Treatment of Patients With COVID-19 With Convalescent Plasma (COOPCOVID-19)

Treatment of Patients With COVID-19 With Convalescent Plasma Transfusion: a Multicenter, Open-labeled, Randomized and Controlled Study

The COVID-19 pandemic has been spreading continuously, and in Brazil, until May 31, 2020, there have been more than 450.000 cases with more than 28.000 deaths, with daily increases. The present study proposes to evaluate the efficacy and safety of convalescent plasma in treatment of severe cases of COVID-19 in a multicenter, randomized, open-label and controlled study

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: convalescent plasma

Detailed Description

Eligible patients will be randomized 1:1:1 into 3 treatment groups: A- standard (control); B- standard and convalescent plasma in a volume of 200ml (150-300ml); C- standard and convalescent plasma in a volume of 400ml (300-600ml). The Bayesian multi-arm and multi-stage model will be used, which will allow an interim analysis after the inclusion of 30 patients, with repeated interim analyses for every 30 additional patients. With this, we expect to define not only the efficacy of convalescent plasma, but also the volume of plasma needed if efficacy is proven. The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 01403-002
      • University of Sao Paulo - General Hospítal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age = or > than 18 years; .
• Laboratory-proven COVID-19 infection by RT-PCR in any clinical sample . Time since symptom onset less than 10 days at the time of screening; - . Presence of COVID-19 pneumonia, with a typical, indeterminate or atypical compatible image in a chest tomography exam (see definition below) -
• Presence of one of the following criteria:
• Need for> 3L of O2 in the catheter / mask or> 25% in the Venturi mask to maintain O2 saturation> 92% B presence of respiratory distress syndrome with PaO2 / FiO2 <300mmHg If intubated, within 48 hours of orotracheal intubation
• Absence of a history of serious adverse reactions to transfusion, for example, anaphylaxis; - .Participation approval by the research clinician

Exclusion Criteria:

• Already enrolled in another clinical trial evaluating antiviral or immunobiological therapy for the treatment of COVID-19.
• IgA deficiency
• Presence of a clinical condition that does not allow infusion of 400 ml of volume at clinical discretion
• Pregnancy or breastfeeding
• Receipt of immunoglobulin in the last 30 days
• Presence of significant risk of death within the next 48 hours at clinical discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Group A; Participants will receive the standard of care treatment	Biological: convalescent plasma; The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.
Active Comparator: Group B; Participants will receive the standard treatment and convalescent plasma in a volume of 200ml (150-300ml)	Biological: convalescent plasma; The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.
Active Comparator: Group C; Participants will receive the standard treatment and convalescent plasma in a volume of 400ml (300-600ml)	Biological: convalescent plasma; The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time elapsed until clinical improvement or hospital discharge	clinical improvement is defined as the time from the randomization date until the decline of 2 categories on the ordinal scale of 10 categories or hospital discharge (whichever comes first)	Follow up until 28 days after transfusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acute adverse events	incidence of acute adverse events possibly or definitively realted to convalescent plasma transfusion	Up to 12 hours after transfusion
Clinical Status	Evaluation according to an ordinal scale of 10 categories	"Day 7", "Day 14" and "Day 28"
Duration of clinical events	Duration of mechanical ventilation, length of hospital stay in survivors up to 28 days and time from the beginning of treatment to death	Up to 28 days
SARS-CoV-2 in nasopharyngeal swab	Detection of SARS-CoV-2 in nasopharyngeal swab	Days 0, 1, 3, 7, 14 and 28 after transfusion and control groups
IgG, IgM and IgA titers for SARS-CoV-2	Specific IgG, IgM and IgA titers for SARS-CoV-2	Days 0, 1, 3, 5, 7, 14 and 28 after transfusion and control groups
Neutralizing antibodies	Titers of neutralizing antibodies	0,1,7 14 and 28 days after transfusion and control groups

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Hospital Israelita Albert Einstein; Hospital Sirio-Libanes; Hospital Ernesto Dornelles; Faculty of Medicine of Ribeirão Preto (FMRP-USP); Ministério da Ciência, Tecnologia, Inovações e Comunicações; Hospital de Clínicas, Faculdade de Medicina Universidade Estadual de Campinas; Grupo Hospitalar Conceição
• Investigators: Principal Investigator: Esper G Kallás, PhD, MD, University of Sao Paulo General Hospital

Publications and helpful links

General Publications

• Song ATW, Rocha V, Mendrone-Junior A, Calado RT, De Santis GC, Benites BD, Costa-Lima C, Vargas T, Marques LS, Fernandes JC, Breda FC, Wendel S, Fachini R, Rizzo LV, Kutner JM, Avelino-Silva VI, Machado RRG, Durigon EL, Chevret S, Kallas EG. Treatment of severe COVID-19 patients with either low- or high-volume of convalescent plasma versus standard of care: A multicenter Bayesian randomized open-label clinical trial (COOP-COVID-19-MCTI). Lancet Reg Health Am. 2022 Jun;10:100216. doi: 10.1016/j.lana.2022.100216. Epub 2022 Mar 15.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): February 15, 2022

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): May 19, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: safety; COVID-19; efficacy; convalescent plasma
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COOP-COVID-19-MCTIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No