Clinical trial NCT04558476: Efficacy of CONvalescent Plasma in Patients With COVID-19 Treated With Mechanical Ventilation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Mechanical Ventilation Complication
Corona Virus Infection
Respiratory Failure
SARS (Severe Acute Respiratory Syndrome)
Keywords: Covid 19
Convalescent plasmatherapy
SARS Cov-2 pneumonia
Lead sponsor: University of Liege
Sponsor class: OTHER
Collaborators: name: KCE Belgian Healthcare Knowledge Centre
First posted: 2020-09-22
Enrollment: 475
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Vital status
timeFrame: at day 28
Secondary outcomes:
measure: day 90 mortality
timeFrame: at day 90
measure: number of ventilator-free days at day 28
timeFrame: at day 28
measure: number of renal replacement therapy free days at day 28
timeFrame: at day 28
measure: number of vasopressors free-days at day 28
timeFrame: at day 28
measure: use of ECMO before day 28
timeFrame: till day 28
measure: value of the SOFA score at days 7, 14 and 28
timeFrame: Day 1, 7, 14, 28
measure: changes in SOFA scores (delta SOFA) over 7, 14 and 28 days
timeFrame: Day 7, 14 and 28 days
measure: assessment of the SARS-CoV-2 viral load
timeFrame: Days 7, 14 and 28
measure: blood C reactive protein (CRP) concentration
timeFrame: Days 7, 14 and 28
measure: ferritin concentration
timeFrame: Days 7, 14 and 28
measure: lymphocyte count
timeFrame: Days 7, 14 and 28
measure: length of stay in the acute care hospital
timeFrame: through study completion, 1 year
measure: location of the patient
timeFrame: Day 90
measure: Katz Index of independence in Activity Day Living functional score
timeFrame: Day 90 and 365
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: Day 90 and 365
measure: Quality of life scale EQ-5D-5L
timeFrame: Day 90 and 365
measure: Transfusion related adverse events
timeFrame: till 28 days
measure: Determine the type of concommittent inflammatory response
timeFrame: till 28 days
Other outcomes:
Locations:
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre Ottignies
state: Brabant Wallon
city: Tournai
country: Belgium
facility: Centre Hospitalier Wallonie Picarde
state: Hainaut
city: Aalst
country: Belgium
facility: OLVZ Aalst
city: Antwerp
country: Belgium
facility: UZ Antwerpen
city: Bonheiden
country: Belgium
facility: Imelda ZH Bonheiden
city: Brussels
country: Belgium
facility: CHU Saint Pierre
city: Brussels
country: Belgium
facility: Erasme
city: Brussel
country: Belgium
facility: UZ Brussel
city: Charleroi
country: Belgium
facility: CHU Charleroi Marie Curie
city: Dendermonde
country: Belgium
facility: AZ Sint Blasius
city: Gent
country: Belgium
facility: UZ Gent
city: Kortrijk
country: Belgium
facility: AZ Groeningen Kortrijck
city: Liège
country: Belgium
facility: CHR Citadelle
city: Liège
country: Belgium
facility: CHU Liège
city: Louvain
country: Belgium
facility: UC Louvain
city: Roeselare
country: Belgium
facility: AZ Delta
city: Yvoir
country: Belgium
facility: CHU UCL Namur-Godinne
Study officials:
References:
citation: 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.