Safety and Efficacy of Convalescent Plasma Transfusion for Patients With COVID-19 (EPCOvid-1)

Phase 2b/3 Trial to Evaluate the Safety and Efficacy of Plasma Transfusion From Convalescent Patients With SARS-CoV-2 Infection on Severity and Mortality of COVID-19 in Hospitalized Patients.

This is a multicenter double blinded study to evaluate the efficacy and safety of convalescent plasma from COVID-19 recovered individuals to treat hospitalized patients with severe COVID-19 disease. The study will enroll 410 subjects who will be randomized 1:1 to receive convalescent plasma or normal saline solution in a blinded manner. The primary endpoint will be improvement on the 8 point WHO scale over 28 days. Mortality at day 28 will be a secondary endpoint. An interim analysis will be done when 224 patients have completed their follow up to assess safety and to indicate continuation or stopping of the study, based on safety and efficacy observed.

Study Overview

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

Detailed Description

A total of 410 patients with COVID 19 who fulfill inclusion criteria will be invited to receive:

Human convalescent plasma from recovered patients in two infusions of 200 ml separated with 24 to 72 hours or Normal saline solution in a similar plasma bag. Both products will be covered in an identical material to avoid identification of the infused product.

Primary endpoint:

Improvement on the 8 point WHO scale over 28 days.

Secondary endpoints.

Mortality at day 28

• Presence of antibodies against SARS-CoV-2 in serum on days 0, 3, 7, 14, 21 y 28 after plasma administration, as long as the patient remains in the hospital.
• Disease progression to a worse stage compared to the baseline on admission to the study according to SOFA scale.
• Disease progression to a worse stage defined as worsening in at least two categories in the OMS disease scale on different timelines in comparison to baseline on admission to the study
• Number of hours on mechanical ventilation in those who enter the study on mechanical ventilation.
• Number of days with fever defined as temperature >38°C on at least one occasion during the day

Inclusion criteria:

1. Adults older than 18 years.
2. Confirmed SARS-CoV2 infection
3. Patient hospitalized for COVID 19
4. Severe disease or risk for severe disease
5. Informed consent from patient or responsible person.

Exclusion criteria

1. History of allergic reactions to blood products
2. SOFA scale >12 points
3. Absolute contraindication for administration of plasma
4. Participation in other blinded clinical trial
5. Projected life expectancy less than 3 months
6. Any condition perceived by the investigator as not appropriate for participation of the patient in the trial.

• Study Type: Interventional
• Enrollment (Anticipated): 410
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Tlalpan
    • Mexico City, Tlalpan, Mexico, 14000
      • Recruiting
      • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
      • Contact: Juan Sierra Madero, MD; Phone Number: +525556559675; Email: jsmadero@yahoo.com

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:

1. Adults 18 years of age and older.
2. Confirmed SARS-CoV2 infection
3. Hospitalized for COVID 19
4. Severe disease or risk for severe disease
5. Informed consent from patient or responsible person.

Exclusion Criteria:

1. History of allergic reactions to blood products
2. SOFA scale >12 points
3. Absolute contraindication for administration of plasma
4. Participation in other blinded clinical trial
5. Projected life expectancy less than 3 months
6. Any condition perceived by the investigator as not appropriate for participation of the patient in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: convalescent plasma; Convalescent plasma obtained from volunteers who have recovered from COVID 19. Enclosed with a similar material as the control	Biological: convalescent plasma; Plasma obtained from volunteers who have recovered from SARS-Cov-2 infection. Two 200 ml infusions will be administered with 24-72 hours in between.
Placebo Comparator: Normal saline; Normal saline solution in 200 ml plasma bags enclosed with with a similar material as the plasma	Biological: convalescent plasma; Plasma obtained from volunteers who have recovered from SARS-Cov-2 infection. Two 200 ml infusions will be administered with 24-72 hours in between.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity and death	Ordinal 8-point severity outcome scale: 1 Death, 2 Hospitalized, intubated and receiving mechanical ventilation and additional organ support (eg. renal replacement therapy, vasopressors, extracorporeal membrane oxygenation), 3 Hospitalized, intubated and receiving mechanical ventilation but no additional organ support, 4 Hospitalized receiving non-invasive ventilation of high-flow oxygen, 5 Hospitalized, receiving supplementary oxygen by mask or nasal prongs, 6 Hospitalized, no oxygen therapy needed, 7 Not-hospitalized (ambulatory) with limited activity, 8 Not-hospitalized (ambulatory) with no limitation of activities.	28 days
Adverse events that require study treatment interruption	Any unfavorable and unintended symptom or sign (including an abnormal laboratory finding) temporally associated with the study intervention and considered related to the intervention that require interruption of study treatment. Including but not limited to: Severe allergic reactions (rash and fever), transfusion-associated lung injury (TRALI), transfusion-associated circulatory overload (TACO), and other severe unexpected events	During the 28 day of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to clinical improvement	Time (in days) to improvement in at least two categories in the 8-point ordinal severity scale in comparison to baseline on admission to the study.	28 days
Severity and death	Ordinal 8-point severity outcome scale: 1 Death, 2 Hospitalized, intubated and receiving mechanical ventilation and additional organ support (eg. renal replacement therapy, vasopressors, extracorporeal membrane oxygenation), 3 Hospitalized, intubated and receiving mechanical ventilation but no additional organ support, 4 Hospitalized receiving non-invasive ventilation of high-flow oxygen, 5 Hospitalized, receiving supplementary oxygen by mask or nasal prongs, 6 Hospitalized, no oxygen therapy needed, 7 Not-hospitalized (ambulatory) with limited activity, 8 Not-hospitalized (ambulatory) with no limitation of activities.	Days 1, 3, 5, 7, 12, 14, and 21.
Antibodies against SARS-CoV-2	Antibody titers on serum/plasma as long as the patient remains in the hospital.	Days 0, 3, 7, 14, 21, 28
Disease progression 1	Changes in SOFA scale during hospitalization compared to the baseline	28 days
Disease progression 2	Changes in at least two categories in the 8-point ordinal severity scale in comparison to baseline on admission to the study	Days 7,14, 21, 28
Time on mechanical ventilation	Time (in hours) spent receiving invasive mechanical ventilation in those who enter the study on mechanical ventilation.	28 days
Number of days with fever	Temperature >=38°C on at least one measurement during the day	28 days
Adverse events attributed to the study intervention	Any unfavorable and unintended symptom or sign (including an abnormal laboratory finding) temporally associated with the study intervention and considered related to the intervention.	28 days

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Collaborators: Hospital General Dr. Manuel Gea González; Instituto Nacional de Cardiologia Ignacio Chavez; Instituto Nacional de Cancerologia de Mexico; Instituto Nacional de Enfermedades Respiratorias; Hospital Regional de Alta Especialidad del Bajio; Hospital San Jose Tec de Monterrey
• Investigators: Principal Investigator: Juan G Sierra-Madero, MD, Department of Infectious Diseases

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Anticipated): November 30, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 26, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; randomized clinical trial; 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: 3380

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Plan to make IPD still not decided and would need approval by regulatory authorities

Drug and device information, study documents

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