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

Sponsor

University of Liege (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04558476

Collaborator

KCE Belgian Healthcare Knowledge Centre (Other)

475

Enrollment

Locations

Arms

30.6

Anticipated Duration (Months)

27.9

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 Mechanical Ventilation Complication Corona Virus Infection Respiratory Failure SARS (Severe Acute Respiratory Syndrome)	Biological: Convalescent Plasma Other: Standard of Care	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

475 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 11, 2020

Actual Primary Completion Date :

Apr 9, 2022

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Vital status [at day 28]
dead or alive

Secondary Outcome Measures

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
number of vasopressors free-days at day 28 [at day 28]
to assess the number of vasopressors free-days
use of ECMO before day 28 [till day 28]
to assess if ECMO was required
value of the SOFA score at days 7, 14 and 28 [Day 1, 7, 14, 28]
to assess the value of SOFA score
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)
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
blood C reactive protein (CRP) concentration [Days 7, 14 and 28]
to assess the concentrations of C reactive protein (CRP)
ferritin concentration [Days 7, 14 and 28]
to assess the concentration of ferritin
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
location of the patient [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 [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) [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'.
Transfusion related adverse events [till 28 days]
to assess the transfusion related adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinique Saint Pierre Ottignies	Ottignies	Brabant Wallon	Belgium	1340
2	Centre Hospitalier Wallonie Picarde	Tournai	Hainaut	Belgium	7500
3	OLVZ Aalst	Aalst		Belgium	9300
4	UZ Antwerpen	Antwerp		Belgium	2650
5	Imelda ZH Bonheiden	Bonheiden		Belgium	2820
6	CHU Saint Pierre	Brussels		Belgium	1000
7	Erasme	Brussels		Belgium	1070
8	UZ Brussel	Brussel		Belgium	1090
9	CHU Charleroi Marie Curie	Charleroi		Belgium	6042
10	AZ Sint Blasius	Dendermonde		Belgium	9200
11	UZ Gent	Gent		Belgium	9000
12	AZ Groeningen Kortrijck	Kortrijk		Belgium	8500
13	CHR Citadelle	Liège		Belgium	4000
14	CHU Liège	Liège		Belgium	4000
15	UC Louvain	Louvain		Belgium	1200
16	AZ Delta	Roeselare		Belgium	8800
17	CHU UCL Namur-Godinne	Yvoir		Belgium	5530