Precision Medicine Adaptive Network Platform Trial in Hypoxemic Acute Respiratory Failure
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Colorado, Denver
About this trial
The goal of this trial is to accelerate the development of pharmacological therapies for critical illness by identifying biological sub phenotypes in patients with acute respiratory distress syndrome (ARDS). The trial will stratify participants by biological markers into different sub phenotypes, then randomized 1:1:1 to active treatment 1, active treatment 2, or usual care. Initial stratification will be into hyperinflammatory and hypoinflammatory sub phenotypes in ARDS based on plasma biomarker profiles. Regular adaptive analyses will enable efficient identification of treatment effects within each sub phenotype, stopping interventions where there is evidence of efficacy or futility, and bringing in new interventions and potentially new sub phenotypes.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
a known acute clinical insult or new or worsening respiratory dysfunction
receiving respiratory support via invasive mechanical ventilation or non- invasive mechanical ventilation including continuous positive airway pressure, or high flow nasal oxygen greater than or equal to 30L/min
A pandemic associated syndrome
Disqualifiers
More than 48 hours from the diagnosis of AHRF
Patient is known to be pregnant
Liver transaminases >8 times the upper limit of the normal range
Creatine kinase >10 times the upper limit of the normal range
Trial design
Design model
Parallel
Treatments tested in this trial
Simvastatin
DrugSimvastatin will be administered at a dose of 80 mg once daily by the enteral route for up to 28 days
Baricitinib
DrugBaricitinib will be administered at a dose of 4 mg once daily by the enteral route for up to 10 days.Baricitinib will be prescribed on the participants' in-patient drug administration chart (or equivalent) and administered to the participant by appropriately trained clinical staff with appropriate competencies in accordance with local practice. These staff do not need to be on the study delegation log. The dosing regimen below will be used in the setting of renal impairment: eGFR 30 to \<60 mL/min Baricitinib Dose: 2mg eGFR15 to \<30 mL/min Baricitinib Dose:1mg eGFR \<15 mL/min (or receiving RRT) Baricitinib Dose withheld
Treatment groups
300 Participants
are divided into 3 treatment groupsGroup A: Usual CareNo intervention 0 interventions
Group B: SimvastatinActive comparator 1 intervention
Group C: BaricitinibActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
28 day organ support free days
Number of days alive and free of organ support, which is defined as needing either respiratory or cardiovascular support. Respiratory support is defined as invasive mechanical ventilation or non-invasive ventilation including continuous positive airway pressure or high-flow nasal oxygen with a Fraction of inspired oxygen (FiO2) ≥ 0.4 and a flow rate ≥30L/min. Cardiovascular support is defined as the continuous infusion of any vasopressor or inotrope medication
Time frame
in- hospital through day 28Secondary outcomes
1
28 day vasopressor free days
Number of days alive and free of vasopressor use
Time frame
in-hospital through day 282
28-day respiratory support free days
Days alive and free of invasive mechanical ventilation or non-invasive ventilation including continuous positive airway pressure or high-flow nasal oxygen with an FiO2 ≥ 0.4 and a flow rate ≥30L/min
Time frame
28 days3
Receiving new renal replacement therapy
Initiation of hemodialysis, peritoneal dialysis, or continuous renal replacement therapy
Time frame
in-hospital through day 284
Progression to invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or death among those not receiving that support at baseline
New initiation of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), or death
Time frame
In-hospital through day 90Other outcomes
1
14-day Delirium and Coma-Free Days
Days alive and free of delirium, assessed by the Confusion Assessment Method for the Instensive Care Unit (CAM-ICU), and delirium, assessed by the Richmond Agitation Sedation Scale (RASS score)
Time frame
14 days2
Incidence of ICU acquired weakness.
Evaluated using the Manual Muscle Strength Testing (MMST) and handgrip strength. The MMST is a standardized, hands-on clinical assessment to measure strength and function of individual muscles or muscle groups. Handgrip strength by dynamometer measures the maximum isometric hand and forearm strength.
Time frame
Day 7 or ICU discharge and hospital discharge3
Health-related quality of life
The EQ-5D-5L is a survey tool to measure health-related quality of life, whereby a score of 100 indicates the best possible health state and a score 0 is the worst possible health state.
Time frame
90 days and 180 days4
Hospital Anxiety and Depression Scale (HADS)
HADS is a 14-item scale with 7 items each for anxiety and depression subscales. Scoring for each item ranges from 0 to 3, whereby a subscale score \>8 denotes anxiety or depression.
Time frame
90 days and 180 daysLocations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Colorado, Denver
Lead sponsor
Vanderbilt University School of Medicine
Collaborator
Emory University
Collaborator
Wake Forest University
Collaborator
New York University
Collaborator
University of California, San Francisco
Collaborator
Montefiore Medical Center
Collaborator
University of Pennsylvania
Collaborator
Intermountain Health Care, Inc.
Collaborator
Congressionally Directed Medical Research Programs
Collaborator
Source ClinicalTrials.gov
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