ARDS (Acute Respiratory Distress Syndrome)Phase 2US-PANTHERNCT07779642
Precision Medicine Adaptive Network Platform Trial in Hypoxemic Acute Respiratory Failure
A Phase 2 study testing Simvastatin and Baricitinib in people with ARDS (Acute Respiratory Distress Syndrome) and Acute Hypoxic Respiratory Failure, run by University of Colorado, Denver.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ARDS (Acute Respiratory Distress Syndrome), Acute Hypoxic Respiratory Failure
- What is being tested?
- Simvastatin and Baricitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- Sep 2026to Sep 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Critically ill patients in hospital and at least 1 of the following:
- Acute respiratory distress syndrome (ARDS). ARDS as defined by:
- 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
- within the same 24-hour time period:
- 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
- A pandemic associated syndrome
Who cannot join
- Simvastatin:
- 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
- Currently receiving ongoing treatment with any of the following: itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, cyclosporine, amiodarone, verapamil, or diltiazem.
Show all 21Show fewer
- Severe renal impairment (eGFR < 30mL/min and not receiving renal replacement therapy).
- Current or recent treatment (within 2 weeks) with statins
- Physician decision that a statin is required for proven indication
- Contraindication to enteral drug administration, e.g., patients with mechanical bowel obstruction. Patients with high gastric aspirates due to an ileus are not excluded.
- Known hypersensitivity to simvastatin
- Baricitinib
- 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
- Absolute neutrophil count less than 0.5x10 9/L
- Currently receiving ongoing immunosuppressants (high dose corticosteroids, B and T cell targeted therapies, interferon, or JAK inhibitors)
- Severe renal impairment (eGFR < 15mL/min) or receiving renal replacement therapy
- Known active tuberculosis infection or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines.
- Contraindication to enteral drug administration, e.g., patients with mechanical bowel obstruction. Patients with high gastric aspirates due to an ileus are not excluded.
- Known hypersensitivity to baricitinib
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the detailed description
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.
- Being tested
- Simvastatin, Baricitinib
- Keywords
- ARDS, acute hypoxic respiratory failure
- Medical subject headings
- Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Simvastatin will be administered at a dose of 80 mg once daily by the enteral route for up to 28 days
BaricitinibDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Usual Care | No intervention | 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 | Active comparator | Simvastatin will be administered at a dose of 80 mg once daily by the enteral route for up to 28 days Receives: Drug: Simvastatin |
| Baricitinib | Active comparator | 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 Receives: Drug: Baricitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: in- hospital through day 28
Secondary outcomes (21)
28 day vasopressor free days
Number of days alive and free of vasopressor use
Measured: 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
Measured: 28 days
Receiving new renal replacement therapy
Initiation of hemodialysis, peritoneal dialysis, or continuous renal replacement therapy
Measured: 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
Measured: In-hospital through day 90
ICU length of stay
Number of days alive and requiring ICU-level of care
Measured: in-hospital through day 90
Hospital length of stay
Number of days alive and in the hospitalized
Measured: In-hospital through day 90
All-cause mortality
The total number of deaths from any reason
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 28 days
Stroke
number of occurrences of a stroke, defined as a sudden interruption of blood flow to the brain, either ischemic or hemorrhagic
Measured: 28 days
Myocardial infarction
Number of occurrences of a myocardial infarction, defined interruption or blockage of blood flow to the heart.
Measured: 28 days
Ischemic bowel
number of occurrences of an ischemic bowel, defined as blood flow to the intestines that has slowed or stopped.
Measured: 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.
Measured: 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
Measured: 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
Measured: 90 days
Physical function (SPPB) at hospital discharge
The Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremity functioning.
Measured: 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
Measured: Hospital discharge, day 90, day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2029 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for ARDS (Acute Respiratory Distress Syndrome)Studies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Platform Trial, Bayesian Design. The adaptive design will allow for interventions to stop where there is evidence of efficacy or futility and new interventions and new sub-phenotypes. The trial will start with 3 arms, 2 intervention arms and a usual care arm. Each intervention arm is compared to usual care of ICU patients.
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt University School of Medicine, Emory University, Wake Forest University, New York University, University of California, San Francisco, Montefiore Medical Center, University of Pennsylvania, Intermountain Health Care, Inc., Congressionally Directed Medical Research Programs
- Responsible party
- Sponsor
- Investigators
- Neil Aggarwal, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07779642
- Sponsor's protocol ID
- 26-0523
- Other IDs
- HT94252510958, CDMRP-eBRAP PR240149
- Acronym
- US-PANTHER
- Status last verified
- Oct 2026
- First submitted
- 18 Aug 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dimairo M, Pallmann P, Wason J, Todd S, Jaki T, Julious SA, Mander AP, Weir CJ, Koenig F, Walton MK, Nicholl JP, Coates E, Biggs K, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG; ACE Consensus Group. The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. Trials. 2020 Jun 17;21(1):528. doi: 10.1186/s13063-020-04334-x.
PubMed 32546273McNamee JJ, Gillies MA, Barrett NA, Perkins GD, Tunnicliffe W, Young D, Bentley A, Harrison DA, Brodie D, Boyle AJ, Millar JE, Szakmany T, Bannard-Smith J, Tully RP, Agus A, McDowell C, Jackson C, McAuley DF; REST Investigators. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial. JAMA. 2021 Sep 21;326(11):1013-1023. doi: 10.1001/jama.2021.13374.
PubMed 34463700McAuley DF, Laffey JG, O'Kane CM, Perkins GD, Mullan B, Trinder TJ, Johnston P, Hopkins PA, Johnston AJ, McDowell C, McNally C; HARP-2 Investigators; Irish Critical Care Trials Group. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014 Oct 30;371(18):1695-703. doi: 10.1056/NEJMoa1403285. Epub 2014 Sep 30.
PubMed 25268516Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS; ARDS Network. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med. 2017 Feb 1;195(3):331-338. doi: 10.1164/rccm.201603-0645OC.
PubMed 27513822Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014 Aug;2(8):611-20. doi: 10.1016/S2213-2600(14)70097-9. Epub 2014 May 19.
PubMed 24853585Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O'Kane CM, McAuley DF; Irish Critical Care Trials Group. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018 Sep;6(9):691-698. doi: 10.1016/S2213-2600(18)30177-2. Epub 2018 Aug 2.
PubMed 30078618Maslove DM, Tang B, Shankar-Hari M, Lawler PR, Angus DC, Baillie JK, Baron RM, Bauer M, Buchman TG, Calfee CS, Dos Santos CC, Giamarellos-Bourboulis EJ, Gordon AC, Kellum JA, Knight JC, Leligdowicz A, McAuley DF, McLean AS, Menon DK, Meyer NJ, Moldawer LL, Reddy K, Reilly JP, Russell JA, Sevransky JE, Seymour CW, Shapiro NI, Singer M, Summers C, Sweeney TE, Thompson BT, van der Poll T, Venkatesh B, Walley KR, Walsh TS, Ware LB, Wong HR, Zador ZE, Marshall JC. Redefining critical illness. Nat Med. 2022 Jun;28(6):1141-1148. doi: 10.1038/s41591-022-01843-x. Epub 2022 Jun 17.
PubMed 35715504Boyle AJ, McDowell C, Agus A, Logan D, Stewart JD, Jackson C, Mills J, McNamee JJ, McAuley DF. Acute hypoxaemic respiratory failure after treatment with lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal: long-term outcomes from the REST randomised trial. Thorax. 2023 Aug;78(8):767-774. doi: 10.1136/thorax-2022-218874. Epub 2022 Oct 5.
PubMed 36198573Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.
PubMed 21470008Dowdy DW, Eid MP, Dennison CR, Mendez-Tellez PA, Herridge MS, Guallar E, Pronovost PJ, Needham DM. Quality of life after acute respiratory distress syndrome: a meta-analysis. Intensive Care Med. 2006 Aug;32(8):1115-24. doi: 10.1007/s00134-006-0217-3. Epub 2006 Jun 17.
PubMed 16783553Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
PubMed 26903337Gorman EA, O'Kane CM, McAuley DF. Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management. Lancet. 2022 Oct 1;400(10358):1157-1170. doi: 10.1016/S0140-6736(22)01439-8. Epub 2022 Sep 4.
PubMed 36070788
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Medicine Adaptive Network Platform Trial in Hypoxemic Acute Respiratory Failure
- ClinicalTrials.gov ID
- NCT07779642
- Acronym / sponsor ID
- US-PANTHER / 26-0523
- Keywords
- ARDS, acute hypoxic respiratory failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Vanderbilt University School of Medicine, Emory University, Wake Forest University, New York University, University of California, San Francisco, Montefiore Medical Center, University of Pennsylvania, Intermountain Health Care, Inc., Congressionally Directed Medical Research Programs
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2029 (estimated)
- Study completion
- Sep 2030 (estimated)
- First posted
- 21 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Platform Trial, Bayesian Design. The adaptive design will allow for interventions to stop where there is evidence of efficacy or futility and new interventions and new sub-phenotypes. The trial will start with 3 arms, 2 intervention arms and a usual care arm. Each intervention arm is compared to usual care of ICU patients.
| Arm | Type | Receives |
|---|---|---|
| Usual Care | No intervention | –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 | Active comparator | Drug: SimvastatinSimvastatin will be administered at a dose of 80 mg once daily by the enteral route for up to 28 days |
| Baricitinib | Active comparator | Drug: BaricitinibBaricitinib 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Acute respiratory distress syndrome (ARDS). ARDS as defined by:
- A pandemic associated syndrome
Key exclusion criteria (21 listed)
- 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
- Currently receiving ongoing treatment with any of the following: itraconazole, ketoconazole, HIV protease inhibitors, nefazodone, cyclosporine, amiodarone, verapamil, or diltiazem.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SimvastatinSimvastatin will be administered at a dose of 80 mg once daily by the enteral route for up to 28 days | Drug | Simvastatin |
| BaricitinibBaricitinib 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 |
Primary outcome
28 day organ support free days
Time frame: in- hospital through day 28
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
21 secondary outcomes
28 day vasopressor free days
Time frame: in-hospital through day 28
28-day respiratory support free days
Time frame: 28 days
Receiving new 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
Time frame: In-hospital through day 90
ICU length of stay
Time frame: in-hospital through day 90
Hospital length of stay
Time frame: In-hospital through day 90
All-cause mortality
Time frame: In-hospital through Day 28 and day 90
Elevated Creatine Kinase 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
Time frame: 28 days
Severe thrombocytopenia, out of keeping with clinical disease
Time frame: 28 days
Severe neutropenia, out of keeping with clinical disease
Time frame: 28 days
Serious infection defined as a positive blood cultures requiring treatment.
Time frame: 28 days
Venous thromboembolism
Time frame: 28 days
Stroke
Time frame: 28 days
Myocardial infarction
Time frame: 28 days
Ischemic bowel
Time frame: 28 days
Gastrointestinal perforation
Time frame: 28 days
Clinically important gastrointestinal bleeding.
Time frame: 28 days
Serious adverse events
Time frame: 90 days
Physical function (SPPB) at hospital discharge
Time frame: Hospital discharge
Cognitive function Montreal Cognitive Assessment (MoCA)
Time frame: Hospital discharge, day 90, day 180
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Background: PubMed 32546273Dimairo M, Pallmann P, Wason J, Todd S, Jaki T, Julious SA, Mander AP, Weir CJ, Koenig F, Walton MK, Nicholl JP, Coates E, Biggs K, Hamasaki T, Proschan MA, Scott JA, Ando Y, Hind D, Altman DG; ACE Consensus Group. The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. Trials. 2020 Jun 17;21(1):528. doi: 10.1186/s13063-020-04334-x.
- Background: PubMed 34463700McNamee JJ, Gillies MA, Barrett NA, Perkins GD, Tunnicliffe W, Young D, Bentley A, Harrison DA, Brodie D, Boyle AJ, Millar JE, Szakmany T, Bannard-Smith J, Tully RP, Agus A, McDowell C, Jackson C, McAuley DF; REST Investigators. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial. JAMA. 2021 Sep 21;326(11):1013-1023. doi: 10.1001/jama.2021.13374.
- Background: PubMed 25268516McAuley DF, Laffey JG, O'Kane CM, Perkins GD, Mullan B, Trinder TJ, Johnston P, Hopkins PA, Johnston AJ, McDowell C, McNally C; HARP-2 Investigators; Irish Critical Care Trials Group. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014 Oct 30;371(18):1695-703. doi: 10.1056/NEJMoa1403285. Epub 2014 Sep 30.
- Background: PubMed 27513822Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, Calfee CS; ARDS Network. Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy. Am J Respir Crit Care Med. 2017 Feb 1;195(3):331-338. doi: 10.1164/rccm.201603-0645OC.
- Background: PubMed 24853585Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA; NHLBI ARDS Network. Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med. 2014 Aug;2(8):611-20. doi: 10.1016/S2213-2600(14)70097-9. Epub 2014 May 19.
- Background: PubMed 30078618Calfee CS, Delucchi KL, Sinha P, Matthay MA, Hackett J, Shankar-Hari M, McDowell C, Laffey JG, O'Kane CM, McAuley DF; Irish Critical Care Trials Group. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir Med. 2018 Sep;6(9):691-698. doi: 10.1016/S2213-2600(18)30177-2. Epub 2018 Aug 2.
- Background: PubMed 35715504Maslove DM, Tang B, Shankar-Hari M, Lawler PR, Angus DC, Baillie JK, Baron RM, Bauer M, Buchman TG, Calfee CS, Dos Santos CC, Giamarellos-Bourboulis EJ, Gordon AC, Kellum JA, Knight JC, Leligdowicz A, McAuley DF, McLean AS, Menon DK, Meyer NJ, Moldawer LL, Reddy K, Reilly JP, Russell JA, Sevransky JE, Seymour CW, Shapiro NI, Singer M, Summers C, Sweeney TE, Thompson BT, van der Poll T, Venkatesh B, Walley KR, Walsh TS, Ware LB, Wong HR, Zador ZE, Marshall JC. Redefining critical illness. Nat Med. 2022 Jun;28(6):1141-1148. doi: 10.1038/s41591-022-01843-x. Epub 2022 Jun 17.
- Background: PubMed 36198573Boyle AJ, McDowell C, Agus A, Logan D, Stewart JD, Jackson C, Mills J, McNamee JJ, McAuley DF. Acute hypoxaemic respiratory failure after treatment with lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal: long-term outcomes from the REST randomised trial. Thorax. 2023 Aug;78(8):767-774. doi: 10.1136/thorax-2022-218874. Epub 2022 Oct 5.
- Background: PubMed 21470008Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.
- Background: PubMed 16783553Dowdy DW, Eid MP, Dennison CR, Mendez-Tellez PA, Herridge MS, Guallar E, Pronovost PJ, Needham DM. Quality of life after acute respiratory distress syndrome: a meta-analysis. Intensive Care Med. 2006 Aug;32(8):1115-24. doi: 10.1007/s00134-006-0217-3. Epub 2006 Jun 17.
- Background: PubMed 26903337Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291.
- Background: PubMed 36070788Gorman EA, O'Kane CM, McAuley DF. Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management. Lancet. 2022 Oct 1;400(10358):1157-1170. doi: 10.1016/S0140-6736(22)01439-8. Epub 2022 Sep 4.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Neil Aggarwal, MD principal investigator
University of Colorado, Denver
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simvastatin and Baricitinib in people with ARDS (Acute Respiratory Distress Syndrome) and Acute Hypoxic Respiratory Failure, run by University of Colorado, Denver.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carrie B Higgins, BSN (3037240961, carrie.higgins@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
28 day organ support free days (time frame: in- hospital through day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07779642, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.