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

Covid19 Clinical Trial

— CONFIDENT  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04558476
• Other study ID #: 2020-003102-31
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 11, 2020
• Est. completion date: April 2023

Study information

• Verified date: January 2023
• Source: University of Liege
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 475
• Est. completion date: April 2023
• Est. primary completion date: April 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Corona Virus Infection
• Coronavirus Infections
• COVID-19
• Covid19
• Mechanical Ventilation Complication
• Respiratory Failure
• Respiratory Insufficiency
• SARS (Severe Acute Respiratory Syndrome)
• Severe Acute Respiratory Syndrome

Intervention

Biological:
• Convalescent Plasma
2 units of convalescent plasma

Other:
• Standard of Care
Gold Standards

Locations

Country	Name	City	State
Belgium	OLVZ Aalst	Aalst
Belgium	UZ Antwerpen	Antwerp
Belgium	Imelda ZH Bonheiden	Bonheiden
Belgium	UZ Brussel	Brussel
Belgium	CHU Saint Pierre	Brussels
Belgium	Erasme	Brussels
Belgium	CHU Charleroi Marie Curie	Charleroi
Belgium	AZ Sint Blasius	Dendermonde
Belgium	UZ Gent	Gent
Belgium	AZ Groeningen Kortrijck	Kortrijk
Belgium	CHR Citadelle	Liège
Belgium	CHU Liège	Liège
Belgium	UC Louvain	Louvain
Belgium	Clinique Saint Pierre Ottignies	Ottignies	Brabant Wallon
Belgium	AZ Delta	Roeselare
Belgium	Centre Hospitalier Wallonie Picarde	Tournai	Hainaut
Belgium	CHU UCL Namur-Godinne	Yvoir

Sponsors (2)

Lead Sponsor	Collaborator
University of Liege	KCE Belgian Healthcare Knowledge Centre

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vital status	dead or alive	at day 28
Secondary	day 90 mortality	dead or alive	at day 90
Secondary	number of ventilator-free days at day 28	to assess the ventilator free days	at day 28
Secondary	number of renal replacement therapy free days at day 28	to assess the number of renal replacement therapy free days	at day 28
Secondary	number of vasopressors free-days at day 28	to assess the number of vasopressors free-days	at day 28
Secondary	use of ECMO before day 28	to assess if ECMO was required	till day 28
Secondary	value of the SOFA score at days 7, 14 and 28	to assess the value of SOFA score	Day 1, 7, 14, 28
Secondary	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
Secondary	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
Secondary	blood C reactive protein (CRP) concentration	to assess the concentrations of C reactive protein (CRP)	Days 7, 14 and 28
Secondary	ferritin concentration	to assess the concentration of ferritin	Days 7, 14 and 28
Secondary	lymphocyte count	to assess the count of lymphocyte	Days 7, 14 and 28
Secondary	length of stay in the acute care hospital	to assess the lenght of stay in the acute care	through study completion, 1 year
Secondary	location of the patient	to assess the location of the patient : acute care hospital, post acute care hospital, long-term residency, home	Day 90
Secondary	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
Secondary	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
Secondary	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
Secondary	Transfusion related adverse events	to assess the transfusion related adverse events	till 28 days
Secondary	Determine the type of concommittent inflammatory response	assess clusters based on the profile of cytokines, chemokines and cell adhesion markers	till 28 days