Hyperimmune Convalescent Plasma in Moderate and Severe COVID-19 Disease

Randomized, Open Label, Prospective Study of the Safety and Efficacy of Hyperimmune Convalescent Plasma in Moderate and Severe COVID-19 Disease

The clinical trial aims to study the safety and efficacy of transfusion of COVID-19 convalescent hyperimmune plasma for the treatment of moderate and severe forms of COVID-19 disease in comparison with non-convalescent fresh frozen plasma (standard plasma).

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: COVID-19 convalescent hyperimmune plasma; Biological: Non-convalescent fresh frozen plasma (Standard plasma)

Detailed Description

This is a study of the safety and efficacy of the use of COVID-19 convalescent plasma (from subjects who have recovered from SARS-CoV-2) in the treatment of moderate and severe forms of the SARS-CoV-2 infection. Currently, there are no registered drugs for the treatment of the SARS-CoV-2 infection in the world. The use of hyperimmune plasma is a well-known method used for many decades to treat many dangerous infections. The effectiveness of such a therapy for COVID-19 patients has recently been demonstrated in a number of clinical studies in China. Therefore, we plan to study the feasibility of administering multiple doses of COVID-19 convalescent plasma in comparison with standard plasma to moderate and severe patients with COVID-19.

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

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115682
    • Federal Research Clinical Center of Federal Medical & Biological Agency

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women aged 18-75 years.
2. The presence of COVID-19 infection, confirmed by PCR testing
3. The presence of the COVID-19 pneumonia pattern on the chest HRCT with a damage to more than 25% of the lung parenchyma
4. Morning fever ≥ 38.0 °C over the last three days
5. CRP blood level ≥ 50 mg / ml or ferritin blood level ≥ 600 μg / ml
6. A signed informed consent

Exclusion Criteria:

1. Respiratory index ≤200
2. Contraindications for the transfusion of donor immune plasma or history of prior reactions to blood transfusions
3. Mechanical ventilation
4. The presence of chronic lung diseases with chronic respiratory failure.
5. The need for home continuous oxygen therapy before the onset of current disease.
6. Serum creatinine level higher than 150 μmol / l
7. Pregnancy or breastfeeding

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: COVID-19 convalescent hyperimmune plasma; Moderately and severely ill COVID-19 patients treated with convalescent hyperimmune plasma. Patients will be infused with two units of 300 ml	Biological: COVID-19 convalescent hyperimmune plasma; Subjects to receive double convalescent hyperimmune plasma units of 300 ml each, with the 2nd unit administered no later than 24 hrs after the first one
Placebo Comparator: Non-convalescent fresh frozen plasma (Standard plasma); Moderately and severely ill COVID-19 patients treated with non-convalescent fresh frozen plasma (standard plasma). Patients will be infused with two units of 300 ml	Biological: Non-convalescent fresh frozen plasma (Standard plasma); Subjects to receive double standard plasma units of 300 ml each, with the 2nd unit administered no later than 24 hrs after the first one

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number and proportion of patients with the normal body temperature (≤37.2 C) at the day 1, 2, 3, 4, 5, 6, 7 after the start of therapy	The number and proportion of patients with the normal body temperature (≤37.2 C) at the days 1, 2, 3, 4, 5, 6, 7 after the start of therapy, for the statistical data comparison between the two arms.	Days 1, 2, 3, 4, 5, 6, 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days before mechanical ventilation	For each patient, the number of days passed from the plasma administration to placing on mechanical ventilation will be noted, for the statistical data comparison between the two arms.	30 days
Days of need for oxygen therapy	For each patient, the number of days he or she spent on the oxygen support after the plasma administration will be noted, for the statistical data comparison between the two arms.	30 days
Days of stay in the ICU	For each patient, the entire duration of ICU stay after the plasma administration will be noted, for the statistical data comparison between the two arms.	30 days
Days of hospitalization	For each patient, the entire duration of hospital stay after the plasma administration will be noted, for the statistical data comparison between the two arms.	30 days
Changes of the titer of the SARS-CoV-2 antibodies in the blood plasma of patients	Changes of the plasma levels of the SARS-CoV-2 antibodies, days 14 and 30 after the treatment start vs those levels before the treatment start (day 0) for the same patients.	Days 0, 14, 30
Dynamics of the cytokine profile	Changes of the plasma levels of IL2, IL6, IL10, TNFalpha and INFgamma, days 3 and 7 after the treatment start vs those levels before the treatment start (day 0) for the same patients.	Days 0, 3, 7
Incidence of the cytokine storm development and the need of administering cytokine storm inhibitors	Incidence of administering IL6 receptor blockers (tocilizumab, sarilumab)	Days 3, 7
Dynamics of the level of C-reactive protein	Changes of the plasma levels of C-reactive protein, days 1, 2, 3, 4, 5, 6, 7 after the treatment start vs those levels before the treatment start (Day 0) for the same patients.	Days 0, 1, 2, 3, 4, 5, 6, 7
30-day mortality rate	30-day mortality rate, for the statistical data comparison between the two arms.	30 days

Collaborators and Investigators

• Sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia
• Investigators: Principal Investigator: Alexander V Averyanov, MD, PhD, Federal Pulmonology Scientific and Research Institute, FMBA of Russia; Study Director: Vladimir P Baklaushev, MD, PhD, Federal Research Clinical Center, FMBA of Russia

Publications and helpful links

General Publications

• Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub4.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): July 10, 2020
• Study Completion (Actual): September 23, 2020

Study Registration Dates

• First Submitted: May 13, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• 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: CovPlas-Covid19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no current plan to share individual participant data (IPD).

Drug and device information, study documents

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