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

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Respiratory Failure; Corona Virus Infection; Mechanical Ventilation Complication; SARS (Severe Acute Respiratory Syndrome)
• Intervention / Treatment: Biological: Convalescent Plasma; Other: Standard of Care

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: Interventional
• Enrollment (Actual): 475
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • OLVZ Aalst
  • Antwerp, Belgium, 2650
    • UZ Antwerpen
  • Bonheiden, Belgium, 2820
    • Imelda ZH Bonheiden
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Brussels, Belgium, 1000
    • CHU Saint Pierre
  • Brussels, Belgium, 1070
    • Erasme
  • Charleroi, Belgium, 6042
    • CHU Charleroi Marie Curie
  • Dendermonde, Belgium, 9200
    • AZ Sint Blasius
  • Gent, Belgium, 9000
    • Uz Gent
  • Kortrijk, Belgium, 8500
    • AZ Groeningen Kortrijck
  • Liège, Belgium, 4000
    • Chu Liege
  • Liège, Belgium, 4000
    • CHR Citadelle
  • Louvain, Belgium, 1200
    • UC Louvain
  • Roeselare, Belgium, 8800
    • AZ Delta
  • Yvoir, Belgium, 5530
    • CHU UCL Namur-Godinne
  • Brabant Wallon
    • Ottignies, Brabant Wallon, Belgium, 1340
      • Clinique Saint Pierre Ottignies
  • Hainaut
    • Tournai, Hainaut, Belgium, 7500
      • Centre Hospitalier Wallonie Picarde

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Convalescent Plasma; 2 units of plasma ( 400-500ml) from 2 different donnors duration of treatment =2 h	Biological: Convalescent Plasma; 2 units of convalescent plasma
Other: Standard of care; Standard of care according the last gold standards	Other: Standard of Care; Gold Standards

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital status	dead or alive	at day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
day 90 mortality	dead or alive	at day 90
number of ventilator-free days at day 28	to assess the ventilator free days	at day 28
number of renal replacement therapy free days at day 28	to assess the number of renal replacement therapy free days	at day 28
number of vasopressors free-days at day 28	to assess the number of vasopressors free-days	at day 28
use of ECMO before day 28	to assess if ECMO was required	till day 28
value of the SOFA score at days 7, 14 and 28	to assess the value of SOFA score	Day 1, 7, 14, 28
changes in SOFA scores (delta SOFA) over 7, 14 and 28 days	to assess the changes in SOFA scores (delta SOFA)	Day 7, 14 and 28 days
assessment of the SARS-CoV-2 viral load	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	Days 7, 14 and 28
blood C reactive protein (CRP) concentration	to assess the concentrations of C reactive protein (CRP)	Days 7, 14 and 28
ferritin concentration	to assess the concentration of ferritin	Days 7, 14 and 28
lymphocyte count	to assess the count of lymphocyte	Days 7, 14 and 28
length of stay in the acute care hospital	to assess the lenght of stay in the acute care	through study completion, 1 year
location of the patient	to assess the location of the patient : acute care hospital, post acute care hospital, long-term residency, home	Day 90
Katz Index of independence in Activity Day Living functional score	to assess the Activity Day Living functional Min value: 0 = Low (patient very dependent) Max value: 6 = High (patient independent)	Day 90 and 365
Hospital Anxiety and Depression Scale (HADS)	to evaluate the anxiety-depression For each item 0-7 : Normal 8-10 : Bordeline abnormal (borderline case) 11-21 : Abnormal case	Day 90 and 365
Quality of life scale EQ-5D-5L	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'.	Day 90 and 365
Transfusion related adverse events	to assess the transfusion related adverse events	till 28 days
Determine the type of concommittent inflammatory response	assess clusters based on the profile of cytokines, chemokines and cell adhesion markers	till 28 days

Collaborators and Investigators

• Sponsor: University of Liege
• Collaborators: KCE Belgian Healthcare Knowledge Centre

Publications and helpful links

General 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. doi: 10.1186/s12890-021-01574-8.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2020
• Primary Completion (Actual): April 9, 2022
• Study Completion (Actual): March 9, 2023

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): October 29, 2024
• Last Update Submitted That Met QC Criteria: October 25, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Covid 19; Convalescent plasmatherapy; SARS Cov-2 pneumonia
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Respiratory Insufficiency; Coronavirus Infections; Severe Acute Respiratory Syndrome
• Other Study ID Numbers: 2020-003102-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No