A Phase 2 interventional study of Simvastatin and Baricitinib in ARDS (Acute Respiratory Distress Syndrome) and Acute Hypoxic Respiratory Failure, sponsored by University of Colorado, Denver. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by University of Colorado, Denver · Phase 2, Interventional, and Treatment
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.
The primary objective of this trial is to accelerate the development of pharmacological therapies for critical illness by establishing an adaptive platform trial to test the efficacy of prioritized pharmacological interventions in patients with acute respiratory distress syndrome (ARDS). Participants will be recruited from multiple sites within the United States.
ARDS is defined by:
A known acute clinical insult or new or worsening respiratory dysfunction, and Receipt of respiratory support via invasive mechanical ventilation or non-invasive ventilation including continuous positive airway pressure, or high-flow nasal oxygen ≥30L/min, and
Within the same 24-hour time period:
Bilateral opacities on chest imaging not fully explained by effusions, lobar/lung collapse/atelectasis, or nodules, and Respiratory failure not fully explained by cardiac failure, fluid overload, pulmonary embolism, acute airways disease, or interstitial lung disease and Pa02/Fi02 ration \<40 kPa from arterial blood gases, or Sp02/Fi02 \<315 from pulse oximetry where Sp02 \<97.
The time of onset of ARDS is when the last criterion in 3 is met.
Developing effective pharmacological therapies for ARDS will improve patient outcomes in an area of significant unmet need as well as reduce health care costs. Survivors of ARDS experience reduced health-related quality of life, with substantial health care and societal costs. Secondary analyses of prior randomized clinical trials have suggested different treatment responses between biological sub phenotypes in patients with ARDS.
A new paradigm in critical care suggests that de-emphasizing clinical syndromic definitions and focusing instead on sub phenotypes more closely linked to the host biological response is the key to identifying effective therapeutics. Using syndromic definitions does not provide information on which subgroups of patients are likely to respond effectively and safely to a given pharmacological treatment.
Initially, the platform will use the hyper and hypoinflammatory sub phenotypes in ARDS that are characterized by differing levels of systemic inflammation, clinical features, and treatment responses. Hyper and hypoinflammatory phenotyping will be determined using validated assays for IL-6 and sTNFR1. These measurements will be combined with measurement of the lowest bicarbonate level within the proceeding 24 hours from a plasma or an arterial blood gas and the data used to determine phenotype in real time at the bedside using a validated algorithm. Thus, sub phenotyping will occur via collection and real-time processing of plasma biomarkers after inclusion criteria are met and prior to randomization.
The ELLA Device (Bio-Techne) is a fully automated immune-analyzer that enables on-site simultaneous detection of analytes from a single sample of blood. As a minimal risk procedure for the participant and user, a sample of less than 1 mL of fresh blood from the consented participant is required. The results are generated typically within 60-80 minutes, and biomarker values for IL-6 and sTNFR1, along with the lowest blood bicarbonate level in the previous 24 hours, are entered into a logistic regression model to identify the probability of belonging to the hyperinflammatory sub phenotype. Participants and clinical teams will not be aware of the participant's real-time sub phenotype.
This trial is open-label whereby participants, the clinical team and study team will not be masked to the intervention. Randomization will be balanced with equal ratios between usual care and each intervention participants are eligible for, i.e. a 1:1:1 ratio (usual care versus intervention (where eligible) by sub phenotype). There is no fixed sample size, but we have capped the sample size for the initial treatments and sub phenotype, and will stop enrollment when results indicate efficacy or futility. Every participant will have additional blood collected at trial enrollment (day 0), day 2, and day 6.
Participants will be followed by the clinical research team daily whilst in the ICU.
Once the participants have left ICU and been discharged to acute care, they will be followed prior to hospital discharge. They will also be followed up by telephone or electronically 90 days and 180 days after randomization (+14 days). Survival status will be entered at 365 days.
382 studies on the registry are indexed under Acute Lung Injury; 73 are open to participants now.
This study's planned enrollment of 300 is above the median of 60 across 227 interventional studies indexed under Acute Lung Injury.
Browse Acute Lung Injury studies →University of Colorado, Denver is the lead sponsor of 1,543 studies on the registry; 317 are open to participants now.
Of its 147 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Critically ill patients in hospital and at least 1 of the following:
Acute respiratory distress syndrome (ARDS). ARDS as defined by:
i. bilateral opacities on chest imaging not fully explained by effusion, lobar/lung collapse/atelectasis, or nodules ii. respiratory failure not fully explained by cardiac failure, fluid overload, pulmonary embolism, acute airway disease iii. Pa02/Fi02 ration \<40 kPa from arterial blood gases, or Sp02 \<315 from pulse oximetry where Sp02 \<97
Exclusion criteria:
Simvastatin:
Baricitinib
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Usual care of ICU patients with ARDS. Patients randomized to the control arm or usual care will not receive simvastatin or baricitinib for 28 days or discharge from the ICU.
Simvastatin will be administered at a dose of 80 mg once daily by the enteral route for up to 28 days
Drug: Simvastatin
Baricitinib 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
Drug: Baricitinib
Simvastatin will be administered at a dose of 80 mg once daily by the enteral route for up to 28 days
Baricitinib 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
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 28
28 day vasopressor free days
Number of days alive and free of vasopressor use
Time frame: in-hospital through day 28
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 days
Receiving new renal replacement therapy
Initiation of hemodialysis, peritoneal dialysis, or continuous renal replacement therapy
Time frame: in-hospital through day 28
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 90
ICU length of stay
Number of days alive and requiring ICU-level of care
Time frame: in-hospital through day 90
Hospital length of stay
Number of days alive and in the hospitalized
Time frame: In-hospital through day 90
All-cause mortality
The total number of deaths from any reason
Time frame: In-hospital through Day 28 and day 90
Elevated Creatine Kinase more than 10 times the upper limit of normal
Number of occurrences in which creatinine kinase is elevated more than 10 times the upper limit of normal.
Time frame: 28 days
Alanine Transaminase or Aspartate Transaminase more than 8 times the upper limit of normal
Number of occurrences in which alanine transaminase (ALT) or aspartate transaminase (AST) more than 8 times the upper limit of normal.
Time frame: 28 days
Severe thrombocytopenia, out of keeping with clinical disease
Number of occurrences where the platelet count is lower than expected trajectory for a known clinical disease course.
Time frame: 28 days
Severe neutropenia, out of keeping with clinical disease
Number of occurrences in which low neutrophil count is lower than expected trajectory for a known clinical disease course.
Time frame: 28 days
Serious infection defined as a positive blood cultures requiring treatment.
Number of occurrences of a serious infection, defined as a positive blood culture that requires treatment, and pulmonary aspergillosis that requires treatment
Time frame: 28 days
Venous thromboembolism
Number of occurrences of a venous thromboembolism defined as a condition where a blood clot forms in a non-superficial vein
Time frame: 28 days
Stroke
number of occurrences of a stroke, defined as a sudden interruption of blood flow to the brain, either ischemic or hemorrhagic
Time frame: 28 days
Myocardial infarction
Number of occurrences of a myocardial infarction, defined interruption or blockage of blood flow to the heart.
Time frame: 28 days
Ischemic bowel
number of occurrences of an ischemic bowel, defined as blood flow to the intestines that has slowed or stopped.
Time frame: 28 days
Gastrointestinal perforation
number of occurrences of gastrointestinal (GI) perforation, defined as a hole that has formed all the way through the wall of the stomach, small intestine, or large intestine.
Time frame: 28 days
Clinically important gastrointestinal bleeding.
Number of occurrences of clinically important GI bleeding, defined as overt bleeding on GI endoscopy, developing as a complication in the ICU and accompanied by 1 or more of the following features within 24 hours: Spontaneous drop of systolic, mean arterial pressure or diastolic blood pressure of 20mmHg or more Start of vasopressor or a 20% increase in vasopressor dose Decrease in hemoglobin of at least 2 g/dl Transfusion of 2 units of packed red blood cells (PRBCs) or more
Time frame: 28 days
Serious adverse events
Number of occurrences of a serious adverse event (SAE), defined as any event that * Results in death; * Is life-threatening * Requires hospitalization or prolongation of existing inpatient's hospitalization * Results in persistent or significant disability or incapacity * Is a congenital abnormality or birth defect
Time frame: 90 days
Physical function (SPPB) at hospital discharge
The Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremity functioning.
Time frame: Hospital discharge
Cognitive function Montreal Cognitive Assessment (MoCA)
Completion of the mini-Montreal Cognitive Assessment (mini-MoCA), a tool for early detection of mild cognitive impairment. MoCA accurately and quickly assesses short term memory, visuospatial abilities, executive functions, attention, concentration and working memory, language, and orientation to time and place
Time frame: Hospital discharge, day 90, day 180
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 days
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 discharge
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 days
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 days
Social and Wellbeing
Social and wellbeing as measured by the 36-Item Short Form Health Survey (SF-36): a patient-reported survey that measures general health and quality of life.
Time frame: 90 days and 180 days
Impact of events scale (6 item) at 90 days and 180 days
The Impact of Event Scale-6 (IES-6) is a short, 6-item version of the IES-R, which is used to quickly screen for post-traumatic stress disorder (PTSD) symptoms.
Time frame: 90 days and 180 days
No study locations are listed for this record.
Plan to share: Undecided
Start is estimated for Sep 2026; primary completion for Sep 2029, 36 months later.
Of 22 phase 2 interventional studies under Acute Lung Injury, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 60. This study's planned 36 months is close to that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Simvastatin · Baricitinib
University of Colorado, Denver →