Anakinra, COVID-19, Cytokine Storm

Phase 2

Withdrawn

• Conditions: Covid19; Cytokine Storm; Mechanical Ventilation Complication
• Interventions: Drug: 0.9% Saline; Drug: Anakinra

• Registration Number: NCT04603742
• Lead Sponsor: Weill Medical College of Cornell University

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-10-23
• Study First Posted: 2020-10-27
• Study Start: 2021-12
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-14
• Last Update Posted: 2022-01-25
• Primary Completion: 2022-06
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal Saline IV	0.9% Saline	Patients in the placebo arm will receive normal saline IV (N=85) 4 times a day for 7 days. The investigator will follow up with patients for up to 60 days.
Anakinra IV	Anakinra	Patients in the intervention arm will receive anakinra IV (N=85) 4 times a day for 7 days. The investigator will follow up with patients for up to 60 days.

Primary Outcome Measures

Name	Time	Method
Number of subjects alive without having required mechanical ventilation	28 days post randomization	This will be measured among subjects with COVID-19, features of CSS, and severe respiratory failure (WHO category 4 or 5) who are alive and without having required mechanical ventilation 28 days post randomization.

Secondary Outcome Measures

Name	Time	Method
60-day mortality	60 days post randomization	Mortality of participants will be compared between those that received anakinra and those that did not.
Patient Mechanical Ventilation	28 days post randomization	The number of days with supplemental oxygen, with noninvasive ventilation or high-flow oxygen at day 28 after randomization in the anakinra group compared to placebo.
Patient Hospitalization	28 days post randomization	The number of days of hospitalization in the anakinra group compared to placebo after randomization up to day 28.

Trial Locations

Locations (1)

Weill Cornell Medcine; 🇺🇸 New York, New York, United States