Convalescent Plasma for the Treatment of Severe SARS-CoV-2 (COVID-19)

Efficacy of Convalescent Plasma for the Treatment of Severe SARS-CoV-2 Infection: A Randomized, Open Label Clinical Trial

Convalescent plasma has been used for over 100 years in the treatment of severe acute respiratory infections of viral origin. There are not pharmacological treatments for the actual outbreak for SARS-Cov-2 and it is necessary to evaluate the efficacy of treatment options, including convalescent plasma transfusion. The hypothesis is that convalescent plasma is efficacious and safe for reducing mortality in patients with COVID-19 treated in ICU

Study Overview

• Status: Unknown
• Conditions: SARS-Cov-2
• Intervention / Treatment: Drug: Convalescent plasma

Detailed Description

Coronavirus infection has been declared by the World Health Organization as a pandemic. In addition to hemodynamic and ventilatory support in the intensive care unit, there is no treatment for COVID-19. Currently proposed treatments (chloroquine, antivirals, immunomodulators, among others) have low quality studies that do not prove efficacy.

Blood or plasma transfusion from convalescent patients (patients who have overcome the disease by generating a competent immune response) has been prescribed for over 100 years. In the last 15 years, convalescent plasma has been studied for the treatment of severe acute respiratory infections of viral origin, such as severe acute respiratory syndrome (SARS), avian influenza, and influenza A (H1N1). Suppressing viremia is one of the possible explanations for the efficacy of convalescent plasma treatment.

For the treatment of COVID-19, there are case series that show a clear improvement in severe patients after administration of convalescent plasma without significant adverse events. At the current crisis of the SARS-CoV-2 pandemic, in which there are no pharmacological treatments that have proven to have any therapeutic effect, it is imperative to assess the efficacy and safety of convalescent plasma transfusion in infected patients.

This is an open, randomized clinical trial with patient allocation in a 2 :1 ratio, plasma: standard management, for a superiority hypothesis. The main objective of this study is to determine the efficacy of convalescent plasma for the treatment of severe COVID-19 infection in terms of decreased in-hospital mortality.

• Study Type: Interventional
• Enrollment (Anticipated): 231
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Oliver G Perilla Suarez, Hematologist; Phone Number: +573136395608; Email: gerardoperilla@gmail.com
• Study Contact Backup: Name: Fabian A Jaimes Barragan, Epidemiol; Phone Number: +5742192420; Email: fabian.jaimes@udea.edu.co

Study Locations

• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia
      • Hospital San Vicente Fundación
      • Contact: Oliver Perilla, Hematologist; Phone Number: 3136395608; Email: gerardoperilla@gmail.com
      • Contact: Fabian Jaimes, Epidemiologi; Phone Number: 2192433; Email: fabian.jaimes@udea.edu.co

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:

For plasma donors:

• Over 18 years of age
• Men or nulliparous women with no history of recent abortions or transfusions SARS-CoV-2 infection by PCR in any sample or serological test with a maximum of 60 days from resolution of symptoms.
• If donation is done within 14 to 28 days after resolution of symptoms, the patient must have a negative PCR test for SARS-CoV-2. If donation is done after 28 days of resolving symptoms, no negative control test will be required.

For plasma recipients:

• Over 18 years of age
• SARS-CoV-2 infection confirmed by PCR in any sample
• Hospitalized in the ICU due to shock or respiratory failure, with less than 24 hours after entering the ICU.

Exclusion Criteria:

For plasma donors:

• Severe SARS-CoV-2 infections with an ICU requirement or those with asymptomatic infections will not be accepted as donors.
• Nor will a person who has received convalescent plasma as part of the COVID-19 treatment.

For plasma receivers:

• Serious volume overload or other condition that contraindicates plasma transfusion.
• History of anaphylaxis or serious adverse reaction to plasma.
• Previous diagnosis of immunoglobulin A deficiency

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
Experimental: Intervention group; Administration of two units of fresh frozen plasma (between 400 and 500 ml) obtained from convalescent patients from infection by SARS-CoV-2. Convalescent plasma is defined as the plasma of patients who had PCR confirmed SARS-CoV-2 infection, who have recovered clinically, and who have positive antibodies against SARS-CoV-2.	Drug: Convalescent plasma; 400-500ml convalescent plasma; Other Names: Plasma
No Intervention: Control group; Subjects assigned to the control group will receive support treatment in the intensive care unit based on institutional management guidelines. The use of antiviral, antimalarial or anti-inflammatory drugs is allowed in both groups according to the ICU protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrahospital mortality from any cause	Proportion of patients who die while being hospitalized	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Number of days hospitalized	Up to 60 days
Free time for ventilatory support on day 60	Number of days without ventilatory support	Day 60
Overall survival at day 60 since hospitalization	Proportion of patients alive on day 60	Day 60
Cumulative incidence of adverse events: transfusion reactions (fever, flare), TRALI (transfusion-associated lung injury), TACO (transfusion-related circulatory overload), transfusion- related infections	Proportion of adverse events related with convalescent plasma	Up to 28 days

Collaborators and Investigators

• Sponsor: Hospital San Vicente Fundación
• Collaborators: Hospital Pablo Tobón Uribe; Clínica León XIII; Grupo de Inmunodeficiencias primarias Universidad de Antioquia; Clínica Universitaria Bolivariana; Clínica Rosario El Tesoro; Clinica Las Americas; Clínica Cardiovid
• Investigators: Principal Investigator: Oliver Perilla Suarez, Hematologist, Hospital San Vicente Fundación

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Covid-19; Coronavirus; Intensive Care Unit; Convalescent plasma
• Other Study ID Numbers: 002 (University of CT Health Center)

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