COV201002: A prospective, randomized interventional study to assess the safety and efficacy of interleukin-6 and interleukin-1 pathway blockade in COVID-19 patients with acute hypoxic respiratory failure and systemic cytokine release syndrome (COV-AID)

Summary (French or Dutch)

COVID-19 (coronavirus) infection can be accompanied by severe respiratory distress and lung failure in some people due to damage to the lungs caused by the virus.
More and more doctors and researchers believe that serious COVID-19 infections are actually accompanied by an exaggerated reaction by the immune system. The inflammatory reaction, the primary role of which is to neutralize the virus, is then so strong that it damages the lung. These lung lesions are due to substances produced during any inflammatory reaction, which are called interleukins (or cytokines), and which are also responsible for fever and feelings of discomfort (to be sore everywhere).
In rheumatoid arthritis, an inflammatory disease of the joints, powerful drugs which block the action of these interleukins have been used for quite a long time, such as Kineret®, Roactemra® and Sylvant®, which block interleukin 1 and interleukin 6. Recent researches have shown that it is precisely these interleukins that are produced in too large quantities in patients with COVID-19.
The objective of this study is to determine whether a single injection of Siltuximab (Sylvant®) or Tocilizumab (Roactemra®), medicines for rheumatoid arthritis, in combination or not with a daily subcutaneous injection of Anakinra (Kineret® ), improves the condition of patients with COVID-19 and suffering from acute respiratory distress. The study will assess the efficacy and safety of these drugs, and try to understand their mechanisms of action.
 

Trial Description
Title

A prospective, randomized interventional study to assess the safety and efficacy of interleukin-6 and interleukin-1 pathway blockade in COVID-19 patients with acute hypoxic respiratory failure and systemic cytokine release syndrome (COV-AID)

Participants (P)

Hospitalised adult patients with COVID-19 infection and acute hypoxia
Presence of hypoxia defined as ratio PaO2/FiO2 below 350 and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high LDH or deep lymphopenia
Patients who have not been on mechanical ventilation for more than 24h before randomisation.

Intervention (I)

SoC + Anakinra (Group B)
SoC + Siltuximab (Group C)
SoC + Siltuximab + Anakinra (Group D)
SoC + Tocilizumab (Group E)
SoC + Tocilizumab + Anakinra (Group F)

Control (C)

Standard of Care (SOC) – (Group A)

Outcome (O)

Study if blockade of IL-6 +/- IL-1 to block the cytokine storm and acute lung injury in comparison with usual care reduces time to clinical improvement as defined by an increase of more than 2 on the 6 point ordinal scale or discharge from the hospital

Trial Design

2 by 2 factorial design
Prospective, multi-centre randomized, open label study

Sample Size

342 patients randomised

Trial duration

 13 months

Budget

€ 2.43 million

Status

Open to recruitment

 

Trial team

Sponsor

UZ Gent

Chief Investigator

Prof. Dr. Bart Lambrecht

 

Participating sites

16 hospitals in Belgium

External Partners

NAP

Documents
Protocol  
Report

Q2 2021

Publication

 

References

Clinicaltrials.gov: NCT04330638

Webpage: