Statistical and Epidemiological Study Based on the Use of Convalescent Plasma for the Management of Patients With COVID-19 (PROMETEO)

Pilot Clinical, Statistical and Epidemiological Study on Efficacy and Safety of Convalescent Plasma for the Management of Patients With COVID-19

The health contingency established against the Severe Acute Respiratory Syndrome associated type 2 Coronavirus (SARS-CoV-2) has promoted a race against the clock for the search on treatment against the disease related with coronavirus (COVID-19). There are no current approved therapeutic options against the virus, although there is a rush for the development of drugs, vaccines and even the passive immunization through plasma from convalescent patients. This passive immunization is made with the administration of antibodies from patients that went through the infectious state of the disease and progress to clinical remission.

SARS-CoV-2, and its predecessor SARS-CoV-1, have great similarities between their genes and proteins; tis allow to hypothesize that the antibodies developed against SARS-CoV1 can recognize the antigens of SARS-CoV-2. In this manner, the transfusion of convalescent plasma to patients with the infection brings the probability on eliminating the infection, in this case SARS-CoV-2. There are evidence of this phenomenon observed in previous pandemics caused by SARS-CoV-1, Influenza AH1N1 and Ebola virus.

The objective of the study is to develop a therapeutic strategy based on the administration of plasma from patients with COVID-19 with clinical remission to patients that are coursing with the infection. The expected results hopes to establish an effective treatment and satisfactory recovery of patients with COVID-19. Also, we expect to describe the respective antibodies related against the SARS-CoV-2 infection.

Study Overview

• Status: Unknown
• Conditions: COVID-19 Pneumonia; Convalescent Plasma
• Intervention / Treatment: Biological: Convalescent plasma

Detailed Description

The health contingency established against the Severe Acute Respiratory Syndrome associated type 2 Coronavirus (SARS-CoV-2) has promoted a race against the clock for the search on treatment against the disease related with coronavirus (COVID-19). There are no current approved therapeutic options against the virus, although there is a rush for the development of drugs, vaccines and even the passive immunization through plasma from convalescent patients. This passive immunization is made with the administration of antibodies from patients that went through the infectious state of the disease and progress to clinical remission.

SARS-CoV-2, and its predecessor SARS-CoV-1, have great similarities between their genes and proteins; tis allow to hypothesize that the antibodies developed against SARS-CoV1 can recognize the antigens of SARS-CoV-2. In this manner, the transfusion of convalescent plasma to patients with the infection brings the probability on eliminating the infection, in this case SARS-CoV-2. There are evidence of this phenomenon observed in previous pandemics caused by SARS-CoV-1, Influenza AH1N1 and Ebola virus.

The objective of the study is to develop a therapeutic strategy based on the administration of plasma from patients with COVID-19 with clinical remission to patients that are coursing with the infection. The expected results hopes to establish an effective treatment and satisfactory recovery of patients with COVID-19. Also, we expect to describe the respective antibodies related against the SARS-CoV-2 infection.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Coahuila
    • Saltillo, Coahuila, Mexico, 25000
      • Hospital Universitario "Dr. Gonzalo Valdes Valdes"

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 (Donors):

• Signed informed consent
• At least positive for 1 q-PCR test for SARS-CoV-2
• 14 days of COVID-19 clinical remission
• Positive serologic test for SARS-CoV-2
• Requirements to donate according to NOM-253-SSA1-2012
• To accept sample storing for future study

Inclusion Criteria (Receptors):

• Signed informed consent provided by the patient, legal guardian or the health provider if not available
• Patients hospitalized in an ICU dedicated to the treatment of COVID-19 patients
• At least positive for 1 q-PCR test for SARS-CoV-2
• Patients with COVID-19 defined as severe or critically ill:

Severe: RF > 30 bpm, oxygen saturation <94%, Pa/FiO2 <301, bilateral lung infiltrates that extends in >50% (by chest radiograph or CT scan) in 24-48 hours Critically ill: Respiratory failure (PaO2 <60 mmHg or SatO2 <90% with FiO2 >60%) and septic shock (MAP <65 mmHg with vasoactive requirement, lactate > 2 mmol/L and SOFA score >1)

Exclusion Criteria:

• Positive pregnancy test
• Patients in lactation
• Informed consent not signed
• Patients involved in other treatment protocols
• Patients on immunomodulatory drugs (DMARDs, monoclonal antibodies or smal molecule drugs)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Convalescent plasma; Best available treatment + convalescent plasma Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Plasma will be split by aliquots of 200 ml for its storage on -60 celsius degrees until it's used. After defrosting, it will be administered on 2 200 ml separated doses on a 12 hours interval.	Biological: Convalescent plasma; Best available treatment + convalescent plasma Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Plasma will be split by aliquots of 200 ml for its storage on -60 celsius degrees until it's used. After defrosting, it will be administered on 2 200 ml separated doses on a 12 hours interval.
Placebo Comparator: Best available treatment; Best available treatment + Placebo (0.9% saline solution) Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Placebo will consist on 2 doses of 200 ml of 0.9% saline solution separated on a 12 hour interval.	Biological: Convalescent plasma; Best available treatment + convalescent plasma Best available treatment: hemodynamic support, oxygen supplementation, antibiotic therapy (if required), and individualized treatment judged by the attending physician. Plasma will be split by aliquots of 200 ml for its storage on -60 celsius degrees until it's used. After defrosting, it will be administered on 2 200 ml separated doses on a 12 hours interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Any cause mortality during the first 30 days of treatment	30 days
Side effects	Side effects associated with the administration of convalescent plasma	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in Intensive Care Unit (ICU)	Time to discharge from the ICU	14 days
Length of stay in hospitalization	Time for discharge from hospital	21 days
Days of mechanical ventilation	Number of days with ventilatory support	14 days
Inflammatory biomarkers (d-dimer)	change in D-dimer (micrograms/L)	21 days
Inflammatory biomarkers (c-reactive protein)	change in C-reactive protein (milligrams/dL)	21 days
Inflammatory biomarkers (lactate dehydrogenase)	Change in LDH (UI/L)	21 days
Inflammatory biomarkers (ferritin)	Change in ferritin (nanograms/mL)	21 days

Collaborators and Investigators

• Sponsor: Universidad Autonoma de Coahuila
• Collaborators: National Council of Science and Technology, Mexico

Study record dates

Study Major Dates

• Study Start (Anticipated): July 6, 2020
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: COVID-19; Convalescent plasma; plasmapheresis
• 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: HUS-001/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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