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

Phase 2

Completed

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

• Registration Number: NCT04558476
• Lead Sponsor: University of Liege

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 Timeline

• Study Start: 2020-09-11
• Study First Submitted: 2020-09-14
• Study First Submitted QC: 2020-09-21
• Study First Posted: 2020-09-22
• Primary Completion: 2022-04-09
• Study Completion: 2023-03-09
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-25
• Last Update Posted: 2024-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 475

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	Standard of Care	Standard of care according the last gold standards
Convalescent Plasma	Convalescent Plasma	2 units of plasma ( 400-500ml) from 2 different donnors duration of treatment =2 h

Primary Outcome Measures

Name	Time	Method
Vital status	at day 28	dead or alive

Secondary Outcome Measures

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

Trial Locations

Locations (17)

UZ Antwerpen; 🇧🇪 Antwerp, Belgium

CHR Citadelle; 🇧🇪 Liège, Belgium

Clinique Saint Pierre Ottignies; 🇧🇪 Ottignies, Brabant Wallon, Belgium

Imelda ZH Bonheiden; 🇧🇪 Bonheiden, Belgium

OLVZ Aalst; 🇧🇪 Aalst, Belgium

Erasme; 🇧🇪 Brussels, Belgium

CHU Saint Pierre; 🇧🇪 Brussels, Belgium

CHU Charleroi Marie Curie; 🇧🇪 Charleroi, Belgium

UZ Brussel; 🇧🇪 Brussel, Belgium

AZ Sint Blasius; 🇧🇪 Dendermonde, Belgium

UZ Gent; 🇧🇪 Gent, Belgium

AZ Groeningen Kortrijck; 🇧🇪 Kortrijk, Belgium

CHU Liège; 🇧🇪 Liège, Belgium

UC Louvain; 🇧🇪 Louvain, Belgium

AZ Delta; 🇧🇪 Roeselare, Belgium

CHU UCL Namur-Godinne; 🇧🇪 Yvoir, Belgium

Centre Hospitalier Wallonie Picarde; 🇧🇪 Tournai, Hainaut, Belgium