Anakinra, COVID-19, Cytokine Storm (SOBI)
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|ClinicalTrials.gov Identifier: NCT04603742|
Recruitment Status : Not yet recruiting
First Posted : October 27, 2020
Last Update Posted : March 25, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Covid19 Cytokine Storm Mechanical Ventilation Complication||Drug: Anakinra Drug: 0.9% Saline||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||170 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This study is a phase II double-blind, placebo-controlled, multicentered trial. Patients in the intervention arm will receive anakinra IV (N=85) 4 times a day for 7 days. The placebo arm will receive normal saline IV (N=85) 4 times a day for 7 days. The investigators will follow up with patients for up to 60 days.|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Anakinra in Adults With Severe COVID-19 and Features of Cytokine Storm Syndrome: A Randomized, Double-blind, Placebo-controlled Trial|
|Estimated Study Start Date :||July 2021|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||February 2022|
Experimental: Anakinra IV
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.
100 mg of Anakinra will be mixed with 100 mL of 0.9% saline solution for IV administration.
Other Name: Anakinra IV
Placebo Comparator: Normal Saline IV
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.
Drug: 0.9% Saline
The placebo preparation will consist of a 100 mL of 0.9% saline solution without the addition of anakinra.
Other Name: Saline IV
- Number of subjects alive without having required mechanical ventilation [ Time Frame: 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.
- 60-day mortality [ Time Frame: 60 days post randomization ]Mortality of participants will be compared between those that received anakinra and those that did not.
- Patient Hospitalization [ Time Frame: 28 days post randomization ]The number of days of hospitalization in the anakinra group compared to placebo after randomization up to day 28.
- Patient Mechanical Ventilation [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04603742
|Contact: Iris Y Navarro-Millan, MD, MSPHfirstname.lastname@example.org|
|United States, New York|
|Weill Cornell Medcine|
|New York, New York, United States, 10021|
|Contact: Iris Y Navarro-Millan, MD, MSPH 646-962-5896 email@example.com|
|Principal Investigator:||Iris Y Navarro-Millan, MD, MSPH||Weill Medical College of Cornell University|