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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

Tracking Information
First Submitted Date  ICMJE April 2, 2020
First Posted Date  ICMJE April 14, 2020
Last Update Posted Date May 13, 2021
Actual Study Start Date  ICMJE April 3, 2020
Actual Primary Completion Date February 5, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 10, 2020)
Category Changes in Ordinal Scale [ Time Frame: 15 days ]
Proportion of patients in categories 5, 6 or 7 of the 7-point ordinal scale at day 15 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 or oxygen mask with reservoir bag.
  6. Hospitalized, on invasive mechanical ventilation or ECMO.
  7. Death.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2021)
  • 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"
  • 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"
  • 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
  • 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"
  • Time to first deterioration [ Time Frame: 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 [ 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
  • 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.
  • Mortality of any cause at 15 days [ Time Frame: 15 days ]
    Rate of mortality of any cause within first 15 days.
  • 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.
  • Mortality of any cause at 60 days [ Time Frame: 60 days ]
    Rate of mortality of any cause within first 60 days.
  • Oxygenation free days [ Time Frame: 29 days ]
    days free from oxygen supplementation
  • Ventilator free days [ Time Frame: 29 days ]
    days free from mechanical ventilation
  • Duration of hospitalization (days) [ Time Frame: 60 days ]
    days of hospitalization
  • 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).
  • 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).
  • 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
  • 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
  • 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
  • Incidence of thrombotic arterial events [ Time Frame: 60 days ]
    incidence of thrombotic arterial events
  • Incidence of thrombotic venous events [ Time Frame: 60 days ]
    incidence of thrombotic venous events
  • rate of rehospitalizations [ Time Frame: 60 days ]
    rehospitalizations
Original Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2020)
  • Time to category 5, 6 or 7 of the ordinal scale [ Time Frame: 29 days ]
    Time to change from baseline category to worsening into 5,6 or 7 categories of the ordinal scale
  • Mortality of any cause at 14 days [ Time Frame: 15 days ]
    Mortality
  • Mortality of any cause at 28 days [ Time Frame: 29 days ]
    Mortality
  • Oxygenation free days [ Time Frame: 29 days ]
    days free from oxygen supplementation
  • Ventilator free days [ Time Frame: 29 days ]
    days free from mechanical ventilation
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: 29 days ]
    Infusion-related adverse events 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 [ Time Frame: 3 months ]
    Quantitative total antibodies and neutralizing antibody activity against SARSCoV-2 in the sera from donors and patients using viral pseudotypes
  • Viral load [ Time Frame: Days 1,3,5,8,11 and 29 ]
    Change in PCR for SARS-CoV-2 in naso/oropharyngeal swabs and blood at baseline and on days 3, 5, 8, 11 (while hospitalized); and days 15 and 29 (if able to return to clinic or still hospitalized).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: April 10, 2020)
Change in biological parameters [ Time Frame: Days 1,3,5,8,11 and 29 ]
Serum levels of CRP, lymphocyte count, LDH, D Dimer,IL-6, coagulation tests at baseline and days 3, 5, 8, 11, 15 and 29.
 
Descriptive Information
Brief Title  ICMJE Convalescent Plasma Therapy vs. SOC for the Treatment of COVID-19 in Hospitalized Patients
Official Title  ICMJE Multi-center, Randomized Clinical Trial of Convalescent Plasma Therapy Versus Standard of Care for the Treatment of COVID-19 in Hospitalized Patients
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Other: Blood and derivatives.
    Administration of fresh plasma from donor immunized against COVID-19
    Other Name: Convalescent Plasma from patients recovered from COVID-19
  • Drug: Standard of Care
    Standard of care for the treatment of COVID-19 in hospitalized patients
    Other Name: SOC
Study Arms  ICMJE
  • Experimental: Treatment Arm
    Pathogen-reduced CP from patients recovered from COVID-19, whom, for the purpose of this trial, are herein designated as donors.
    Intervention: Other: Blood and derivatives.
  • Active Comparator: Control Arm
    Standard of Care (SOC) for COVID-19
    Intervention: Drug: Standard of Care
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 12, 2021)
350
Original Estimated Enrollment  ICMJE
 (submitted: April 10, 2020)
278
Actual Study Completion Date  ICMJE April 5, 2021
Actual Primary Completion Date February 5, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04345523
Other Study ID Numbers  ICMJE ConPlas-19
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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.
Responsible Party Cristina Avendaño Solá, Puerta de Hierro University Hospital
Study Sponsor  ICMJE Cristina Avendaño Solá
Collaborators  ICMJE Instituto de Salud Carlos III
Investigators  ICMJE
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
PRS Account Puerta de Hierro University Hospital
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP