Convalescent Plasma Therapy vs. SOC for the Treatment of COVID-19 in Hospitalized Patients

COVID-19 Clinical Trial

— ConPlas-19  

Official title:

Multi-center, Randomized Clinical Trial of Convalescent Plasma Therapy Versus Standard of Care for the Treatment of COVID-19 in Hospitalized Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04345523
• Other study ID #: ConPlas-19
• Status: Completed
• Phase: Phase 2
• Start date: April 3, 2020
• Est. completion date: April 5, 2021

Study information

• Verified date: May 2021
• Source: Puerta de Hierro University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: April 5, 2021
• Est. primary completion date: February 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Male or female adult patient =18 years of age at time of enrolment.

3. 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.

4. 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.

5. No more than 7 days between the onset of symptoms (fever or cough) and treatment administration day.

Exclusion Criteria:

1. Requiring mechanical ventilation (invasive or non-invasive) or high flow oxygen devices.

2. More than 7 days since symptoms (fever or cough).

3. Participation in any other clinical trial of an experimental treatment for COVID-19.

4. 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.

5. Any incompatibility or allergy to the administration of human plasma.

6. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30).

Related Conditions & MeSH terms

• COVID-19

Intervention

Other:
• Blood and derivatives.
Administration of fresh plasma from donor immunized against COVID-19

Drug:
• Standard of Care
Standard of care for the treatment of COVID-19 in hospitalized patients

Locations

Country	Name	City	State
Spain	Hospital General de Albacete	Albacete
Spain	Hospital del Mar	Barcelona
Spain	Hospital General Universitario de Ciudad Real	Ciudad Real
Spain	Hospital Universitario Donostia	Donostia
Spain	Hospital Doctor Josep Trueta	Girona
Spain	Hospital Doctor Negrín	Las Palmas
Spain	Complejo Asistencial Universitario de León	León
Spain	Hospital Universitario Arnau de Vilanova	Lleida
Spain	Hospital San Pedro	Logroño
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital Sant Joan de Deu de Manresa. Fundación Althaia	Manresa
Spain	Hospital Universitario de Asturias	Oviedo
Spain	Hospital Universitario Son Espases	Palma De Mallorca
Spain	Clínica Universidad de Navarra (CUN). Sedes Pamplona y Madrid	Pamplona
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Mútua Terrassa	Terrassa	Barcelona
Spain	Complejo Hospitalario de Toledo	Toledo
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza	Aragón
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Cristina Avendaño Solá	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Category Changes in the "7-Ordinal Scale"	Proportion of patients in categories 5, 6 or 7 of the 7-point ordinal scale at day 15 7- Ordinal scale: Not hospitalized, no limitations on activities.; Not hospitalized, limitation on activities.; Hospitalized, not requiring supplemental oxygen.; Hospitalized, requiring supplemental oxygen.; Hospitalized, on non-invasive ventilation or high flow oxygen devices.; Hospitalized, on invasive mechanical ventilation or ECMO.; Death.	15 days
Secondary	Time to category 5, 6 or 7 of the " 7-Ordinal scale"	Time to change from baseline category to worsening into 5,6 or 7 categories of the "7-Ordinal scale"	29 days
Secondary	Time to an improvement of one category from admission in the "7-Ordinal scale"	Time to an improvement of one category from admission in the "7-Ordinal scale"	29 days
Secondary	Status at day 30 in the "11-Ordinal scale"	Status at day 30 in the "11-Ordinal scale"; "11-Ordinal scale" : 0. Uninfected ; no viral RNA detected.; Asymptomatic; viral RNA detected, limitation on activities.; Symptomatic; independent; Symptomatic; assistance needed; Hospitalized, no oxygen therapy.; Hospitalized, oxygen by mask or nasal prongs; Oxygen by mask or nasal prongs; Intubation and mechanical ventilation, pO2/FiO2 =150 or SpO2/FiO2 =200; Mechanical ventilation pO2/FIO2 <150 (SpO2/FiO2 <200) or vasopressors; Mechanical ventilation pO2/FiO2 <150 and vasopressors, dialysis, or ECMO; Dead	30 days
Secondary	Status at day 15 and 30 in the "11-Ordinal scale"	Status at day 15 and 30 in the "11-Ordinal scale"; Status at day 15 and 30 in the "11-Ordinal scale"	30 days
Secondary	Time to first deterioration	Time to first deterioration	60 days
Secondary	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 "7-Ordinal Scale" from baseline to days 3,5,8,11,15,29 and 60	60 days
Secondary	Mean change in the ranking in the "11-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
Secondary	Mortality of any cause at 15 days	Rate of mortality of any cause within first 15 days.	15 days
Secondary	Mortality of any cause at 28 days (day 29)	Rate of mortality of any cause within first 28 days.	28 days (day 29)
Secondary	Mortality of any cause at 60 days	Rate of mortality of any cause within first 60 days.	60 days
Secondary	Oxygenation free days	days free from oxygen supplementation	29 days
Secondary	Ventilator free days	days free from mechanical ventilation	29 days
Secondary	Duration of hospitalization (days)	days of hospitalization	60 days
Secondary	Infusion-related adverse events	Infusion-related adverse events Cumulative incidence of serious adverse events (SAEs) Cumulative incidence of Grade 3 and 4 adverse events (AEs).	60 days
Secondary	Incidence of Treatment-Emergent Adverse Events	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).	60 days
Secondary	Antibodies levels in CP donors recovered from COVID-19	Quantitative total antibodies and neutralizing antibody activity against SARSCoV-2 in the sera from donors and patients using viral pseudotypes	3 months
Secondary	Viral load	Change in PCR for SARS-CoV-2 in naso/oropharyngeal swabs at baseline and at discharge	Days 1,3,5,8,11,15, 29 and 60
Secondary	Viral load	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	Days 1,3,5,8,11,15,29 and 60
Secondary	Incidence of thrombotic arterial events	incidence of thrombotic arterial events	60 days
Secondary	Incidence of thrombotic venous events	incidence of thrombotic venous events	60 days
Secondary	rate of rehospitalizations	rehospitalizations	60 days