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

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ClinicalTrials.gov Identifier: NCT04345523
Recruitment Status : Completed
First Posted : April 14, 2020
Last Update Posted : May 13, 2021
Sponsor:
Collaborator:
Instituto de Salud Carlos III
Information provided by (Responsible Party):
Cristina Avendaño Solá, Puerta de Hierro University Hospital

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
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.
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 : April 3, 2020
Actual Primary Completion Date : February 5, 2021
Actual Study Completion Date : April 5, 2021
Arms and Interventions
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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 Name: 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 Name: SOC


Outcome Measures
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Primary Outcome Measures :
  1. Category Changes in the "7-Ordinal Scale" [ Time Frame: 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 :
  1. Time to category 5, 6 or 7 of the " 7-Ordinal scale" [ Time Frame: 29 days ]
    Time to change from baseline category to worsening into 5,6 or 7 categories of the "7-Ordinal scale"

  2. Time to an improvement of one category from admission in the "7-Ordinal scale" [ Time Frame: 29 days ]
    Time to an improvement of one category from admission in the "7-Ordinal scale"

  3. Status at day 30 in the "11-Ordinal scale" [ Time Frame: 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. Dead

  4. Status at day 15 and 30 in the "11-Ordinal scale" [ Time Frame: 30 days ]

    Status at day 15 and 30 in the "11-Ordinal scale"

    Status at day 15 and 30 in the "11-Ordinal scale"


  5. Time to first deterioration [ Time Frame: 60 days ]
    Time to first deterioration

  6. Mean change in the ranking in the "7-Ordinal scale" from baseline to days 3,5,8,11,15,29 and 60 [ Time Frame: 60 days ]
    Mean change in the ranking in the "7-Ordinal Scale" from baseline to days 3,5,8,11,15,29 and 60

  7. Mean change in the ranking in the "11-Ordinal scale from baseline to days 3,5,8,11,15,29 and 60. [ Time Frame: 60 days ]
    Mean change in the ranking in the "11- Ordinal scale" from baseline to days 3,5,8,11,15,29 and 60.

  8. Mortality of any cause at 15 days [ Time Frame: 15 days ]
    Rate of mortality of any cause within first 15 days.

  9. Mortality of any cause at 28 days (day 29) [ Time Frame: 28 days (day 29) ]
    Rate of mortality of any cause within first 28 days.

  10. Mortality of any cause at 60 days [ Time Frame: 60 days ]
    Rate of mortality of any cause within first 60 days.

  11. Oxygenation free days [ Time Frame: 29 days ]
    days free from oxygen supplementation

  12. Ventilator free days [ Time Frame: 29 days ]
    days free from mechanical ventilation

  13. Duration of hospitalization (days) [ Time Frame: 60 days ]
    days of hospitalization

  14. Infusion-related adverse events [ Time Frame: 60 days ]
    Infusion-related adverse events Cumulative incidence of serious adverse events (SAEs) Cumulative incidence of Grade 3 and 4 adverse events (AEs).

  15. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 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).

  16. Antibodies levels in CP donors recovered from COVID-19 [ Time Frame: 3 months ]
    Quantitative total antibodies and neutralizing antibody activity against SARSCoV-2 in the sera from donors and patients using viral pseudotypes

  17. Viral load [ Time Frame: 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

  18. Viral load [ Time Frame: 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

  19. Incidence of thrombotic arterial events [ Time Frame: 60 days ]
    incidence of thrombotic arterial events

  20. Incidence of thrombotic venous events [ Time Frame: 60 days ]
    incidence of thrombotic venous events

  21. rate of rehospitalizations [ Time Frame: 60 days ]
    rehospitalizations


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04345523


Locations
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Sponsors and Collaborators
Cristina Avendaño Solá
Instituto de Salud Carlos III
Investigators
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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
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Avendaño-Solá C, Ramos-Martínez A, Muñez-Rubio E, Ruiz-Antorán B, Malo de Molina R, Torres F, Fernández-Cruz A, Calderón-Parra J, Payares-Herrera C, Díaz de Santiago A, Romera-Martínez I, Pintos I, Lora-Tamayo J, Mancheño-Losa M, Paciello ML, Martínez-González AL, Vidán-Estévez J, Nuñez-Orantos MJ, Saez-Serrano MI, Porras-Leal ML, Jarilla-Fernández MC, Villares P, de Oteyza JP, Ramos-Garrido A, Blanco L, Madrigal-Sánchez ME, Rubio-Batllés M, Velasco-Iglesias A, Paño-Pardo JR, Moreno-Chulilla JA, Muñiz-Díaz E, Casas-Flecha I, Pérez-Olmeda M, García-Pérez J, Alcamí J, Bueno JL, Duarte RF; ConPlas-19 Study Group. A multicenter randomized open-label clinical trial for convalescent plasma in patients hospitalized with COVID-19 pneumonia. J Clin Invest. 2021 Oct 15;131(20). pii: e152740. doi: 10.1172/JCI152740.

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Responsible Party: Cristina Avendaño Solá, MD, PhD, Puerta de Hierro University Hospital
ClinicalTrials.gov Identifier: NCT04345523    
Other Study ID Numbers: ConPlas-19
First Posted: April 14, 2020    Key Record Dates
Last Update Posted: May 13, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: PD that underlie the results reported in this article, after deidenficiation (text, tables, figures, and appendices) will be shared. The data will be available after main report is published.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research
Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cristina Avendaño Solá, Puerta de Hierro University Hospital:
COVID-19
Coronavirus
SARS-CoV-2
 Convalescent Plasma
SOC
CP
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases