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

University of Liege

Status and phase: Completed; Phase 2

Conditions: SARS (Severe Acute Respiratory Syndrome); Respiratory Failure; Corona Virus Infection; Mechanical Ventilation Complication; Covid19

Treatments: Biological: Convalescent Plasma; Other: Standard of Care

Study type: Interventional

Funder types: Other

Identifiers

NCT04558476

2020-003102-31

Details and patient eligibility

About

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.

Full 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.

Enrollment: 475 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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475 participants in 2 patient groups

Convalescent Plasma

Experimental group

Description:

2 units of plasma ( 400-500ml) from 2 different donnors duration of treatment =2 h

Treatment:

Biological: Convalescent Plasma

Standard of care

Other group

Description:

Standard of care according the last gold standards

Treatment:

Other: Standard of Care