Treprostinil Sodium Inhalation for Patients At High Risk for ARDS

NCT02370095 | Terminated Phase 2 Results DMC

• 1 other identifier: 14-0490
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Respiratory Distress Syndrome, Adult

Keywords

ARDS; Acute Lung Injury; Acute Respiratory Failure

Outcome Measures

Primary Outcomes (1)

• Change in the Ratio of the Partial Pressure of Arterial Oxygen to the Fraction of Inspired Oxygen (PaO2/FiO2 Ratio)

  PaO2/FiO2 ratio

  Change in PaO2/FiO2 ratio from day 0 to day 2.

Secondary Outcomes (12)

• Change in the Ratio of Peripheral Oxygen Saturation to Fraction of Inspired Oxygen (SaO2/FiO2)

  0-12 days

• Number of Days Not on a Ventilator

  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

  0-28 days

• Acute Respiratory Distress Syndrome (ARDS) Associated Biomarkers

  Change from day 0 on days 3 and 7

• Change in the Central Venous Oxygen Saturation (SCVO2).

  Change in SCVO2 from Day 0 to 3 (if central venous catheter in place)

Study Arms (2)

Treprostinil inhalation solution

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Placebo administration will be administered as above for the active arm

Drug: Placebo

Interventions

Treprostinil Inhalation Solution DRUG

Treprostinil inhalation solution administered as blinded marketed product

Also known as: TYVASO

Treprostinil inhalation solution

Placebo DRUG

Supplied by the manufacturer and similar to the active drug but containing no Treprostinil

Also known as: Sterile saline solution

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults age 18-75 years.
• Acute onset need for 4 liters per minute (LPM) or more of supplemental oxygen to maintain Arterial partial pressure of oxygen (PaO2) \> 60 mmHg or arterial O2 saturation \> 90% by pulse oximetry.

You may not qualify if:

• No consent/inability to obtain consent
• Presence of pulmonary embolism
• Known diffuse alveolar hemorrhage from vasculitis
• 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
• Known significant left ventricular systolic dysfunction with left ventricular ejection fraction (LVEF) \< 45% on echocardiogram.
• Mean arterial pressure \< 65 mmHg
• Need for norepinephrine or dopamine dose \> 12 mcg to maintain mean arterial pressure (MAP) \> 65 mmHg
• Severe chronic liver disease (Child-Pugh Score 11-15)
• Moribund patient not expected to survive 24 hours
• Corrected QT interval (QTc) interval \> 500 ms on screening electrocardiogram
• Pregnancy or breast feeding (Women of childbearing potential, defined as \< 60 years of age, will require pregnancy testing.)
• Burns \> 40% total body surface
• Acute Neurological Disease (that may impair the ability to ventilate without assistance)
• Imminent need for intubation or non-invasive ventilation
• Patient is Do Not Resuscitate/Do Not Intubate

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• United Therapeutics: collaborator

Study Sites (1)

University of North Carolina Hospitals

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (8)

• Zwissler B, Kemming G, Habler O, Kleen M, Merkel M, Haller M, Briegel J, Welte M, Peter K. Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1671-7. doi: 10.1164/ajrccm.154.6.8970353.

  PMID: 8970353 BACKGROUND

• Walmrath D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W. Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am J Respir Crit Care Med. 1996 Mar;153(3):991-6. doi: 10.1164/ajrccm.153.3.8630585.

  PMID: 8630585 BACKGROUND

• Walmrath D, Schneider T, Pilch J, Schermuly R, Grimminger F, Seeger W. Effects of aerosolized prostacyclin in severe pneumonia. Impact of fibrosis. Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 1):724-30. doi: 10.1164/ajrccm.151.3.7881662.

  PMID: 7881662 BACKGROUND

• Domenighetti G, Stricker H, Waldispuehl B. Nebulized prostacyclin (PGI2) in acute respiratory distress syndrome: impact of primary (pulmonary injury) and secondary (extrapulmonary injury) disease on gas exchange response. Crit Care Med. 2001 Jan;29(1):57-62. doi: 10.1097/00003246-200101000-00015.

  PMID: 11176161 BACKGROUND

• Dahlem P, van Aalderen WM, de Neef M, Dijkgraaf MG, Bos AP. Randomized controlled trial of aerosolized prostacyclin therapy in children with acute lung injury. Crit Care Med. 2004 Apr;32(4):1055-60. doi: 10.1097/01.ccm.0000120055.52377.bf.

  PMID: 15071401 BACKGROUND

• Dorris SL, Peebles RS Jr. PGI2 as a regulator of inflammatory diseases. Mediators Inflamm. 2012;2012:926968. doi: 10.1155/2012/926968. Epub 2012 Jul 18.

  PMID: 22851816 BACKGROUND

• Raychaudhuri B, Malur A, Bonfield TL, Abraham S, Schilz RJ, Farver CF, Kavuru MS, Arroliga AC, Thomassen MJ. The prostacyclin analogue treprostinil blocks NFkappaB nuclear translocation in human alveolar macrophages. J Biol Chem. 2002 Sep 6;277(36):33344-8. doi: 10.1074/jbc.M203567200. Epub 2002 Jun 24.

  PMID: 12082102 BACKGROUND

• Ford HJ, Anderson WH, Wendlandt B, Bice T, Ceppe A, Lanier J, Carson SS. Randomized, Placebo-controlled Trial of Inhaled Treprostinil for Patients at Risk for Acute Respiratory Distress Syndrome. Ann Am Thorac Soc. 2021 Apr;18(4):641-647. doi: 10.1513/AnnalsATS.202004-374OC.

  PMID: 33095030 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Acute Lung Injury

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury

Limitations and Caveats

The study was stopped because of low recruitment. The limited number of subjects make it difficult to draw conclusions regarding the efficacy of Treprostinil in subjects at high risk of developing ARDS.

Results Point of Contact

• Title: Wayne H Anderson, PhD
• Organization: University of North Carolina at Chapel Hill

wayne_anderson@med.unc.edu

919-445-0351

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2015
• First Posted: February 24, 2015
• Study Start: February 1, 2015
• Primary Completion: October 11, 2017
• Study Completion: November 7, 2017
• Last Updated: October 1, 2019
• Results First Posted: October 1, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)