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A Clinical Trial of Convalescent Plasma Compared to Best Supportive Care for Treatment of Patients With Severe COVID-19 (CAPSID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04433910
Recruitment Status : Completed
First Posted : June 16, 2020
Last Update Posted : March 17, 2021
Sponsor:
Information provided by (Responsible Party):
Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen

Tracking Information
First Submitted Date  ICMJE May 6, 2020
First Posted Date  ICMJE June 16, 2020
Last Update Posted Date March 17, 2021
Actual Study Start Date  ICMJE August 30, 2020
Actual Primary Completion Date January 21, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2020)
Composite endpoint of survival and no longer fulfilling criteria of severe COVID-19. [ Time Frame: Day 21 ]
Dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19. All criteria must be met in order to fulfil the primary endpoint.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2020)
  • Time to clinical improvement [ Time Frame: day 0 to discharge within a 60 day period ]
    Time to clinical improvement (defined as time from randomization to an improvement of two points on the WHO R&D Blueprint seven-category ordinal scale for clinical improvement)(Key secondary endpoint)
  • Frequency and severity of adverse events by CTCAE v5.0, (Key secondary endpoint) [ Time Frame: day 0 to discharge within a 60 day period ]
  • Case fatality rate [ Time Frame: on day 21, 35 and 60 ]
  • Length of hospital stay Length of hospital stay (if applicable) [ Time Frame: day 0 to 60 ]
  • Length of stay in ICU [ Time Frame: day 0 to 60 ]
  • Duration of ventilation support / ECMO [ Time Frame: day 0 to 60 ]
  • Time until negative SARS-CoV-2 PCR (nasopharyngeal sample) [ Time Frame: day 0 to 60 ]
  • Predictive value of comorbidities [ Time Frame: day 0 to 60 ]
    Comorbidities will be assessed and correlated to clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days)
  • Predictive value of coagulation markers [ Time Frame: day 0 to 60 ]
    Correlation of coagulation markers (D-Dimers, prothrombin time, Partial Thromboplastin Time, ATIII, Fibrinogen) with clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days)
  • Predictive value of inflamation [ Time Frame: day 0 to 60 ]
    Corelation of Inflammation (laboratory testing: CRP, IL-6, Ferritin, Blood cell Count) with clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days)
  • Percentage of former COVID-19 patients willing to donate qualifying for plasma donation. [ Time Frame: through study completion, an average of 8 months ]
  • Amount of Plasma Units that could be collected for the clinical trial [ Time Frame: through study completion, an average of 8 months ]
  • Titer of anti-SARS-CoV-2 in transfused plasma units [ Time Frame: any plasmaphereseis, through study completion, an average of 8 months ]
  • Impact of donor characteristics on anti-SARS-CoV-2 humoral response [ Time Frame: up to 60 days ]
    Anti-SARS-CoV-2-antibody titers will be correlated with age; gender; severity of COVID-19; interval between resolution of symptoms and plasmapheresis of plasma donors
  • Course of anti-SARS-CoV-2 titer in both patient groups at different time points related to transfusion of convalescent plasma [ Time Frame: up to 60 days ]
  • Correlation of anti-SARS-CoV-2 titer in transfused plasma units and primary and key secondary outcomes. [ Time Frame: day 0 to 60 ]
    Correlation of antibody titers with: 1. "Survival and no longer fulfilling criteria of severe COVID-19"; 2. Change in WHO ordinal scale; 3. Time to clinical improvement; 4. Length of hospital stay; 5. Length of ICU stay; 6. Length of mechanical Ventilation or ECMO support.
  • Effect of timing of plasma transfusions [ Time Frame: day 0 to 60 ]
    Effect of timing of plasma transfusions on outcome: comparison of early treatment, i.e. day 1, 3 and 5 in convalescent plasma group vs. delayed treatment, i.e. day 15, 17, 19 in patients crossing over from control group due to progressive disease on day-14 assessment.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial of Convalescent Plasma Compared to Best Supportive Care for Treatment of Patients With Severe COVID-19
Official Title  ICMJE A Randomized, Prospective, Open Label Clinical Trial on the Use of Convalescent Plasma Compared to Best Supportive Care in Patients With Severe COVID-19
Brief Summary

This is a randomized, prospective, multicenter, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.

The aim of the study is to explore the therapeutic effect of convalescent plasma transfusions on the survival and course of disease of patients with severe COVID-19. Convalescent plasma will be collected from recovered COVID-19 patients.

Patients with severe COVID-19 will be randomly assigned to two groups. Patients in the treatment group will receive covalescent plasma (250 - 325 ml) on days 1, 3 and 5. Patients in the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline, patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19.

Fifty-three patients will be included in each group. Data of each patient will be collected until discharge but nor longer than day 60.

Detailed Description

This is a randomized, prospective, multicentre, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.

The primary Endpoint is a dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19 within 21 days after randomization. All criteria must be met in order to fulfil the primary endpoint.

Key secondary endpoints are time to clinical improvement (defined as time from randomization to an improvement of two points on the WHO R&D Blueprint seven-category ordinal scale for clinical improvement), the frequency and severity of adverse events and the case fatality rate on day 21, 35 and 60. Further secondary endpoints refer to the course of anti-SARS-CoV-2 antibodies in plasma donors and treated patients and the impact of donor criteria on the effectiveness of plasma units.

Patients with severe COVID-19 defined by a respiratory rate ≥ 30 breaths / minute under ambient air or the requirement of any type of ventilation support or the need for ICU treatment can be included in the trial. It is planned to enrol 106 patients. Patients will be stratified according to ventilation support and/or extracorporeal oxygenation and/or ICU treatment and will be equally asigned to two groups. The treatment group receives convalescent plasma (250 - 325 ml) on day 1, 3 and 5 and the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline (i.e. day 0), patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19. A patient switching from the control group to convalescent plasma group because of progressive COVID-19 on day 14 will be considered as failure of the primary endpoint at final evaluation of the primary endpoint on day 21.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE Drug: Convalesscent Plasma
Transfusion
Study Arms  ICMJE
  • Experimental: Convalescent plasma
    Convalescent plasma transfusion on day 1, 3 and 5.
    Intervention: Drug: Convalesscent Plasma
  • No Intervention: Best supportive care
    Best supportive care, cross over for patients with progressive disease on day 14 with convalescent plasma transfusion on day 15, 17 and 19.
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: June 15, 2020)
106
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 22, 2021
Actual Primary Completion Date January 21, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patients with SARS-CoV-2 infection and

  1. age ≥ 18 years and ≤ 75 years
  2. SARS-CoV-2 infection confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap)
  3. severe disease defined by at least one of the following:

    1. respiratory rate ≥ 30 breaths / minute under ambient air
    2. requirement of any type of ventilation support
    3. needs ICU treatment
  4. Written informed consent by patient or legally authorized representative

Exclusion Criteria:

  1. Accompanying diseases other than COVID-19 with an expected survival time of less than 12 months.
  2. Previous treatment with any SARS-CoV-2-convalescent plasma
  3. In the opinion of the clinical team, progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatment
  4. Interval > 72 hours since start of ventilation support
  5. Not considered eligible for extracorporeal oxygenation support (even in case of severe ARDS according to Berlin classification with Horovitz-Index < 100 mg Hg)
  6. Chronic obstructive lung disease (COPD), stage 4
  7. Lung fibrosis with UIP pattern in CT und severe emphysema
  8. Chronic heart failure NYHA >= 3 and/or pre-existing reduction of left ventricular ejection fraction to ≤ 30%
  9. Shock of any type requiring ≥ 0.5 µg/kg/min noradrenaline (or equivalent) or requiring more than two types of vasopressor medication for more than 8 hours
  10. Liver cirrhosis Child C
  11. Liver failure: Bilirubin > 5xULN and elevation of ALT /AST (at least one >10xULN).
  12. Any history of adverse reactions to plasma proteins
  13. Known deficiency of immunoglobulin A
  14. Pregnancy
  15. Breastfeeding women
  16. Volume overload until sufficiently treated
  17. Participation in another clinical trial with an investigational medicinal product
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (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 Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04433910
Other Study ID Numbers  ICMJE CAPSID2020-DRK-BSD
2020-001310-38 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
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: No
Current Responsible Party Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hubert Schrezenmeier, Prof.Dr. IKT Ulm
Study Director: Erhard Seifried, Prof.Dr.Dr. German Red Cross Blood Service
PRS Account Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen
Verification Date March 2021

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