Trial record 2 of 8 for:    inhaled treprostinil sodium | Open Studies

Treprostinil Sodium Inhalation for Patients At High Risk for ARDS

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
H. James Ford, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02370095
First received: January 30, 2015
Last updated: April 11, 2016
Last verified: April 2016
  Purpose
Acute Respiratory Distress Syndrome (ARDS) is a rapidly progressing lung disease caused by a number of factors including pneumonia, sepsis and acute trauma that leads to reduced lung function and breathlessness. There are no pharmacological treatments approved for the treatment of ARDS. This pilot trial will study the safety and efficacy of Treprostinil sodium by inhalation for preventing the progression of acute hypoxemic respiratory failure to positive pressure ventilation and/or ARDS in patients at high risk.

Condition Intervention Phase
Respiratory Distress Syndrome, Adult
Drug: Treprostinil Inhalation Solution
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Treprostinil Sodium Inhalation for Patients At High Risk for ARDS: Effect on Oxygenation and Disease-related Biomarkers

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Change in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2 ratio) from day 0 to days 2 and 7 [ Time Frame: Change in PaO2/FiO2 ratio from day 0 to 2, 7 and 28 (if subject still hospitalized) ]
    Ratio of the arterial oxygen partial pressure divided by the fraction of inspired oxygen


Secondary Outcome Measures:
  • Number of ventilator-free days to day 28 [ Time Frame: 0-28 days post enrollment ]
  • Number of subjects who required Bi-level Positive Airway Pressure (BiPAP) or Continuous Positive Airway Pressure (CPAP) via face mask from Day 0 to Day 28 [ Time Frame: 0-28 days ]
  • Change in the ratio of peripheral oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) from day 0 to day 12 [ Time Frame: 0-12 days ]
    Ratio of oxygen saturation divided by the fraction of inspired oxygen

  • Change in ARDS associated plasma biomarkers from day 0 to day 3 and day 7 [ Time Frame: Change from day 0 on days 3 and 7 ]
  • Change in the central venous oxygen saturation (SCVO2) from day 0 to day 3 [ Time Frame: Change in SCVO2 from Day 0 to 3 (if central venous catheter in place) ]
    central venous oxygen saturation only measured if a central venous catheter is in place

  • Change in central venous pressure (CVP) from day 0 to day 3 [ Time Frame: Change in CVP from Day 0 to 3 (if central venous catheter in place) ]
    Central Venous Pressure only measured if a central venous catheter is in place

  • Change in mean arterial pressure (MAP) from day 0 to day 7 [ Time Frame: Change in MAP and from an arterial line (if placed) or cuff from Day 0 to day 7 ]
    mean arterial pressure calculated from an arterial line or blood pressure cuff

  • All-cause mortality from day 0 to day 28 for each treatment arm [ Time Frame: 0-28 days ]
    Death

  • Proportion of subjects requiring intubation and mechanical ventilation from day 0 to day 28 [ Time Frame: 0-28 days ]
    Number of subjects requiring intubation and mechanical ventilation per treatment arm

  • Hospital Mortality up to 3 months [ Time Frame: Entire Duration of Hospitalization expected to range from 1 week to 3 months ]
  • Individual plasma peak and trough treprostinil concentration [ Time Frame: Day 3 ]
    Peak plasma concentration determined 15 min after inhalation and trough determined 4 hours following the drug/placebo administration

  • Time to intubation and mechanical ventilation from day 0 to day 28 [ Time Frame: Day 0 to day 28 ]

Estimated Enrollment: 30
Study Start Date: February 2015
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treprostinil inhalation solution
Treprostinil will be randomized 2:1 to placebo. Treprostinil (6 mcg per breath) will be administered every 4 hours. The dose will increase from 6 to12 breaths (maximum 72 mcg) over the first 20 hours, maintained for 7 days, and tapered down over 3 days.
Drug: Treprostinil Inhalation Solution
Treprostinil inhalation solution administered as blinded marketed product
Other Name: TYVASO
Placebo Comparator: Placebo
Placebo administration will be administered as above for the active arm
Drug: Placebo
Supplied by the manufacturer and similar to the active drug but containing no Treprostinil
Other Name: Sterile saline solution

Detailed Description:

ARDS is defined by acute hypoxemia, respiratory failure and the presence of bilateral lung infiltrates. ARDS is a syndrome of inflammation and increased permeability that may coexist with left atrial or pulmonary capillary hypertension. Several recent trials in ARDS/ALI (Acute Lung Injury) have generated interest in the use of Prostacyclin (PGI2) and prostacyclin analogs in improving oxygenation in ARDS/ALI. PGI2 is an arachidonic acid metabolite naturally produced in the lung by endothelial cells, dendritic cells, smooth muscle cells and fibroblasts. PGI2 is a potent selective pulmonary vasodilator and inhibitor of platelet aggregation. The cellular effects include smooth muscle relaxation, inhibition of cell migration, decreased dextran permeability in epithelial cell cultures in vitro, decreased high tidal volume mechanical ventilation injury in mice and inhibition of fibroblast adhesion and differentiation. PGI2 has broad anti-inflammatory activity, inhibiting the production of Tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and granulocyte macrophage colony-stimulating factor (GMCSF) in human alveolar macrophages.

The study objectives are:

  1. To assess the feasibility of a randomized trial of treprostinil inhalation in patients with acute hypoxemic respiratory failure not requiring positive pressure ventilation.
  2. To evaluate the tolerability of inhaled treprostinil for patients with acute hypoxemic respiratory failure
  3. To assess the effect of treprostinil inhalation on oxygenation in patients with acute hypoxic respiratory failure with, or at risk for, development of ARDS
  4. To assess the effect of treprostinil inhalation on various biomarkers thought to be related to the pathogenesis and/or clinical course of ARDS.

The hypothesis is: Treprostinil solution for inhalation (TYVASO) is safe and will improve oxygenation and other secondary outcomes related to acute hypoxemic respiratory failure and positive pressure ventilation initiation and duration, as well as exhibit effects on ARDS-related pro-inflammatory and pro-fibrotic biomarkers.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults age 18-75 years.
  2. Acute onset need for 4 liters per minute (LPM) or more of supplemental oxygen to maintain PaO2 > 60 mmHg or arterial O2 saturation > 90% by pulse oximetry.
  3. Acute unilateral pulmonary infiltrate/s on chest radiograph with no clinical evidence of left-sided heart failure. Bilateral infiltrates are acceptable as long as all other inclusion/exclusion criteria are met.

Exclusion Criteria:

  1. No consent/inability to obtain consent
  2. Presence of pulmonary embolism
  3. Known diffuse alveolar hemorrhage from vasculitis
  4. Known pre-existing severe obstructive or restrictive lung disease (FEV 1 < 40% predicted, total lung capacity (TLC) < 50 % predicted) or need for long-term supplemental oxygen therapy
  5. Known significant left ventricular systolic dysfunction with left ventricular ejection fraction (LVEF) < 45% on echocardiogram.
  6. Mean arterial pressure < 65 mmHg
  7. Need for norepinephrine or dopamine dose > 12 mcg to maintain MAP > 65 mmHg
  8. Severe chronic liver disease (Child-Pugh Score 11-15)
  9. Moribund patient not expected to survive 24 hours
  10. Corrected QT interval (QTc) interval > 500 ms on screening electrocardiogram
  11. Pregnancy or breast feeding (Women of childbearing potential, defined as < 60 years of age, will require pregnancy testing.)
  12. Burns > 40% total body surface
  13. Acute Neurological Disease (that may impair the ability to ventilate without assistance)
  14. Imminent need for intubation or non-invasive ventilation
  15. Patient is Do Not Resuscitate/Do Not Intubate
  16. Patient has a tracheotomy
  17. Patient is currently receiving prostacyclin therapy [Epoprostenol (Flolan or Veltri), Iloprost (Ventavis), Treprostinil (Orenitram, oral) (Remodulin, IV or SC)]
  18. Patient has a language barrier
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02370095

Contacts
Contact: Hubert J Ford, MD 919 966-2531 hubert_ford@med.unc.edu
Contact: Joyce Lanier, RRT 966-2531 joyce_lanier@med.unc.edu

Locations
United States, North Carolina
University of North Carolina Hospitals Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: James Ford, MD    919-966-2531    hubert_ford@med.unc.edu   
Contact: Joyce Lanier, RRT    9199662531    joyce_lanier@med.unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
United Therapeutics
Investigators
Principal Investigator: Hubert J Ford, MD University of North Carolina, Chapel Hill
Principal Investigator: Shannon Carson, MD University of North Carolina, Chapel Hill
Principal Investigator: Wayne H Anderson, PhD University of North Carolina, Chapel Hill
  More Information

Publications:

Responsible Party: H. James Ford, MD, Clinical Assistant Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02370095     History of Changes
Other Study ID Numbers: 14-0490 
Study First Received: January 30, 2015
Last Updated: April 11, 2016

Keywords provided by University of North Carolina, Chapel Hill:
ARDS
Acute Lung Injury
Acute Respiratory Failure

Additional relevant MeSH terms:
Treprostinil
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Pharmaceutical Solutions
Antihypertensive Agents

ClinicalTrials.gov processed this record on January 23, 2017