Bloemfontein
country: South Africa
facility: Universitas Hospital
state: Free State
city: Cape Town
country: South Africa
facility: Mitchells Plain Hospital
state: Western Cape
Study officials:
affiliation: CIDRI-Africa, University of Cape Town
name: Sean Wasserman, A/Professor
role: STUDY_CHAIR
affiliation: South African National Blood Service
name: Karin vandenBerg, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020 Apr;5(4):536-544. doi: 10.1038/s41564-020-0695-z. Epub 2020 Mar 2.
citation: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
citation: Zu ZY, Jiang MD, Xu PP, Chen W, Ni QQ, Lu GM, Zhang LJ. Coronavirus Disease 2019 (COVID-19): A Perspective from China. Radiology. 2020 Aug;296(2):E15-E25. doi: 10.1148/radiol.2020200490. Epub 2020 Feb 21.
citation: Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020 May;92(5):479-490. doi: 10.1002/jmv.25707. Epub 2020 Mar 3.
citation: Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775.
citation: Thorlund K, Dron L, Park J, Hsu G, Forrest JI, Mills EJ. A real-time dashboard of clinical trials for COVID-19. Lancet Digit Health. 2020 Jun;2(6):e286-e287. doi: 10.1016/S2589-7500(20)30086-8. Epub 2020 Apr 24. No abstract available.
citation: Yuen KS, Ye ZW, Fung SY, Chan CP, Jin DY. SARS-CoV-2 and COVID-19: The most important research questions. Cell Biosci. 2020 Mar 16;10:40. doi: 10.1186/s13578-020-00404-4. eCollection 2020.