Covid-19 living Data

Ruxolitinib vs Placebo (RCT)

Hospitalized patients

Studies included but not extracted/included in the analysis: Rein L, Crit Care Med, 2022

FOREST PLOTS -2022-05-16

Studies description

Trial NCT04362137; EudraCT 2020-001662-11
Publication RUXCOVID - Han MK, Lancet Rheumatol (2022) (published paper)
Dates: 2020-05-04 to 2020-09-19
Funding: Private (Novartis and Incyte)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Russia, USA, Brazil, Spain, Argentina, Peru, Turkey, Mexico, UK, Colombia, France, and Germany Follow-up duration (days): 29
Inclusion criteria	Aged 12 years or older Hospitalised for confirmed COVID-19 (by PCR test or another rapid test from the respiratory tract) Patients had to meet at least one of: pulmonary infiltrates (chest x-ray or chest CT scan), respiratory frequency of at least 30 breaths per min, requiring supplementary oxygen, oxygen saturation of 94% or less on room air, or arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) of less than 300 mm Hg (40 kPa)
Exclusion criteria	Uncontrolled infection besides COVID-19 Currently intubated or intubated between screening and randomisation In ICU at time of randomisation On antirejection, immunosuppressant, or immunomodulatory drugs (ie, tocilizumab, ruxolitinib, canakinumab, sarilumab, or anakinra) Unable to ingest tablets at randomisation Pregnant or nursing
Interventions
	Treatment Ruxolitinib 5 mg tablets orally twice daily for 14 days with possible extension of treatment to 28 days
	Control Placebo
Participants
	Randomized participants : Placebo=145 Ruxolitinib=287
	Characteristics of participants N= 432 Mean age : NR 235 males Severity : Mild: n=141 / Moderate: n=268 / Severe: n=22 Critical: n=0
Primary outcome
	In the register Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care [ Time Frame: Day 1 - Day 29 ]
	In the report Composite of death, respiratory failure (requiring invasive mechanical ventilation), or ICU care, by day 29
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the trial registry, the study protocol, statistical analysis plan, results summary and clinical trial report were used in data extraction and assessment of risk of bias. No pre-print or published article was available. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. Immunosuppressants were not allowed as part of eligibility criteria but 58% of participants received steroids at baseline. The primary outcome indicated in registry reflects the primary outcome reported in the trial results summaries. The trial (n = 432) achieved the anticipated sample size in the original version of the registry (n = 402). Adverse and serious adverse events were not described in the registry but are reported in the protocol. This study was updated on May 11th, 2022 with data extracted from the published peer-reviewed report.

Trial NCT04377620
Publication RUXCOVID-DEVENT - RUXCOVID-DEVENT, Unpublished (2022) (preprint)

Funding: Private (Incyte Corporation)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Russia and the USA Follow-up duration (days): 28
Inclusion criteria	Participant or guardian health proxy must provide informed consent before any study assessment is performed Male or female participants aged ≥ 12 years Participants with coronavirus (SARS-CoV-2) infection confirmed ≤ 3 weeks prior to randomization by any test with local regulatory approval Participants who are intubated and receiving mechanical ventilation due to COVID-19-associated ARDS and have a PaO2/FiO2 of ≤ 300 mmHg within 6 -hours of randomization Participants with lung imaging showing bilateral or diffuse pulmonary infiltrates on chest x-ray or CT scan.
Exclusion criteria	Known history of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib Presence of severely impaired renal function defined by estimated creatinine clearance < 15 mL/min measured or calculated by Cockcroft-Gault equation or calculated by the updated bedside Schwartz equation Participants must not be receiving CRRT or intermittent hemodialysis at screening In the opinion of the investigator, unlikely to survive for > 24 hours from randomization Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19) Currently receiving ECMO Participant may not be sharing a ventilator, or co-ventilating, with any other patient Treatment with anti-IL-6, IL-6R, IL-1RA, IL-1β, or GM-CSF antagonists, or a BTK inhibitor, within 7 days of randomization Treatment with a JAK inhibitor within 30 days of randomization Participants who are on long-term use of antirejection or immunomodulatory drugs Pregnant or nursing (lactating) women.
Interventions
	Treatment Ruxolitinib 15 mg twice a day for 14 days through enteric feeding tube or orally Ruxolitinib 5mg 5 mg twice a day for 14 days through enteric feeding tube or orally Ruxolitinib 15mg 15 mg twice a day for 14 days through enteric feeding tube or orally
	Control Placebo
Participants
	Randomized participants : Ruxolitinib =164 Placebo=47 Ruxolitinib 5mg=87 Ruxolitinib 15mg=77
	Characteristics of participants N= 375 Mean age : NR 185 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=0 Critical: n=288
Primary outcome
	In the register Percentage of Participants Who Have Died Due to Any Cause [ Time Frame: Study start to Day 29 ] To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.
	In the report NR
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Not reported
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Low
General comment	“In addition to the study results posted to ClinicalTrials.gov, the protocol, statistical analysis plan and prospective study registry were used in data extraction and risk of bias assessment. No manuscript was available. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome. The eligibility age was changed from ≥18 years to ≥12 years one week after start of recruitment. The study was terminated early by the study sponsor for unknown reasons that were not related to safety. As a result the study (n=211) did not achieve the target sample size (n=500) specified in the trial registry."