Convalescent Plasma for Treating Patients With COVID-19 Pneumonia Without Indication of Ventilatory Support

Efficacy and Safety of Using Convalescent Plasma for Treating Patients With COVID-19 Pneumonia Without Indication of Ventilatory Support

The COVID-19 pandemic has been spreading continuously, and in Brazil, until August 18, 2020, there have been more than 3,359,000 cases with more than 108,536 deaths, with daily increases. The present study proposes to evaluate the efficacy and safety of using convalescent plasma for treating patients with COVID-19 pneumonia without indication of ventilatory support.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: Convalescent plasma

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eduardo M Rego, MD, PhD; Phone Number: 55 16 981110090; Email: edumrego@hotmail.com
• Study Contact Backup: Name: Abel Costa Neto, MD; Phone Number: 55 11 964999091; Email: abel.neto@oncologiador.com.br

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Recruiting
    • D'Or Institute for Research and Education
    • Contact: Eduardo M Rego, MD, PhD
    • Principal Investigator: Eduardo M Rego, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Recipient Inclusion Criteria:

• Confirmed diagnosis of COVID-19 by RT-PCR;
• Time between symptom onset and inclusion ≤ 7 days;
• Chest tomography with <50% involvement of the lung parenchyma;
• No indication of ventilatory support at the time of randomization;
• Sign the consent form.

Recipient Exclusion Criteria:

• Contraindication to transfusion or history of previous reactions to blood products for transfusion;
• Pregnant women;
• Limiting comorbidity for administering the therapies provided for in this protocol in the opinion of the investigator.

Donor Inclusion Criteria for Plasmapheresis:

• Convalescent plasma donation will be eligible for patients ≥ 18 years old who had previously confirmed COVID-19 by RT-PCR, which met the criteria adopted by technical notes n13 and 21/2020-CGSH/DAET/SAES/MS;
• SARS-COV-2 negative RT-PCR;
• Asymptomatic for at least 14 days;
• SARS-CoV-2 anti-peak titre with dilution ≥ 1: 320;
• Sign the consent form.

Donor Exclusion Criteria:

• Female gender with previous pregnancy;
• Absence of peripheral venous network compatible with the apheresis procedure;
• Positive or indeterminate result in any of the infectious screening tests;
• Presence of intellectual incapacity to understand the guidelines regarding the risks and benefits of participating in the study.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment; Participants will receive the standard treatment
Experimental: Convalescent Plasma + Standard treatment; Participants will receive the standard treatment and convalescent plasma	Biological: Convalescent plasma; The intervention group will receive 400 mL of convalescent plasma with a SARS-CoV-2 antispike antibody titer with a dilution ≥ 1: 320.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve of SARS-COV-2 viral load obtained from nasopharyngeal and /or oropharyngeal swabs.	To evaluate the area under the curve of SARSCoV-2 viral load in nasopharyngeal and or oropharyngeal samples on days 0, 3, 6, 9, 12, 15, 18 and 15 after randomization.	0, 3, 6, 9, 12, 15, 18 and 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of clinical improvement using an Ordinal Severity Scale	The seven-point scale is as follows: Death 7 points;; Hospital admission for mechanical ventilation plus additional organ support (eg, pressors, RRT, ECMO) = 6 points;; Hospital admission for mechanical ventilation = 5 points;; Hospital admission for non-invasive ventilation or high-flow oxygen therapy = 4 points;; Hospital admission for oxygen therapy (but not requiring high-flow or non-invasive ventilation) = 3 points;; Hospital admission but not requiring oxygen therapy = 2 points;; Discharged with limitations of activities = 1 point;; Discharged with no limitations of activities = 0 point;	0, 7, 10, 14, 21 and 28 days
Evaluate oxygen saturation		0, 3, 6, 9, 12, 15, 18 and 21 days
Evaluate oxygen supplementation		0, 3, 6, 9, 12, 15, 18 and 21 days
Assess respiratory rate		0, 3, 6, 9, 12, 15, 18 and 21 days
Evaluate the PaO2 / FiO2 ratio (for patients on mechanical mechanisms)		0, 3, 6, 9, 12, 15, 18 and 21 days
Length of hospital stay		21 days
Length of stay in intensive care		21 days
Assess the rate of orotracheal intubation		21 days
Change in the profile of cytokines/chemokines in both groups	Quantification by ELISA the levels of 36 molecules determined simultaneously using the Human Cytokine Array Kit da R&D Systems (C5a, IL-4, IL-32 alpha, CD40 ligand, IL-5, CXCL10 / IP-10, G-CSF, IL-6, CXCL11 / I-TAC, GM-CSF, IL-8, CCL2 / MCP-1, CXCL1 / GRO alpha, IL-10, MIF, CCL1 / I-309, IL-12 p70, CCL3 / MIP-1 alpha, ICAM-1, IL-13, CCL4 / MIP-1 beta, IFN -gamma, IL-16, CCL5 / RANTES, IL-1 alpha, IL-17, CXCL12 / SDF-1, IL-1 beta, IL-17E, Serpin E1 / PAI-1, IL-1ra, IL-23, TNF-alpha, IL-2, IL-27 and TREM-1)	0, 3, 6, 9, 12, 15, 18 and 21 days
Presence of antibodies against SARS-CoV-2 in serum after convalescent plasma administration		0, 3, 6, 9, 12, 15, 18 and 21 days
Death rate		7, 10, 14, 21 and 28 days
Rate of transfusion reactions to convalescent plasma infusion		21 days

Collaborators and Investigators

• Sponsor: D'Or Institute for Research and Education
• Collaborators: Hospital do Coracao
• Investigators: Principal Investigator: Eduardo M Rego, MD, PhD, D'Or Institute for Research and Education

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2020
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): January 30, 2022

Study Registration Dates

• First Submitted: August 19, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 6, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; 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; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: 34651120.8.0000.5249

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
• product manufactured in and exported from the U.S.: No