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.
Summary of results |
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The COV-AID study involved 342 patients hospitalised in 16 Belgian hospitals for COVID-19. As soon as the first signs of a cytokine storm appeared," explains Prof. Lambrecht, "we administered the drugs, alone or in pairs, in addition to the standard treatment. We compared their progress with that of 76 other patients (the control group) who received only the standard treatment, i.e. oxygen and the anti-inflammatory dexamethasone". The results of the COV-AID study do not confirm the wisdom of using these anti-rheumatic drugs, and even cast doubt on them. In fact, although there was a marked reduction in the inflammation parameters in the blood of patients receiving anti-rheumatic drugs, this treatment had no effect on the speed with which they recovered, even for the sickest patients. They had to be admitted to intensive care as often as those in the control group, they remained as dependent on oxygen and artificial respiration for as long, and their chances of survival were no better |
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 |
Sponsor |
UZ Gent |
Chief Investigator |
Prof. Dr. Bart Lambrecht
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Participating sites |
16 hospitals in Belgium |
External Partners |
NAP |
Protocol | Download protocol View publication Trials |
Results | View publication The Lancet Respiratory Disease Download press release (FR NL) Download report |
For timelines and recruitment, see dashboard
Clinicaltrials.gov: NCT04330638
EudraCT: 2020-001500-41