Passive Immunotherapy In Patients With SARS CoV-2 (CoV-PlasGal)

PHASE II Clinical Trial Randomized And Controlled To Assess Need Of Oxygen On Day 14 After Administration Of Passive Immunotherapy In Patients Infected By SARS-CoV-2 With Risks Factors For Severe Disease

Plasma from convalescent individuals (convalescent plasma, CP) has been used for more than a hundred years for the treatment of infectious diseases. Among patients with COVID-19, it has been used first, in patients with severe infection. Although it is a safe treatment, it has not been possible to demonstrate a reduction in mortality in cases of acute respiratory distress syndrome.

The objective of the clinical trial is to evaluate the efficacy and safety of the early use (less than 5 days of symptoms) of CP in patients infected with SARS-CoV-2 with risk factors for severe disease.

The primary efficacy endpoint was the proportion of patients requiring oxygen therapy to maintain saturation >93% on day 14. Secondary objectives included, evaluation of the safety of the treatment, measured as the appearance of some adverse event related to the CP infusion; the evolution of COVID-19 symptoms and WHO progression scale status at day 14 and 28 after inclusion; the need for hospitalization due to progression of COVID-19. COVID-19 progression was considered as worsening of respiratory symptoms requiring oxygen therapy at some point. Finally, death from any cause was evaluated at 28 days, after inclusion in the study.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Vigo, Spain, 36211
    • Hospital Alvaro Cunqueiro

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:

Patients with SARS-CoV-2 infection, confirmed by any validated microbiological technique, and with one or more symptoms associated with COVID-19 with ≤5 days of evolution and with an oxygen saturation ≥93% breathing room air.

In addition, the patients had to present some risk factor for severe disease:

• Chronic heart failure (NYHA ≥ 2)
• Arterial hypertension under pharmacological treatment
• Chronic lung disease: COPD (bronchitis, emphysema or chronic obstruction) with dyspnoea at least on moderate exertion, or moderate-severe asthma (that required inhaled corticosteroids to control symptoms or had received systemic corticosteroids during the last year due to decompensation)
• Chronic renal failure (glomerular filtration rate <60 ml/min/1.73 m², by CKD- ILD)
• Diabetes mellitus requiring pharmacological treatment or obesity grade ≥ I (BMI ≥30 Kg/m2).
• Patients ≥65 years were included, regardless of other risk factors.

Exclusion Criteria:

• Duration of symptoms >5 days
• Dyspnoea at rest
• Need for supplemental oxygen to maintain O2 saturation >93%
• Solid neoplastic or haematologic disease (except skin cancer) with active treatment in the last 3 months before the onset of symptoms
• Patients under chronic corticosteroid treatment (equivalent to prednisone 10 mg/d for at least 28 days) or immunosuppressive treatment
• Decompensated liver cirrhosis
• Participation in another clinical trial
• History of hypersensitivity to haematological derivatives
• Pregnancy or lactation,
• AST/ALT >5 times the upper limit of normal or at baseline in patients with chronic liver disease
• Any condition that in the opinion of the investigator limits participation in the study.
• Patients who had received monoclonal antibodies against SARS-CoV-2

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: Convalescent plasma	Biological: Convalescent plasma; Admistration of one unit of convalescent plasma
No Intervention: Conventional treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Requirement for oxygen therapy to maintain saturation >93%	Proportion of patients that need oxygen to achieve a saturation >93%	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the treatment with CP	Safety of CP treatment was evaluated by the appearance of any adverse event related to the infusion	Day 1
Evolution of COVID-19 symptoms	Proportion of patients with 1+2 WHO progression scale. This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity.; = Not hospitalized without limitation in activity (no symptoms); = Not hospitalized with limitation in activity (continued symptoms); = Hospitalized not on supplemental oxygen; = Hospitalized on supplemental oxygen by mask or nasal prongs; = Hospitalized on non-invasive ventilation or high flow nasal cannula; = Hospitalized, intubated and mechanically ventilated; = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy); = Death	Day 14 and 28
Requirement for hospitalization due to worsening of symptoms	Worsening of symptoms was evaluated using the WHO progression scale; = Not hospitalized without limitation in activity (no symptoms); = Not hospitalized with limitation in activity (continued symptoms); = Hospitalized not on supplemental oxygen; = Hospitalized on supplemental oxygen by mask or nasal prongs; = Hospitalized on non-invasive ventilation or high flow nasal cannula; = Hospitalized, intubated and mechanically ventilated; = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy); = Death	Until day 28

Collaborators and Investigators

• Sponsor: Fundacin Biomedica Galicia Sur
• Collaborators: Health Knowledge Agency

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: September 17, 2022
• First Submitted That Met QC Criteria: October 5, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: CoV-PlasGal

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