Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome (PETARDS)

Platform adaptive embedded trial for acute respiratory distress syndrome (PETARDS) is a randomized, embedded, multifactorial, adaptive platform trial for ARDS. The study aimed to assess the impact of multiple interventions on outcomes in patients with ARDS admitted to the ICU.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Device: protective ventilation; Behavioral: prone position ventilation; Drug: glucocorticoid therapy; Other: restrictive fluid resuscitation; Biological: Thymosin Alpha; Drug: Muscle relaxant therapy; Other: Integrated Chinese and Western Medicine Treatment; Drug: statin therapy; Combination product: anti-infective treatment; Device: Extracorporeal Membrane Oxygenation（ECMO）; Genetic: stem cell therapy; Drug: Sedative analgesia/muscle relaxant therapy; Drug: inotropes therapy; Drug: Vasoactive drug therapy

Detailed Description

Mortality is significantly higher in ARDS patients requiring intensive care unit (ICU) admission.

ARDS patients admitted to the ICU typically receive multiple (as many as 10 or 20) treatments that work together to fight infection, reduce pulmonary exudation, improve oxygenation, and support systemic organ function. Clinicians are often willing to choose the exact or considered safe and effective regimen from the therapies mentioned above. Still, there are individual differences in ARDS patients, and it is difficult to confirm the optimal treatment plan. It is inevitable to choose treatment without evidence-based medicine based on experience. The primary purpose of this study was to help physicians select the best-effective approach among existing ARDS therapies, and secondly to provide a rationale for specific empirical or emerging ARDS treatments.

Clinical evidence to guide optimal management is best obtained from randomized controlled trials (RCTs); however, ARDS is a multi-causal, clinically and therapeutically heterogeneous clinical syndrome with rapid disease progression and complex clinical manifestations, in fact, difficult to organize RCT trials. In cases where the timing of onset and the pathophysiological mechanism cannot be determined, the initial treatment is the selection of protective ventilation/controlled infusion as the first-line standard therapy according to the Berlin classification of ARDS, and some second-line treatments with potential clinical benefit. It is difficult to conduct objective, scientific and timely evaluation, and the overall treatment plan is inevitably blind and empirical. This clinical operation mode is likely related to ARDS-related RCT research results. The results are unsatisfactory, the treatment response heterogeneity is high, and the outcome events vary greatly. closely related to the clinical status. The adaptive platform trial PETARDS is ideal for evaluating the effects of highly heterogeneous ARDS treatment strategies.

This clinical research design (adaptive platform trial, APT) can use the information of patients who are participating in the study to guide the clinical treatment of subsequent newly enrolled patients.

The APT trial randomized patients into multiple domains for multiple interventions to assess their effectiveness in different patients. The term "domain" refers to a common treatment unit (eg, steroid therapy) within which patients can be randomly assigned to several interventional (dose) groups (including controls, such as no steroids, as appropriate). Certainly). All trial procedures consist of a primary or "core" protocol and multiple secondary protocols, and the standard protocols, clinical treatment adaptations, and trial management and practices for specific treatment units are managed in a unified manner for each treatment unit. The core protocol, secondary protocols, and Statistical Analysis Plan (SAP) of this trial are presented in the appendix; the study required approval from the relevant ethics committees of all participating hospitals and was conducted by good clinical practice guidelines and principles described in the Declaration of Helsinki.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhaocai Zhang, Doctor; Phone Number: +86-13758131998; Email: 2313003@zju.edu.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: yecheng liu
  • Chengdu, China
    • Recruiting
    • West China Hospital,Sichuan University
    • Contact: shu zhang
  • Guangdong, China
    • Recruiting
    • Guangdong Provincial People's Hospital
    • Contact: yiyu deng
  • Harbin, China
    • Recruiting
    • The Second Affiliated Hospital of Harbin Medical University
    • Contact: Junbo Zheng
  • Lanxi, China
    • Recruiting
    • Lanxi People's Hospital
    • Contact: jiancheng ducheng
  • Ningbo, China
    • Recruiting
    • Ningbo First Hospital
    • Contact: heng fan
  • Shanghai, China
    • Recruiting
    • Zhognshang hospital, Fudan University
    • Contact: zhenju songzhen
  • Taizhou, China
    • Recruiting
    • Taizhou Hosptial of Zhejiang Province
    • Contact: Sheng Zhang
  • Wuhan, China
    • Recruiting
    • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Contact: yujing zhang
  • Wuhan, China
    • Recruiting
    • Wuhan University Renmin Hospital
    • Contact: Lu Wang
  • Zhengzhou, China
    • Recruiting
    • The First Affiliated Hospital of Zhengzhou University
    • Contact: chao lan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult patients (18 years and older, regardless of gender) admitted to the ICU with ARDS; Intubation and mechanical ventilation; Moderate/severe ARDS defined by Berlin criteria (PaO2/FiO2 ≤200mmHg, PEEP ≥5cmH20); Moderate/severe ARDS less than 48 hours before randomization.

Exclusion Criteria:

Pregnancy or breastfeeding; Known allergy to the intervention drug; Daily use of an intervention drug or measure within the past 15 days; Intervention drugs or measures primarily intended to treat other conditions (eg, septic shock); Patients using the intervention drug or standard for two or more days during hospitalization; Patients are expected to die within the next 24 hours; Other: Participated in PETARDS in the past 90 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: protective ventilation; For ARDS patients with moderate to severe mechanical ventilation(MAQUET), give 6-8ml/kg (ideal body weight PBW), and control the plateau pressure to <30cmH2O; In patients with respiratory distress, the tidal volume can be increased to 7-8ml/kg (PBW), while the plateau pressure is <30cmH2O. Adjust breathing rate according to CO2 level, up to 35 breaths/min. PBW, male: 50+0.91 (height cm-152.4); female: 45.5+0.91 (height cm-152.4).	Device: protective ventilation; Patients with moderate to severe ARDS received ventilation treatment according to predicted body weight(PBW) and controlled plateau pressure.
Experimental: prone position ventilation (including awake state); For patients with moderate to severe ARDS who have no contraindications to prone ventilation, protective lung ventilation is given and prone ventilation is performed; the duration is more than 12 hours/time.	Behavioral: prone position ventilation; patients with moderate to severe ARDS who don't have contraindications were given prone ventilation for over 12 hours.
Experimental: glucocorticoid therapy; Glucocorticoids are used for ARDS patients, with small doses and short courses of treatment in the acute phase (within 14 days). There is no clear recommendation for patients with ARDS from other causes. At present, the main research methods are methylprednisolone program(Solu-Medrol®), dexamethasone program, and hydrocortisone program	Drug: glucocorticoid therapy; Dexamethasone: Patients received intravenous dexamethasone 20 mg daily from days 1 to 5, reduced to 10 mg daily from days 6 to 10. Hydrocortisone：For septic ARDS patients, 50 mg of hydrocortisone was given as an intravenous bolus every 6 hours for 7 days; For patients with COVID-19-related ARDS, The corticosteroid field randomized participants to a fixed 7-day period of intravenous hydrocortisone (50 mg or 100 mg every 6 hours).; Other Names: Dexamethasone; Hydrocortisone
Experimental: restrictive fluid resuscitation; ARDS patients with circulatory or organ hypoperfusion problems should use as little fluid as possible to maintain treatment and circulation; other ARDS patients should focus on stabilizing circulation during the resuscitation phase, with controlled fluid replacement combined with early vasoactive drugs; ultrasound, Central venous pressure measurement, mixed central venous oxygen saturation, alveolar-arterial oxygen difference, blood lactate, etc. guide fluid resuscitation therapy; stop using vasoactive drugs for more than 12 hours, and use diuretics or diuretics combined with albumin to achieve fluid balance.	Other: restrictive fluid resuscitation; without other organ dysfunction patients: Minimize fluid was given;; other ARDS patients: In the resuscitation phase, controlled fluid replacement combined with vasoactive drugs was given; multiple measures were taken, like lactate and so on, to utilizedto guide fluid resuscitation therapy; diuretics or diuretics in combination with albumin to achieve fluid balance.
Experimental: Immunomodulatory therapy; Thymosin Alpha（Thymalfasin for Injection） 1.6mg subcutaneously twice a week.	Biological: Thymosin Alpha; People received thymosin Alpha subcutaneous injections, twice a week.
Experimental: Muscle relaxant therapy; For patients with moderate to severe ARDS, if light sedation cannot achieve protective lung ventilation strategy and prone position ventilation, deep sedation combined with intermittent bolus injection of muscle relaxants（Vecuronium Bromide for Injection） is used; if protective lung ventilation strategy and prone position ventilation still cannot be achieved, deep sedation combined with continuous Inject muscle relaxants.	Drug: Muscle relaxant therapy; Deep sedation combined with intermittent bolus injection of muscle relaxant or deep sedation combined with continuous infusion of muscle relaxant; Other Names: Succinylcholine; Vecuronium Bromide
Experimental: Integrated Chinese and Western Medicine Treatment; Mechanical ventilation + conventional western medicine + Dachengqi Decoction/Rhubarb-Salvia Injection/Tanreqing/Xuanbai Chengqi Decoction(Drugs determined by syndrome differentiation and treatment)	Other: Integrated Chinese and Western Medicine Treatment; ventilation;; conventional western medicine treatment；; Chinese herbal medicine（Determining medication based on syndrome differentiation）
Experimental: statin therapy; There are currently two options: 1) Simvastatin （Simvastatin Tablets）80 mg QD orally for up to 28 days in patients with acute lung injury. 2) Rosuvastatin （Rosuvastatin Calcium Tablets）40 mg for the first time, followed by 20 mg orally daily for 28 days, or 3 days after being transferred out of the ICU, or after the patient died.	Drug: statin therapy; Simvastatin: 80mg qd po for not more than 28days;; Rosuvastatin: 20mg qd po (40mg for the first time) for 28days or 3 days after transfer out of the ICU, or the patient died.; Other Names: Rosuvastatin; Simvastatin
Experimental: anti-infective treatment; Refer to the "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021." recommendations.	Combination product: anti-infective treatment; According to "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".
Experimental: Extracorporeal Membrane Oxygenation（ECMO）; ECMO (Medtronic) is chosen as rescue therapy for severe ARDS patients with refractory hypoxemia within 7 days of onset. (Oxygenation index < 50 mmHg for 3 hours, or oxygenation index < 80 mmHg for 6 hours, or arterial pH < 7.25, arterial partial pressure of carbon dioxide [Paco2] ≥ 60 mmHg > 6 hours, and respiratory rate increased to every minute 35 breaths, adjusting mechanical ventilation settings to maintain plateau pressure ≤32 cmH2O) despite ventilator optimization (defined as inspired oxygen concentration) ≥ 0.80, tidal volume 6 ml/kg (PBW), and positive end-expiratory pressure [PEEP] ≥ 10 cmH2O). V-V mode is preferred.	Device: Extracorporeal Membrane Oxygenation（ECMO）; For severe ARDS patients with refractory hypoxemia within 7 days of onset;; (Inspiratory oxygen concentration) ≥ 0.80, tidal volume 6ml/kg (PBW), positive end-expiratory pressure [PEEP] ≥ 10 cmH2O;; V-V Model.
Experimental: stem cell therapy; Previous clinical studies have found that stem cell therapy is safe, using a single injection of bone marrow stem cells at a dose of 1, 5, 10*106 cells/kg; START trial, ClinicalTrials.gov NCT02097641, for patients with moderate to severe ARDS, a single intravenous injection of bone marrow stem cells 10* 106 cells/kg intervention protocol.	Genetic: stem cell therapy; A single injection of bone marrow stem cells, doses of 1, 5, 10*106 cells/kg was taken according to the previous clinical studies.
Experimental: Sedative analgesia/muscle relaxant therapy; For patients with moderate to severe ARDS, if light sedation cannot achieve protective lung ventilation strategy and prone position ventilation, deep sedation（Propofol Injectable Emulsion or Midazolam Injection） combined with intermittent bolus injection of muscle relaxants is used; if protective lung ventilation strategy and prone position ventilation still cannot be achieved, deep sedation combined with continuous Inject muscle relaxants（Vecuronium Bromide for Injection）.	Drug: Sedative analgesia/muscle relaxant therapy; Deep sedation combined with intermittent bolus injection of muscle relaxant or deep sedation combined with continuous infusion of muscle relaxant; Other Names: midazolam; dexmedetomidine; Propofol
Experimental: inotropes therapy; For unconventional medication, according to"Surviving sepsis campaign: international guidelines for the management of sepsis and septic shock 2021".	Drug: inotropes therapy; According to "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".; Other Names: Dopamine; Olprinone; Levosimendan
Experimental: Vasoactive drug therapy; According to"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".	Drug: Vasoactive drug therapy; According to "Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021".; Other Names: Norepinephrine; epinephrine; metaraminol; isoproterenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ventilator-free days	Ventilator-free days 28 days after randomization, definition: Survival without mechanical ventilation	within 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status assessment	Patients' clinical status (6-point scale score) was assessed on day 15 after randomization, Definition: This scale ranges from 1 (no hospitalization) to 6 (death), with higher scores indicating worse outcomes.	15 days
All-Cause Mortality	All-cause mortality 28 days after randomization	within 28 days
Duration of mechanical ventilation	days of mechanical ventilation	within 28 days
Sequential Organ Failure Assessment (SOFA) Score	SOFA Score for different times, from 0 to 24 points	at 48 hours, 72 hours, and 7 days after randomization
ICU stay time	The time for patients staying in ICU when they were in the hospital.	within 90 days
Hospital stay	The whole time patients lived in the hospital, including the time when they lived in the ICU	within 90 days
Organ failure free days	Patients got ARDS, but the other organs were not injury.	within 28 days
Health-related quality of life assessment, EQ5D-5L and WHODAS 2.0	Patient's life quality was assessed according to EQ5D-5L. If the patient had severe impairment of organ function within 6 months, evaluated the patient's quality of life according to WHODAS 2.0	within 6 months
Proportion of intubated patients undergoing tracheostomy	ARDS patients received tracheostomy.	28 days
Where the patient went after discharge	Home, rehabilitation hospital, nursing home or long-term care facility, or other emergency hospital	No recurrence within 90 days
Re-admission to ICU during readmission	Patients were sent to the hospital and sent to the ICU again,	within 90 days
Days not in intensive care unit	ICU transfer and discharge 28 days after randomization	28 days after randomization

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Fudan University; Peking Union Medical College Hospital; West China Hospital; The First Affiliated Hospital of Zhengzhou University; Guangdong Provincial People's Hospital; Wuhan Union Hospital, China; Renmin Hospital of Wuhan University; The Second Affiliated Hospital of Harbin Medical University; Ningbo No. 1 Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
• Investigators: Study Director: Zhaocai Zhang, Doctor, Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

General Publications

• Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
• Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013 Jun 6;368(23):2159-68. doi: 10.1056/NEJMoa1214103. Epub 2013 May 20.
• Villar J, Ferrando C, Martinez D, Ambros A, Munoz T, Soler JA, Aguilar G, Alba F, Gonzalez-Higueras E, Conesa LA, Martin-Rodriguez C, Diaz-Dominguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Anon JM, Fernandez RL, Gonzalez-Martin JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7.
• Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A; EOLIA Trial Group, REVA, and ECMONet. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018 May 24;378(21):1965-1975. doi: 10.1056/NEJMoa1800385.
• National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF Jr, Hite RD, Harabin AL. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006 Jun 15;354(24):2564-75. doi: 10.1056/NEJMoa062200. Epub 2006 May 21.
• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.
• Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guerin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.
• Annane D, Pastores SM, Rochwerg B, Arlt W, Balk RA, Beishuizen A, Briegel J, Carcillo J, Christ-Crain M, Cooper MS, Marik PE, Umberto Meduri G, Olsen KM, Rodgers S, Russell JA, Van den Berghe G. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med. 2017 Dec;43(12):1751-1763. doi: 10.1007/s00134-017-4919-5. Epub 2017 Sep 21. Erratum In: Intensive Care Med. 2018 Feb 23;:
• Meduri GU, Annane D, Confalonieri M, Chrousos GP, Rochwerg B, Busby A, Ruaro B, Meibohm B. Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS. Intensive Care Med. 2020 Dec;46(12):2284-2296. doi: 10.1007/s00134-020-06289-8. Epub 2020 Nov 4.
• Vignon P, Evrard B, Asfar P, Busana M, Calfee CS, Coppola S, Demiselle J, Geri G, Jozwiak M, Martin GS, Gattinoni L, Chiumello D. Fluid administration and monitoring in ARDS: which management? Intensive Care Med. 2020 Dec;46(12):2252-2264. doi: 10.1007/s00134-020-06310-0. Epub 2020 Nov 9.
• Malbrain MLNG, Van Regenmortel N, Saugel B, De Tavernier B, Van Gaal PJ, Joannes-Boyau O, Teboul JL, Rice TW, Mythen M, Monnet X. Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy. Ann Intensive Care. 2018 May 22;8(1):66. doi: 10.1186/s13613-018-0402-x.
• Alhazzani W, Belley-Cote E, Moller MH, Angus DC, Papazian L, Arabi YM, Citerio G, Connolly B, Denehy L, Fox-Robichaud A, Hough CL, Laake JH, Machado FR, Ostermann M, Piraino T, Sharif S, Szczeklik W, Young PJ, Gouskos A, Kiedrowski K, Burns KEA. Neuromuscular blockade in patients with ARDS: a rapid practice guideline. Intensive Care Med. 2020 Nov;46(11):1977-1986. doi: 10.1007/s00134-020-06227-8. Epub 2020 Oct 26.
• McAuley DF, Laffey JG, O'Kane CM, Cross M, Perkins GD, Murphy L, McNally C, Crealey G, Stevenson M; HARP-2 investigators; Irish Critical Care Trials Group. Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial. Trials. 2012 Sep 17;13:170. doi: 10.1186/1745-6215-13-170.
• McAuley 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. Erratum In: N Engl J Med. 2016 Nov 17;375(20):2010.
• National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.
• Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011 Nov 17;365(20):1905-14. doi: 10.1056/NEJMct1103720.
• Qin H, Zhao A. Mesenchymal stem cell therapy for acute respiratory distress syndrome: from basic to clinics. Protein Cell. 2020 Oct;11(10):707-722. doi: 10.1007/s13238-020-00738-2. Epub 2020 Jun 9.
• Matthay MA, Calfee CS, Zhuo H, Thompson BT, Wilson JG, Levitt JE, Rogers AJ, Gotts JE, Wiener-Kronish JP, Bajwa EK, Donahoe MP, McVerry BJ, Ortiz LA, Exline M, Christman JW, Abbott J, Delucchi KL, Caballero L, McMillan M, McKenna DH, Liu KD. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med. 2019 Feb;7(2):154-162. doi: 10.1016/S2213-2600(18)30418-1. Epub 2018 Nov 16.
• Wick KD, Leligdowicz A, Zhuo H, Ware LB, Matthay MA. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight. 2021 Jun 22;6(12):e148983. doi: 10.1172/jci.insight.148983.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: ICU; ARDS; domain; platform adaptive embedded trial
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antimetabolites; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Neuromuscular Agents; Phosphodiesterase Inhibitors; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nicotinic Antagonists; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Phosphodiesterase 3 Inhibitors; Adrenergic alpha-1 Receptor Agonists; Neuromuscular Depolarizing Agents; Dexamethasone; Midazolam; Propofol; Dexmedetomidine; Rosuvastatin Calcium; Norepinephrine; Anti-Infective Agents; Simvastatin; Bromides; Epinephrine; Hydrocortisone; Simendan; Dopamine; Hypnotics and Sedatives; Succinylcholine; Glucocorticoids; Metaraminol; Vecuronium Bromide; Isoproterenol; Olprinone
• Other Study ID Numbers: 2022-0770

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all collected IPD；; all IPD that underlie results in a publication.
• IPD Sharing Time Frame: Data will be permanently available after the publication of this study.
• IPD Sharing Access Criteria: Data will be made available to all upon publication of this study. Applicants can contact the corresponding author to apply, but they must provide the reasons for the application, the purpose of the research, and the ethical certificates of the relevant research.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No