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Trial record 6 of 203 for:    Recruiting, Not yet recruiting, Available Studies | Neonatal respiratory distress syndrome

Mesenchymal Stromal Cells For Acute Respiratory Distress Syndrome (STAT)

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ClinicalTrials.gov Identifier: NCT03818854
Recruitment Status : Not yet recruiting
First Posted : January 28, 2019
Last Update Posted : November 14, 2019
Sponsor:
Collaborators:
United States Department of Defense
Harborview Injury Prevention and Research Center
Oregon Health and Science University
Vanderbilt University Medical Center
The University of Texas Health Science Center, Houston
University of Minnesota
Information provided by (Responsible Party):
Michael A. Matthay, University of California, San Francisco

Brief Summary:
This is a Phase 2b, randomized, double-blind, placebo-controlled, multi-center study to assess the safety and efficacy of a single dose of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) infusion in patients with Acute Respiratory Distress Syndrome (ARDS). This study is the extension of the Phase 1 pilot study (NCT01775774) and Phase 2a study (NCT02097641).

Condition or disease Intervention/treatment Phase
Respiratory Distress Syndrome, Adult Biological: Human Mesenchymal Stromal Cells Biological: Cell Reconstitution Media Phase 2

Detailed Description:

This clinical study design is a randomized, double-blinded, placebo-controlled Phase 2b clinical trial using a 10 million cell/kg dose of human Mesenchymal Stromal Cells (hMSCs). Subjects will be randomized in a 1:1 randomization scheme to receive hMSCs or cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) as the placebo; the study will enroll 120 patients who achieve a stable clinical baseline and receive study product (either hMSCs or the placebo).

The Data and Safety Monitoring Board (DSMB) will review adverse outcomes and protocol compliance. A pre-specified interim review will occur after 60 subjects have been enrolled and received study product; enrollment will continue during the DSMB review. All pre-specified clinically important events and unexpected serious adverse events including death during hospitalization up to 60 days will be reported to the DSMB on an ongoing basis; the study will be stopped for a safety evaluation by the DSMB if they have any concerns or if three subjects have pre-specified clinically important events or unexpected serious adverse events except death since death will be common in this critically ill population due the nature of the underlying illness (e.g., ARDS).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: For this Phase 2b trial, after informed consent is given, an assignment will be made by computer-generated randomization to administer either hMSCs therapy or placebo with a 1:1 allocation to the hMSCs:placebo arms.
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Trial of Allogeneic Bone Marrow-derived Human Mesenchymal Stromal Cells (hMSCs) for the Treatment of Acute Respiratory Distress Syndrome
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : July 1, 2024


Arm Intervention/treatment
Experimental: Human Mesenchymal Stromal Cells
A single dose of 10 million cells/kg predicted body weight (PBW) Allogeneic Bone Marrow-Derived Human Mesenchymal Stromal Cells will administered intravenously over approximately 60-80 minutes.
Biological: Human Mesenchymal Stromal Cells
Immediately prior to administration, the study product will be thawed and diluted 1:1 with reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40). Additional reconstitution media is added to a final product volume of 300 mL.
Other Name: hMSCs

Experimental: Cell Reconstitution Media
A single dose of cell reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40) will administered intravenously over approximately 60-80 minutes.
Biological: Cell Reconstitution Media
300 mL of reconstitution media (1:1 mix of 5% human serum albumin and 10% Dextran 40)
Other Name: Placebo




Primary Outcome Measures :
  1. Change in oxygenation index (OI) [ Time Frame: 36 hours ]
    Change in OI from baseline over the 36 hours following the infusion of study product


Secondary Outcome Measures :
  1. Acute Lung Injury Score (LIS) [ Time Frame: 7 days ]
    LIS over 7 days, or on the last day of positive pressure ventilation prior to day 7. The LIS is a composite 4-point scoring system including the PaO2/FiO2, PEEP, lung compliance, and the extent of infiltrates on the chest X-ray. Each of the four components is categorized from 0 to 4, where a higher number is worse. The total Lung Injury Score is obtained by dividing the aggregate sum by the number of components used.

  2. Pulmonary Dead Space Fraction [ Time Frame: 7 days ]
    Pulmonary Dead Space at day 1, 2, 3 and 7. The dead-space fraction is calculated as: (PaCO2 - PeCO2) ÷ PaCO2

  3. Chest radiograph assessment of pulmonary edema (RALE score) [ Time Frame: 7 days ]
    RALE score at day 1, 2, 3 and 7. To calculate RALE, each radiographic quadrant is scored for extent of consolidation (0-4) and density of opacification (1-3). The product of the consolidation and density scores for each of the four quadrants is summed. The RALE score ranges from 0 (best) to 48 (worst).

  4. Ventilator free-days [ Time Frame: 28 days ]
    Ventilator free-days over 7, 14 and 28 days

  5. Duration of assisted ventilation over 28 days [ Time Frame: 28 days ]
    Duration of assisted ventilation over 28 days in the survivors

  6. Percentage of patients achieving pressure support ventilation for 2 hours [ Time Frame: 28 days ]
    Percentage of patients achieving pressure support ventilation equal to 5 cm H2O with positive end-expiratory pressure (PEEP) equal to 5 cm H2O for 2 hours

  7. Occurrence of Infection [ Time Frame: 14 days ]
    Superficial incisional/wound infections, deep incisional wound infections, and organ/space infections, and ventilator associated pneumonia (all during the 14 days after enrollment)

  8. Sequential Organ Failure Assessment (SOFA) [ Time Frame: 14 days ]
    SOFA score at 3, 7 and 14 days. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems which are added up. Each score ranges from 0 to 4. SOFA score ranges from 0 (best) to 24 (worst).

  9. All-cause hospital mortality [ Time Frame: 60 days ]
    All-cause hospital mortality at 14, 28 and 60 days

  10. Glasgow Outcome Score (GCS) [ Time Frame: 60 days ]
    Glasgow Outcome Score at hospital discharge. The GCS is a scale to evaluate level of consciousness in patients with acute brain injury. The scale assesses 3 functions: Eye Opening, Verbal Response, and Motor Response. GCS scores range from 15 (best) to 3 (worst)

  11. Percentage of patients occurred any thromboembolic events [ Time Frame: 60 days ]
    Thromboembolic events are measured by ultrasound of the deep venous system or CT-angiography of the chest ordered for clinical purposes/by treating clinicians

  12. Plasma angiopoietin-2 [ Time Frame: 72 hours ]
    Change in levels of plasma angiopoietin-2 from baseline compared to 6, 24, 48 and 72 hours

  13. Plasma Receptor for Advanced Glycation Endproducts (RAGE) [ Time Frame: 72 hours ]
    Change in levels of plasma RAGE from baseline compared to 6, 24, 48 and 72 hours

  14. Plasma interleukin-6 [ Time Frame: 72 hours ]
    Change in levels of plasma interleukin-6 from baseline compared to 6, 24, 48 and 72 hours

  15. Plasma interleukin-8 [ Time Frame: 72 hours ]
    Change in levels of plasma interleukin-8 from baseline compared to 6, 24, 48 and 72 hours

  16. Plasma Soluble tumor necrosis factor 1 (sTNF-1) [ Time Frame: 72 hours ]
    Change in levels of plasma sTNF-1 from baseline compared to 6, 24, 48 and 72 hours

  17. Plasma protein C [ Time Frame: 72 hours ]
    Change in levels of plasma protein C from baseline compared to 6, 24, 48 and 72 hours

  18. Plasma lipoxin A4 [ Time Frame: 72 hours ]
    Change in levels of plasma lipoxin A4 from baseline compared to 6, 24, 48 and 72 hours

  19. Plasma Resolvin D1 [ Time Frame: 72 hours ]
    Change in levels of plasma Resolvin D1 from baseline compared to 6, 24, 48 and 72 hours

  20. Plasma angiopoietin-1 [ Time Frame: 72 hours ]
    Change in levels of plasma angiopoietin-1 from baseline compared to 6, 24, 48 and 72 hours

  21. Plasma keratinocyte growth factor (KGF) [ Time Frame: 72 hours ]
    Change in levels of plasma KGF from baseline compared to 6, 24, 48 and 72 hours

  22. Urine interleukin-6 [ Time Frame: 72 hours ]
    Change in levels of urine interleukin-6 from baseline compared to 6, 24, 48 and 72 hours

  23. Urine microalbumin [ Time Frame: 72 hours ]
    Change in levels of urine microalbumin from baseline compared to 6, 24, 48 and 72 hours

  24. Total protein in min-bronchoalveolar lavage (mBAL) [ Time Frame: 2 days ]
    Change in total protein levels in from baseline to day 2

  25. Tolerability of the hMSCs - incidence of pre-specified infusion-associated events and unexpected severe adverse events [ Time Frame: 24 hours ]
    Tolerability of the hMSCs, defined as the incidence of pre-specified infusion-associated events and unexpected severe adverse events in ARDS patients treated with human MSCs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients will be eligible for inclusion if they meet all of the below criteria within 120 hours of initial ICU admission. Criteria 1-3 must all be present within a 24-hour time period and at the time of enrollment:

Acute onset (defined below) of:

  1. A need for positive pressure ventilation by an endotracheal or tracheal tube with a PaO2/FiO2 ratio <200 mmHg and ≥5 cm H2O positive end-expiratory airway pressure (PEEP), as per the Berlin Criteria.
  2. Bilateral infiltrates consistent with pulmonary edema (defined below) on the frontal chest radiograph, or bilateral ground glass opacities on a chest CT scan.
  3. No clinical evidence of left atrial hypertension as a primary explanation for the bilateral pulmonary infiltrates.
  4. If the cause of ARDS is trauma, additional inclusion criteria will include ONE of the following relevant risk factors for developing ARDS:

    1. Hypotension (systolic blood pressure[SBP] < 90 mmHg) in the field or in the first 24 h after injury, or
    2. Transfusion of 3 units of blood products in the first 24 hours following injury, or
    3. Meets the new Critical Administration Threshold (CAT) criteria with at least 3 units of blood in one hour, or
    4. Blunt or penetrating torso trauma, or
    5. Long bone fractures, or
    6. The highest level of institutional trauma activation

Exclusion Criteria:

  1. Age less than 18 years
  2. Greater than 72 hours since first meeting ARDS criteria per the Berlin definition of ARDS
  3. Greater than 120 hours since initial ICU admission
  4. Inability to administer study product within 120 hours of ICU admission
  5. PaO2/FiO2 ≥ 200 mmHg after consent obtained and before study product is administered
  6. Unable to obtain informed consent/no surrogate available
  7. Pregnant or lactating
  8. In custody of law enforcement officials
  9. Burns > 20% of total body surface area
  10. WHO Class III or IV pulmonary hypertension
  11. History of cancer treatment in the last 2 years except for non-melanotic skin cancers
  12. Underlying medical condition for which 6-month mortality is estimated to be > 50%
  13. Moribund patient not expected to survive 24 hours
  14. Advanced chronic liver disease (Childs-Pugh Score > 12)
  15. Severe chronic respiratory disease with the use of home oxygen
  16. Severe traumatic brain injury - defined as:

    1. A patient who has undergone intracranial neurosurgical intervention for monitoring or therapy (intracranial pressure monitoring, external ventricular drain, craniotomy), or
    2. Intracranial injury by head CT (does not include patients with minimal subarachnoid injury and/or minor skull fracture), or
    3. Post-resuscitation Glasgow Coma Score (GCS) < 9 assessed after sedation interruption, or
    4. Non-survivable head injury as assessed by neurosurgery
  17. Evidence of anoxic brain injury
  18. History of stroke within the last 3 years
  19. No intent/unwillingness to follow lung protective ventilation strategy
  20. Currently receiving extracorporeal life support (ECLS) or high-frequency oscillatory ventilation (HFOV)
  21. Anticipated extubation within 24 hours of enrollment
  22. Clinical evidence of left atrial hypertension as measured by a pulmonary arterial wedge pressure > 18mmHg or left ventricular failure measured by an echocardiogram with a left ventricular ejection fraction less than 40%. Clinical judgement will determine if either of these measurements needs to be carried out.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03818854


Contacts
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Contact: Michael Matthay, MD 415-502-7434 ext 4155027434 michael.matthay@ucsf.edu
Contact: Hanjing Zhuo, MPH 415-502-7434 hanjing.zhuo@ucsf.edu

Locations
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United States, California
Zuckerberg San Francisco General Hospital and Trauma Center Not yet recruiting
San Francisco, California, United States, 94110
Contact: Rachael A Callcut, MD, MSPH    415-206-4623    CallcutR@sfghsurg.ucsf.edu   
Principal Investigator: Rachael Callcut, MD, MSPH         
Sub-Investigator: Carolyn M Hendrickson, MD, MPH         
Sub-Investigator: Lucy Kornblith, MD         
University of California San Francisco Not yet recruiting
San Francisco, California, United States, 94143
Contact: Michael Matthay, MD    415-502-7434    michael.matthay@ucsf.edu   
Contact: Hanjing Zhuo, MPH    415-502-7434    hanjing.zhuo@ucsf.edu   
Principal Investigator: Michael A Matthay, MD         
Sub-Investigator: Carolyn S Calfee, MD, MD, MAS         
Sub-Investigator: Kathleen D Liu, MD, PhD, MAS         
Sub-Investigator: Jeffrey E Gotts, MD, PhD         
United States, Oregon
Oregon Health & Science University Not yet recruiting
Portland, Oregon, United States, 97239
Contact: Martin A Schreiber, MD, FACS    503-494-6518    schreibm@ohsu.edu   
Principal Investigator: Martin Schreiber, MD         
Sub-Investigator: Akram Khan, MD         
Sub-Investigator: David Zonies, MD         
United States, Tennessee
Vanderbilt University Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Lorraine B Ware, MD    615-322-7872    lorraine.ware@Vanderbilt.edu   
Principal Investigator: Lorraine B Ware, MD         
Sub-Investigator: Oscar Guillamondegui, MD         
United States, Texas
Memorial Hermann Hospital - Texas Medical Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Laura H Moore, MD, FACS    713-500-7217    laura.j.moore@uth.tmc.edu   
Principal Investigator: Laura H Moore, MD         
Sub-Investigator: Charles E Wade, PhD         
Sub-Investigator: John Holcomb, MD         
Sub-Investigator: Charles Cox, MD         
Sub-Investigator: Erin Fox, MD         
Sub-Investigator: Lillian Kao, MD         
United States, Washington
Harborview Medical Center Not yet recruiting
Seattle, Washington, United States, 98112
Contact: Bryce RH Robinson, MD, MS    206-482-2277    brobinso@uw.edu   
Principal Investigator: Bryce Robinson, MD         
Sub-Investigator: Terri Hough, MD         
Sub-Investigator: Joseph Cuschieri, MD         
Sponsors and Collaborators
Michael A. Matthay
United States Department of Defense
Harborview Injury Prevention and Research Center
Oregon Health and Science University
Vanderbilt University Medical Center
The University of Texas Health Science Center, Houston
University of Minnesota
Investigators
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Principal Investigator: Michael Matthay, MD University of California, San Francisco

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Responsible Party: Michael A. Matthay, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03818854     History of Changes
Other Study ID Numbers: UCSF-hMSC-ARDS-P1P2-09
First Posted: January 28, 2019    Key Record Dates
Last Update Posted: November 14, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We do not have plan to share IPD data to other researchers.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael A. Matthay, University of California, San Francisco:
Human Mesenchymal Stromal Cells
Acute Respiratory Distress Syndrome
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Syndrome
Respiratory Tract Diseases
Infant, Newborn, Diseases
Acute Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiration Disorders
Infant, Premature, Diseases
Lung Injury
Dextrans
Anticoagulants
Plasma Substitutes
Blood Substitutes