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

Sponsor

Cristina Avendaño Solá (Other)

Overall Status

Completed

CT.gov ID

NCT04345523

Collaborator

Instituto de Salud Carlos III (Other)

350

Enrollment

Locations

Arms

12.1

Actual Duration (Months)

12.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Other: Blood and derivatives. Drug: Standard of Care	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

350 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

1:1 ratio for CP: Control arm. Also, approximately 140-200 CP donors.1:1 ratio for CP: Control arm. Also, approximately 140-200 CP donors.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 3, 2020

Actual Primary Completion Date :

Feb 5, 2021

Actual Study Completion Date :

Apr 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Pathogen-reduced CP from patients recovered from COVID-19, whom, for the purpose of this trial, are herein designated as donors.	Other: Blood and derivatives. Administration of fresh plasma from donor immunized against COVID-19 Other Names: Convalescent Plasma from patients recovered from COVID-19
Active Comparator: Control Arm Standard of Care (SOC) for COVID-19	Drug: Standard of Care Standard of care for the treatment of COVID-19 in hospitalized patients Other Names: SOC

Arm

Intervention/Treatment

Experimental: Treatment Arm

Pathogen-reduced CP from patients recovered from COVID-19, whom, for the purpose of this trial, are herein designated as donors.

Other: Blood and derivatives.

Administration of fresh plasma from donor immunized against COVID-19

Other Names:

Convalescent Plasma from patients recovered from COVID-19

Active Comparator: Control Arm

Standard of Care (SOC) for COVID-19

Drug: Standard of Care

Standard of care for the treatment of COVID-19 in hospitalized patients

Other Names:

SOC

Outcome Measures

Primary Outcome Measures

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: 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.

Secondary Outcome Measures

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"
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. 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
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"
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.
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
Infusion-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).
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 naso/oropharyngeal swabs at baseline and at discharge
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
Incidence of thrombotic arterial events [60 days]
incidence of thrombotic arterial events
Incidence of thrombotic venous events [60 days]
incidence of thrombotic venous events
rate of rehospitalizations [60 days]
rehospitalizations

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clínico Universitario Lozano Blesa	Zaragoza	Aragón	Spain	50009
2	Hospital Universitario Mútua Terrassa	Terrassa	Barcelona	Spain	08221
3	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
4	Hospital General de Albacete	Albacete		Spain	02006
5	Hospital del Mar	Barcelona		Spain	08003
6	Hospital General Universitario de Ciudad Real	Ciudad Real		Spain	13005
7	Hospital Universitario Donostia	Donostia		Spain	20014
8	Hospital Doctor Josep Trueta	Girona		Spain	17007
9	Hospital Doctor Negrín	Las Palmas		Spain	35010
10	Complejo Asistencial Universitario de León	León		Spain	24071
11	Hospital Universitario Arnau de Vilanova	Lleida		Spain	25198
12	Hospital San Pedro	Logroño		Spain	26006
13	Hospital Universitario La Princesa	Madrid		Spain	28006
14	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28009
15	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
16	Hospital Clínico San Carlos	Madrid		Spain	28040
17	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
18	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
19	Hospital Sant Joan de Deu de Manresa. Fundación Althaia	Manresa		Spain	08243
20	Hospital Universitario de Asturias	Oviedo		Spain	33011
21	Hospital Universitario Son Espases	Palma De Mallorca		Spain	07120
22	Clínica Universidad de Navarra (CUN). Sedes Pamplona y Madrid	Pamplona		Spain	31008
23	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
24	Hospital Universitario de Salamanca	Salamanca		Spain
25	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
26	Complejo Hospitalario de Toledo	Toledo		Spain	45007
27	Hospital General Universitario de Valencia	Valencia		Spain	46014
28	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47003
29	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009

Sponsors and Collaborators

Cristina Avendaño Solá
Instituto de Salud Carlos III

Investigators

Study Chair: Cristina Avendaño Solá, MD, PhD, Hospital Universitario Puerta de Hierro Majadahonda
Study Chair: Rafael Duarte Palomino, MD, PhD, Hospital Universitario Puerta de Hierro Majadahonda
Principal Investigator: Antonio Ramos, MD, PhD, Hospital Universitario Puerta de Hierro Majadahonda
Principal Investigator: José Luis Bueno, MD, Hospital Universitario Puerta de Hierro Majadahonda
Principal Investigator: Inmaculada Casas Flecha, PharmD, PhD, Centro Nacional de Microbiología, Instituto de Salud Carlos III