Convalescent Plasma Therapy vs. SOC for the Treatment of COVID-19 in Hospitalized Patients
- Conditions
- COVID-19
- Interventions
- Drug: Standard of CareOther: Blood and derivatives.
- Registration Number
- NCT04345523
- Lead Sponsor
- Cristina Avendaño Solá
- Brief Summary
A total of 278 patients are planned.
All patients will be in an early-stage of COVID-19. They must be adults and hospitalized.
In this study, all participating patients will receive the standard treatment provided according to the current treatment protocols for coronavirus disease. In addition to this treatment, each patient will be randomly assigned to receive additional treatment with convalescent plasma transfusion (CP; blood plasma from patients who have been cured of coronavirus), or continue with standard treatment but without adding transfusion.
50% of the chances of additional treatment with CP, and 50% of the chances of receiving only the standard treatment for coronavirus.
The duration of the study shall be one month from the assignment of the treatment.
The patient and the doctor will know the treatment assigned.
- Detailed Description
A multi-center, randomized, clinical trial with two arms to study the efficacy and safety of passive immunotherapy with CP compared to a control of standard of care (SOC).
All trial participants will receive SOC:
* Treatment arm: Pathogen-reduced CP from patients recovered from COVID-19, whom, for the purpose of this trial, are herein designated as donors.
* Control arm: SOC for COVID-19.
Randomization among the two arms will be 1:1 and will be stratified per center. Of note, in the current status of a worldwide pandemic for which we have no approved vaccines or drugs, for the purpose of this trial SOC would also accept any drugs that are being used in clinical practice (e.g. lopinavir/ritonavir; darunavir/cobicistat; hydroxy/chloroquine, tocilizumab, etc.), other than those used as part of another clinical trial.
The study is planned with a sequential design. Interim analyses: comprehensive safety data monitoring analyses will be conducted when 20%, 40%, 60% and 80% of patients, or at the discretionary DSMB criteria when needed. A DSMB charter will be set before the trial initiation where criteria for prematurely stopping the trial due to safety issues will be set. Interim analyses will be predefined upfront based on the DSMB recommendations.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 350
-
Written informed consent prior to performing study procedures. Witnessed oral consent will be accepted in order to avoid paper handling. Written consent by patient or representatives will be obtained as soon as possible.
-
Male or female adult patient ≥18 years of age at time of enrolment.
-
Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR in naso/oropharyngeal swabs or any other relevant specimen in the ongoing COVID-19 symptomatic period. Alternative test (i.e antigenic tests) are also acceptable as laboratory confirmation if their adequate specificity has been accepted by the sponsor.
-
Patients requiring hospitalization for COVID-19 without mechanical ventilation (invasive or non-invasive) or high flow oxygen devices and at least one of the following:
- Radiographic evidence of pulmonary infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air that requires supplemental oxygen.
-
No more than 7 days between the onset of symptoms (fever or cough) and treatment administration day.
- Requiring mechanical ventilation (invasive or non-invasive) or high flow oxygen devices.
- More than 7 days since symptoms (fever or cough).
- Participation in any other clinical trial of an experimental treatment for COVID-19.
- In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments.
- Any incompatibility or allergy to the administration of human plasma.
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Arm Standard of Care Standard of Care (SOC) for COVID-19 Treatment Arm Blood and derivatives. Pathogen-reduced CP from patients recovered from COVID-19, whom, for the purpose of this trial, are herein designated as donors.
- Primary Outcome Measures
Name Time Method Category Changes in the "7-Ordinal Scale" 15 days Proportion of patients in categories 5, 6 or 7 of the 7-point ordinal scale at day 15 7- Ordinal scale:
1. Not hospitalized, no limitations on activities.
2. Not hospitalized, limitation on activities.
3. Hospitalized, not requiring supplemental oxygen.
4. Hospitalized, requiring supplemental oxygen.
5. Hospitalized, on non-invasive ventilation or high flow oxygen devices.
6. Hospitalized, on invasive mechanical ventilation or ECMO.
7. Death.
- Secondary Outcome Measures
Name Time Method Status at day 30 in the "7-point ordinal scale" 30 days Status at day 30 in the "7-point ordinal scale"
Time to category 5, 6 or 7 of the " 7-Ordinal scale" 29 days Time to change from baseline category to worsening into 5,6 or 7 categories of the "7-Ordinal scale"
Time to an improvement of one category from admission in the "7-Ordinal scale" 29 days Time to an improvement of one category from admission in the "7-Ordinal scale"
Time to first deterioration 60 days Time to first deterioration
Mean change in the ranking in the "7-Ordinal scale" from baseline to days 3,5,8,11,15,29 and 60 60 days Mean change in the ranking in the "7-Ordinal Scale" from baseline to days 3,5,8,11,15,29 and 60
Mean change in the ranking in the "11-Ordinal scale from baseline to days 3,5,8,11,15,29 and 60. 60 days Mean change in the ranking in the "11- Ordinal scale" from baseline to days 3,5,8,11,15,29 and 60.
Status at day 15 and 30 in the "11-Ordinal scale" 30 days Status at day 15 and 30 in the "11-Ordinal scale"
Status at day 15 and 30 in the "11-Ordinal scale"Mortality of any cause at 15 days 15 days Rate of mortality of any cause within first 15 days.
Mortality of any cause at 28 days (day 29) 28 days (day 29) Rate of mortality of any cause within first 28 days.
Mortality of any cause at 60 days 60 days Rate of mortality of any cause within first 60 days.
Oxygenation free days 29 days days free from oxygen supplementation
Ventilator free days 29 days days free from mechanical ventilation
Duration of hospitalization (days) 60 days days of hospitalization
Incidence of thrombotic arterial events 60 days incidence of thrombotic arterial events
Incidence of thrombotic venous events 60 days incidence of thrombotic venous events
Status at day 30 in the "11-Ordinal scale" 30 days Status at day 30 in the "11-Ordinal scale"
"11-Ordinal scale" :
0. Uninfected ; no viral RNA detected.
1. Asymptomatic; viral RNA detected, limitation on activities.
2. Symptomatic; independent
3. Symptomatic; assistance needed
4. Hospitalized, no oxygen therapy.
5. Hospitalized, oxygen by mask or nasal prongs
6. Oxygen by mask or nasal prongs
7. Intubation and mechanical ventilation, pO2/FiO2 ≥150 or SpO2/FiO2 ≥200
8. Mechanical ventilation pO2/FIO2 \<150 (SpO2/FiO2 \<200) or vasopressors
9. Mechanical ventilation pO2/FiO2 \<150 and vasopressors, dialysis, or ECMO
10. DeadInfusion-related adverse events 60 days Infusion-related adverse events Cumulative incidence of serious adverse events (SAEs) Cumulative incidence of Grade 3 and 4 adverse events (AEs).
Incidence of Treatment-Emergent Adverse Events 60 days cumulative incidence of Grade 3 and 4 adverse events (AEs) Cumulative incidence of serious adverse events (SAEs) Cumulative incidence of Grade 3 and 4 adverse events (AEs).
rate of rehospitalizations 60 days rehospitalizations
Antibodies levels in CP donors recovered from COVID-19 3 months Quantitative total antibodies and neutralizing antibody activity against SARSCoV-2 in the sera from donors and patients using viral pseudotypes
Viral load Days 1,3,5,8,11,15,29 and 60 Change in PCR for SARS-CoV-2 in blood on Days 3,5,8,11,15,29 and 60 (while hospitalized) until two of them are negative consecutively
Trial Locations
- Locations (29)
Hospital Universitario Mútua Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Clínica Universidad de Navarra (CUN). Sedes Pamplona y Madrid
🇪🇸Pamplona, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital General de Albacete
🇪🇸Albacete, Spain
Hospital General Universitario de Ciudad Real
🇪🇸Ciudad Real, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital Universitario de Asturias
🇪🇸Oviedo, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Spain
Complejo Hospitalario de Toledo
🇪🇸Toledo, Spain
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Spain
Hospital Clínico Universitario de Valladolid
🇪🇸Valladolid, Spain
Hospital Clínico Universitario Lozano Blesa
🇪🇸Zaragoza, Aragón, Spain
Hospital Doctor Negrín
🇪🇸Las Palmas, Spain
Hospital Universitario Arnau de Vilanova
🇪🇸Lleida, Spain
Complejo Asistencial Universitario de León
🇪🇸León, Spain
Hospital Universitario La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Donostia
🇪🇸Donostia, Spain
Hospital Doctor Josep Trueta
🇪🇸Girona, Spain
Hospital San Pedro
🇪🇸Logroño, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Hospital Sant Joan de Deu de Manresa. Fundación Althaia
🇪🇸Manresa, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain