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Efficacy of CONvalescent Plasma in Patients With COVID-19 Treated With Mechanical Ventilation (CONFIDENT)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04558476
Recruitment Status : Recruiting
First Posted : September 22, 2020
Last Update Posted : May 28, 2021
Sponsor:
Collaborator:
KCE Belgian Healthcare Knowledge Centre
Information provided by (Responsible Party):
Misset Benoit, University of Liege

Tracking Information
First Submitted Date  ICMJE September 14, 2020
First Posted Date  ICMJE September 22, 2020
Last Update Posted Date May 28, 2021
Actual Study Start Date  ICMJE September 1, 2020
Estimated Primary Completion Date September 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2020)
Vital status [ Time Frame: at day 28 ]
dead or alive
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2020)
  • day 90 mortality [ Time Frame: at day 90 ]
    dead or alive
  • number of ventilator-free days at day 28 [ Time Frame: at day 28 ]
    to assess the ventilator free days
  • number of renal replacement therapy free days at day 28 [ Time Frame: at day 28 ]
    to assess the number of renal replacement therapy free days
  • number of vasopressors free-days at day 28 [ Time Frame: at day 28 ]
    to assess the number of vasopressors free-days
  • use of ECMO before day 28 [ Time Frame: till day 28 ]
    to assess if ECMO was required
  • value of the SOFA score at days 7, 14 and 28 [ Time Frame: Day 1, 7, 14, 28 ]
    to assess the value of SOFA score
  • changes in SOFA scores (delta SOFA) over 7, 14 and 28 days [ Time Frame: Day 7, 14 and 28 days ]
    to assess the changes in SOFA scores (delta SOFA)
  • assessment of the SARS-CoV-2 viral load [ Time Frame: Days 7, 14 and 28 ]
    assessment of the SARS-CoV-2 viral load, expressed as cycle threshold, [2] in the tracheal aspirates (for intubated patients) or nasopharyngeal swabs (for extubated patients) at days 7, 14 and 28
  • blood C reactive protein (CRP) concentration [ Time Frame: Days 7, 14 and 28 ]
    to assess the concentrations of C reactive protein (CRP)
  • ferritin concentration [ Time Frame: Days 7, 14 and 28 ]
    to assess the concentration of ferritin
  • lymphocyte count [ Time Frame: Days 7, 14 and 28 ]
    to assess the count of lymphocyte
  • length of stay in the acute care hospital [ Time Frame: through study completion, 1 year ]
    to assess the lenght of stay in the acute care
  • location of the patient [ Time Frame: Day 90 ]
    to assess the location of the patient : acute care hospital, post acute care hospital, long-term residency, home
  • Katz Index of independence in Activity Day Living functional score [ Time Frame: Day 90 and 365 ]
    to assess the Activity Day Living functional Min value: 0 = Low (patient very dependent) Max value: 6 = High (patient independent)
  • Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Day 90 and 365 ]
    to evaluate the anxiety-depression For each item 0-7 : Normal 8-10 : Bordeline abnormal (borderline case) 11-21 : Abnormal case
  • Quality of life scale EQ-5D-5L [ Time Frame: Day 90 and 365 ]
    The EQ-5D-5L is composed of - the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Each level corresponds to 1-digit number expressing the level selected for that dimension. The EQ VAS corresponds to a 20 cm vertical, visual analogue scale raging from 'the best health you can imagine' to 'the worst health you can imagine'.
  • Transfusion related adverse events [ Time Frame: till 28 days ]
    to assess the transfusion related adverse events
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 Efficacy of CONvalescent Plasma in Patients With COVID-19 Treated With Mechanical Ventilation
Official Title  ICMJE A Multicenter Randomized Trial to Assess the Efficacy of CONvalescent Plasma Therapy in Patients With Invasive COVID-19 and Acute Respiratory Failure Treated With Mechanical Ventilation: the CONFIDENT Trial
Brief Summary The principal objective of the CONFIDENT trial is to assess the efficacy of two units (400-500 mL in total) of convalescent plasma, as compared to Standard of Care (SoC), to reduce day-28 mortality in patients with SARS-CoV-2 pneumonia who require mechanical ventilation.
Detailed Description

Design : multicenter randomized openlabel, phase II trial.

Number of patients to include : 500 (250 with plasma, 250 without plasma).

The principal objective is to assess the efficacy of the treatment to reduce day-28 mortality in patients with SARS-CoV-2 pneumonia who require mechanical ventilation.

Hypothesis: Passive immunization with plasma collected from patients having contracted COVID-19 and developed specific antibodies may alleviate symptoms and viral load of SARS-CoV-2 and reduce mortality.

The patients will receive currently accepted standard of care for both COVID-19 and usual organ dysfunctions observed in such cases. half the patients will be administered either Convalescent plasma, depending on the randomization process. All patients will be followed-up for one year after inclusion. The study will be considered either positive or negative, based on the principal objective. This means that the product convalescent plasme will be considered effective if mortality at day 28 is lower is patients treated with convalescent plasma than without it. The follow-up will allow to assess a series of secondary objectives, addressing the evolution of organ failures, viral infection, inflammatory response and long-term physical of psychological impact of COVID-19. Interim analyses will be performed every 100 patients included in order to stop the trial if an exceptionally good or bad result is observed, to prevent using or not using the product appropriately in further patients. These analyses will be supervised by an independent committee.

The choice to include only those patients under mechanical ventilation for severe respiratory failure makes this study different from other trials testing convalescent plasma, as most trial include less severe patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Covid19
  • Mechanical Ventilation Complication
  • Corona Virus Infection
  • Respiratory Failure
  • SARS (Severe Acute Respiratory Syndrome)
Intervention  ICMJE
  • Biological: Convalescent Plasma
    2 units of convalescent plasma
  • Other: Standard of Care
    Gold Standards
Study Arms  ICMJE
  • Experimental: Convalescent Plasma
    2 units of plasma ( 400-500ml) from 2 different donnors duration of treatment =2 h
    Intervention: Biological: Convalescent Plasma
  • Standard of care
    Standard of care according the last gold standards
    Intervention: Other: Standard of Care
Publications * Misset B, Hoste E, Donneau AF, Grimaldi D, Meyfroidt G, Moutschen M, Compernolle V, Gothot A, Desmecht D, Garigliany M, Najdovski T, Laterre PF. A multicenter randomized trial to assess the efficacy of CONvalescent plasma therapy in patients with Invasive COVID-19 and acute respiratory failure treated with mechanical ventilation: the CONFIDENT trial protocol. BMC Pulm Med. 2020 Dec 7;20(1):317. doi: 10.1186/s12890-020-01361-x. Erratum in: BMC Pulm Med. 2021 Jul 26;21(1):248.

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 21, 2020)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2022
Estimated Primary Completion Date September 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • age at least 18 years
  • hospitalization in an intensive care unit participating to the study
  • medical diagnosis with SARS-CoV-2 pneumonia as defined by both:

    • extended interstitial pneumonia on CT scan or a chest X-ray, consistent with viral pneumonia, within 10 days prior to inclusion
    • Positive result of SARS-CoV-2 PCR test, or any emerging and validated diagnostic laboratory test for COVID-19, within 15 days prior to inclusion
  • under mechanical ventilation administered through an endotracheal tube, for less than 5 days
  • prior Clinical Frailty Scale < 6.
  • written consent of the patient, or - if impossible - of a relative acting as the legal representative, or - if impossible - of a physician from a non-participating department of the same hospital acting as an impartial witness .

Exclusion Criteria:

  • Pregnancy
  • Prior episode of transfusion-related side effect
  • Medical decision to limit therapy
  • Current participation in another trial testing a COVID-19 therapy
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: Benoit Misset, MD,PhD 003243667495 benoit.misset@chuliege.be
Contact: Axelle Bertand 003242843975 Axelle.Bertrand@chuliege.be
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04558476
Other Study ID Numbers  ICMJE 2020-003102-31
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 Not Provided
Responsible Party Misset Benoit, University of Liege
Study Sponsor  ICMJE University of Liege
Collaborators  ICMJE KCE Belgian Healthcare Knowledge Centre
Investigators  ICMJE Not Provided
PRS Account University of Liege
Verification Date May 2021

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