NCT04603742

Anakinra, COVID-19, Cytokine Storm

Anakinra in Adults With Severe COVID-19 and Features of Cytokine Storm Syndrome: A Randomized, Double-blind, Placebo-controlled Trial

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Weill Medical College of Cornell University · Academic / Other
• Sex: All
• Age: 18 Years – 89 Years
• Healthy volunteers: Not accepted

Summary

The clinical syndrome associated with infection of the Coronavirus Disease 2019 (COVID-19) is notable for its variable clinical expression. Infection and transmission of the virus by asymptomatic individuals have been noted and represent one end of the clinical spectrum, while multi-organ failure, particularly pulmonary failure, and death represent the most severe end of the clinical spectrum. In a recent study published from the investigator's institution about the first 393 patients with COVID-19, 77.1% had a fever, a mechanism driven by IL-1. This suggests that there may be an excess release of IL-1 present. Cytokine storm syndrome (CSS) has been observed in patients with COVID-19 and has been proposed to contribute to the acute pulmonary failure that occurs. In distinct clinical settings, macrophage activation syndrome, elevated levels of pro-inflammatory cytokines, including IL-1, IL-6, and others, as well as elevations in laboratory indicators, including ferritin, CRP, d-dimer, and lymphopenia, have been observed. IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses. Anakinra, a recombinant IL-1 receptor antagonist, has shown promise in treating CSS. It inhibits both IL-1-alpha and IL-1-beta. It is an FDA approved medication used in rheumatoid arthritis (RA) and Cryopyrin-Associated Periodic Syndromes (CAPS). Anakinra's ability to inhibit both IL-1 subtypes and short half-life makes it favorable to some experts. In the investigator's case-series, using anakinra in patients with COVID-19 showed promising in preventing the need for mechanical ventilation, and mortality subsequently. This study will determine the efficacy of anakinra, an interleukin (IL) -1 receptor blocker, in reducing the need for mechanical ventilation and/or 28-day mortality among patients with COVID-19 who have features of CSS and severe respiratory failure. The investigators will test the hypothesis that the proportion of subjects with COVID-19, features of CSS, and severe respiratory failure (World Health Organization (WHO) category 4 or 5) alive and without having required mechanical ventilation at day 28 from randomization will be 18% higher among those that receive anakinra compared to those that receive a placebo. A secondary hypothesis is that the number of subjects alive at 60-days will be higher amongst those who receive anakinra compared to those who receive a placebo.

Conditions

• Covid19
• Cytokine Storm
• Mechanical Ventilation Complication

Interventions

Type	Name	Description
DRUG	Anakinra	100 mg of Anakinra will be mixed with 100 mL of 0.9% saline solution for IV administration.
DRUG	0.9% Saline	The placebo preparation will consist of a 100 mL of 0.9% saline solution without the addition of anakinra.

Timeline

• Start date: 2021-12-01
• Primary completion: 2022-06-01
• Completion: 2022-09-01
• First posted: 2020-10-27
• Last updated: 2022-01-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study