Convalescent Plasma, Coronavirus Infections, COVID-19, Pneumonia, Respiratory Tract Diseases, SARS-CoV-2
Conditions
Brief summary
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.
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.
Interventions
BIOLOGICALConvalescent 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.
DRUGStandard of care
The active comparator group will receive oxygen supplementation, corticoids, antiretrovirals, and/or monoclonal antibodies according to the institutional protocol.
Sponsors
Centro de Hematologia e Hemoterapia do Paraná - Hemepar
Fundação Oswaldo Cruz, Instituto Carlos Chagas, ICC Paraná
Science Valley Research Institute
Tânia Portella Costa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label, randomized study design (1: 1), controlled trial, in hospitalized patients with COVID-19.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical status on a 7-point ordinal scale | From randomization to end of study at Day 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants who develop serious adverse events and adverse events considered as definitely or probably associated with plasma transfusion | Daily, until Day 14 after randomization | Adverse events (worsening anemia, urticaria, skin rash, transfusion-associated circulatory overload, and others) assessed during hospitalization. |
| 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 at each clinical status on a 7-point ordinal scale | Day 1, Day 3, Day 7, and Day 14 after randomization | 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. |
| Oxygen saturation | Day 1, Day 3, Day 7, and Day 14 after randomization | — |
| Prevalence of oxygen-intake methods | Day 1, Day 3, Day 7, and Day 14 after randomization | Percentage of participants using oxygen by mask or nasal prongs, oxygen by non-invasive ventilation or high flow, intubation & mechanical ventilation and ECMO. |
| 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 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Association between the volume of convalescent plasma transfused and clinical status on a 7-point ordinal scale | Day 1 and Day 14 after randomization | 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. |
| 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 | Day 14 after randomization | 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. |
| Association between the presence of comorbidities at baseline and clinical status on a 7-point ordinal scale | Day 1 and Day 14 after randomization | 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. |
Countries
Brazil
Outcome results
None listed