Convalescent Plasma Therapy for Hospitalized Patients With COVID-19

Validation Protocol for The Clinical Use of Convalescent Plasma for Hospitalized Patients With COVID-19. A Prospective Study at a Hospital in Southern Brazil.

Plasma from donors who have recovered from coronavirus disease 2019 (COVID-19) contain antibodies to SARS-CoV-2 and may be a potential therapy for hospitalized patients with COVID-19. The efficacy of high-titer convalescent plasma for COVID-19, however, still unclear. The present study aims to evaluate the efficacy and safety of using convalescent plasma for treating hospitalized patients with COVID-19.

Study Overview

• Status: Completed
• Conditions: Coronavirus Infections; Respiratory Tract Diseases; COVID-19; Pneumonia; SARS-CoV-2; Convalescent Plasma
• Intervention / Treatment: Biological: Convalescent plasma; Drug: Standard of care

Detailed Description

This is an open-label, randomized controlled trial aimed to evaluate the efficacy and safety of using convalescent plasma for treating hospitalized patients with COVID-19. Participants must be adult hospitalized patients with a confirmed diagnosis of COVID-19 and time Between symptom onset and inclusion ≤ 7 days. Two hundred participants will be randomized in a 1:1 ratio to receive either 200-400 mL of high-titer COVID-19 convalescent plasma or standard care. The primary endpoint is the proportion of patients with clinical improvement at day 14 following randomization, defined by an increase of two points in the 7-point ordinal scale based on that recommended by the World Health Organization. Safety will be daily assessed by monitoring the occurrence of adverse effects and reactions to convalescent plasma transfusion. Study visits will occur on Day 1, Day 3, Day 7, and Day 14 or until hospital discharge, whichever comes first.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tânia P Costa, Master; Phone Number: +55 41 3136-2515; Email: tania.p@hospitaldorocio.com.br
• Study Contact Backup: Name: Leandro B Agati, PhD; Phone Number: +55 11 4040-8670; Email: agati@svriglobal.com

Study Locations

• Brazil
  • Paraná
    • Campo Largo, Paraná, Brazil, 83606-177
      • Maternidade e Cirurgia Nossa Senhora do Rocio/ SA - Hospital do Rocio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hospitalized patients aged ≥18 years.
• Confirmed diagnosis of COVID-19 by RT-PCR or antigen test in respiratory samples.
• Time between symptom onset and inclusion ≤ 7 days.
• Enrolled within 5 days of hospitalization.
• Sign the consent form.

Exclusion Criteria:

• Contraindication to transfusion due to inability to tolerate additional fluid, such as due to decompensated congestive heart failure.
• History of previous severe allergic reactions to transfused blood products.
• Limiting comorbidity for administering the therapies provided for in this protocol in the opinion of the investigator.
• Not currently enrolled another interventional clinical trial of COVID-19 treatment.
• Critically ill patient with COVID-19 being treated in intensive care.

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; The investigational product is anti-SARS-CoV-2 convalescent plasma obtained from former patients identified as having recovered from COVID-19 and obtained by Centro de Hematologia e Hemoterapia do Paraná - Hemepar following national blood donation guidelines and Brazilian Health Regulatory Agency (ANVISA) criteria. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined. Participants will receive the standard of care treatment and a single unit of convalescent plasma (volume=200 mL or 400 mL).	Biological: Convalescent plasma; The intervention group will receive 200 or 400 mL of high-titer COVID-19 convalescent plasma, ABO compatible with the patient, within 24 hours of randomization.
Active Comparator: Standard of care; Standard of care treatment according to the institutional protocol.	Drug: Standard of care; The active comparator group will receive oxygen supplementation, corticoids, antiretrovirals, and/or monoclonal antibodies according to the institutional protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status on a 7-point ordinal scale	Patients' clinical status over time assessed by a 7-point ordinal scale from World Health Organization (WHO). Lower scores are seen with better clinical outcomes. The scale categories are as follows: (1), not hospitalized with resumption of normal activities; (2), not hospitalized, but unable to resume normal activities; (3), hospitalized, not requiring supplemental oxygen; (4), hospitalized, requiring supplemental oxygen; (5), hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; (6), hospitalized, requiring ECMO (extracorporeal membrane oxygenation), IMV (intermittent mandatory ventilation), or both; (7), death. Proportion of patients with clinical improvement, defined by an increase of two points in the ordinal scale of seven WHO categories.	From randomization to end of study at Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants at each clinical status on a 7-point ordinal scale	Measure of patients' clinical status using an ordinal scale for clinical improvement created by World Health Organization (WHO) and based on 7-point scale categories. Lower scores in this scale are seen with better clinical outcomes. The scale categories are as follows: (1), not hospitalized with resumption of normal activities; (2), not hospitalized, but unable to resume normal activities; (3), hospitalized, not requiring supplemental oxygen; (4), hospitalized, requiring supplemental oxygen; (5), hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; (6), hospitalized, requiring ECMO, IMV, or both; (7), death.	Day 1, Day 3, Day 7, and Day 14 after randomization
Oxygen saturation		Day 1, Day 3, Day 7, and Day 14 after randomization
Prevalence of oxygen-intake methods	Percentage of participants using oxygen by mask or nasal prongs, oxygen by non-invasive ventilation or high flow, intubation & mechanical ventilation and ECMO.	Day 1, Day 3, Day 7, and Day 14 after randomization
Respiratory rate		Day 1, Day 3, Day 7, and Day 14 after randomization
The PaO2 / FiO2 ratio (for patients on mechanical mechanisms)		Day 1, Day 3, Day 7, and Day 14 after randomization
Number and /or extension of affected lung areas on chest computed tomography		Day 1, Day 3, Day 7, and Day 14 after randomization
Length of hospital stay		Day 1, Day 3, Day 7, and Day 14 after randomization
Length of stay in intensive care		Day 1, Day 3, Day 7, and Day 14 after randomization
Time until independence from oxygen therapy in days		Day 1, Day 3, Day 7, and Day 14 after randomization
Ventilator free days		Day 1, Day 3, Day 7, and Day 14 after randomization
In patients who needed mechanical ventilation, time to initiate mechanical ventilation (calculated in days, from entry into the protocol until orotracheal intubation)		Day 1, Day 3, Day 7, and Day 14 after randomization
Rate of transfusion reactions to convalescent plasma infusion		Daily, until Day 14 after randomization
Percentage of participants who develop serious adverse events and adverse events considered as definitely or probably associated with plasma transfusion	Adverse events (worsening anemia, urticaria, skin rash, transfusion-associated circulatory overload, and others) assessed during hospitalization.	Daily, until Day 14 after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between the presence of comorbidities at baseline and clinical status on a 7-point ordinal scale	Association between patients' clinical status assessed by a 7-point ordinal scale from World Health Organization (WHO) on Day 14 after randomization and baseline characteristics and history or comorbidities known at high risk for COVID-19 (age, sex, obesity - body mass index >30 kg/m², history of hypertension, chronic heart disease, congestive heart failure, chronic bronchopulmonary disease, diabetes mellitus, and immunosuppression). Lower scores in this scale are seen with better clinical outcomes. The scale categories are as follows: (1), not hospitalized with resumption of normal activities; (2), not hospitalized, but unable to resume normal activities; (3), hospitalized, not requiring supplemental oxygen; (4), hospitalized, requiring supplemental oxygen; (5), hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; (6), hospitalized, requiring ECMO, IMV, or both; (7), death.	Day 1 and Day 14 after randomization
Association between the volume of convalescent plasma transfused and clinical status on a 7-point ordinal scale	Association between patients' clinical status assessed by a 7-point ordinal scale from World Health Organization (WHO) on Day 14 after randomization and the volume of a single unit of convalescent plasma transfused (200 mL or 400 mL). Lower scores in this scale are seen with better clinical outcomes. The scale categories are as follows: (1), not hospitalized with resumption of normal activities; (2), not hospitalized, but unable to resume normal activities; (3), hospitalized, not requiring supplemental oxygen; (4), hospitalized, requiring supplemental oxygen; (5), hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; (6), hospitalized, requiring ECMO, IMV, or both; (7), death.	Day 1 and Day 14 after randomization
Changes from baseline in inflammatory surrogate markers: white blood counts, lymphocyte counts, C-reactive protein (CRP) and D-dimer levels		Day 1 and Day 14 after randomization
Association between the concentration of inflammatory surrogate markers and clinical status on a 7-point ordinal scale	Association between patients' clinical status assessed by a 7-point ordinal scale from World Health Organization (WHO) on Day 14 after randomization and inflammatory surrogate markers, which include white blood counts, lymphocyte counts, C-reactive protein (CRP) and D-dimer levels. Lower scores in this scale are seen with better clinical outcomes. The scale categories are as follows: (1), not hospitalized with resumption of normal activities; (2), not hospitalized, but unable to resume normal activities; (3), hospitalized, not requiring supplemental oxygen; (4), hospitalized, requiring supplemental oxygen; (5), hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation; (6), hospitalized, requiring ECMO, IMV, or both; (7), death.	Day 14 after randomization

Collaborators and Investigators

• Sponsor: Tânia Portella Costa
• Collaborators: Science Valley Research Institute; Centro de Hematologia e Hemoterapia do Paraná - Hemepar; Fundação Oswaldo Cruz, Instituto Carlos Chagas, ICC Paraná
• Investigators: Study Director: Kengi Itinose, MD, Maternidade e Cirurgia Nossa Senhora do Rocio/ SA - Hospital do Rocio

Publications and helpful links

General Publications

• Piechotta V, Chai KL, Valk SJ, Doree C, Monsef I, Wood EM, Lamikanra A, Kimber C, 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. 2020 Jul 10;7(7):CD013600. doi: 10.1002/14651858.CD013600.pub2.

Helpful Links

• Core Outcome Set (COS) for studies of any intervention in hospitalised patients with confirmed or suspected COVID-19

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2022
• Primary Completion (Actual): April 4, 2022
• Study Completion (Actual): April 7, 2022

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Respiratory Tract Diseases
• Other Study ID Numbers: CCP TRIAL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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