Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (PAH) (TRIUMPH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00147199
Recruitment Status : Completed
First Posted : September 7, 2005
Results First Posted : August 12, 2013
Last Update Posted : August 12, 2013
Information provided by (Responsible Party):
United Therapeutics

Brief Summary:
This is a double-blind placebo-controlled clinical investigation into the efficacy and tolerability of inhaled treprostinil in patients with severe pulmonary arterial hypertension. The primary outcome is the change in 6-minute walk distance from baseline to week 12.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: Inhaled treprostinil Drug: Placebo inhalation solution Phase 3

Detailed Description:

Patients who have been on a stable dose of 125 mg twice daily (bid) of bosentan or any stable dose of sildenafil for at least three months prior to study start were randomized to either treprostinil inhalation solution or matching placebo.

Administration of study medication was performed by inhalation with the OPTINEB™ ultrasonic nebulizer.

The proposed dosing regimen was four times daily—upon awakening, at midday, evening (dinner time) and bedtime.

After a patient has completed the twelve-week study period, they were given the option of enrolling into an open-label extension study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 235 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: TRIUMPH I: Double Blind Placebo Controlled Clinical Investigation Into the Efficacy and Tolerability of Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension
Study Start Date : June 2005
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Arm Intervention/treatment
Experimental: Inhaled treprostinil
0.9 mg/mL treprostinil for inhalation supplied in 2.9mL ampoules for use in ultra sonic nebulizer
Drug: Inhaled treprostinil
Doses are titrated to 9 breaths four times daily. Each breath produces an 18 mcg dose of inhaled treprostinil.
Other Name: Tyvaso
Placebo Comparator: Placebo
Placebo inhalation solution for use in ultrasonic nebulizer
Drug: Placebo inhalation solution
Doses are titrated to 9 breaths four times daily.
Other Name: Placebo

Primary Outcome Measures :
  1. Peak 6-minute Walk Distance [ Time Frame: 12 weeks ]
    Change in peak 6-minute walk distance from baseline to Week 12. Peak 6MWD was defined as a 6-minute walk test (6MWT) within 10 to 60 minutes after study drug inhalation

Secondary Outcome Measures :
  1. Clinical Worsening Events [ Time Frame: 12 weeks ]
    Clinical worsening was defined as the first incidence of clinical worsening from randomization to the first occurrence of death, transplantation, hospitalization for PAH, or initiation of additional approved PAH therapy.

  2. Borg Dyspnea Score [ Time Frame: 12 weeks ]
    The Borg dyspnea score is a patient reported number between 0 (no perceived shortness of breath) and 10 (maximum perceived shortness of breath), obtained at the completion of each 6MWT.

  3. New York Heart Association (NYHA) Functional Classification [ Time Frame: 12 weeks ]

    Change in NYHA functional class at Week 12. NYHA classifications:

    Class I - Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope.

    Class II - Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.

    Class III - Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope.

    Class IV - Patients with pulmonary hypertension in the inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.

  4. Trough 6MWD at Week 12 [ Time Frame: 12 Weeks ]
    Change in 6MWD from Baseline to trough 6MWD at Week 12. Trough was defined as a 6MWT conducted at least 4 hours following study drug inhalation.

  5. Peak 6MWD at Week 6 [ Time Frame: 6 weeks ]
    Change in peak 6MWD between Baseline and Week 6.

  6. Quality of Life (Minnesota Living With Heart Failure) [ Time Frame: 12 weeks ]
    Quality of life as measured by the Minnesota Living With Heart Failure (MLWHF) questionnaire was evaluated at baseline and at Week 12. The MLWHF questionnaire consists of 21 questions assessing how the patient's heart failure has prevented them from living the way they wanted during the defined time period. Each question was graded by the patient with a numeric value between 0 (No/none) and 5 (very much). These scores were then summed across the 21 questions for a Global Score. Global scores ranged from 0 to 105. These questions were further grouped into Physical (8 of the questions) and Emotional (5 of the questions) dimensions to further characterize the effect of heart failure on the patient's life. Physical scores ranged from 0 to 40, and emotional scores ranged from 0 to 25. For all 3 categories, the lower the score, the better the outcome. Values presented as change from Baseline.

  7. Change in Signs and Symptoms of PAH [ Time Frame: 12 weeks ]
    Signs and symptoms of PAH (Loud P2 sound, Ascites, Right ventricular S3 sound, Dyspnea, Right ventricular S4 sound, Orthopnea, Right ventricular heave, Dizziness, Murmur of tricuspid insufficiency, Syncope, Murmur of pulmonic insufficiency, Chest pain, Hepatomegaly, Palpitations, Jugular venous distension at 45 degrees, Fatigue, Edema) were assessed at Baseline and Week 12. The status of each sign and symptom ("absent" or "present") was assessed at each visit. To assess overall change from baseline in signs and symptoms, a "1" was assigned for each sign and symptom that was "present" at the Week 12 but was "absent" at baseline, a "-1" was assigned for each sign and symptom that was "absent" at Week 12 but was "present" at baseline, and a "0" was assigned for no change. An overall change score at each post-baseline assessment was then calculated by summing these values for all signs and symptoms. The overall change score had the potential to range from -17 to 17.

  8. N-terminal Pro-B-Type Natriuretic Peptide (NT Pro-BNP) [ Time Frame: 12 weeks ]
    Change in NT pro-BNP from Baseline to Week 12. Plasma samples were collected from patients at Baseline and Week 12 in order to measure any change over time in circulating plasma levels of this biomarker.

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

Inclusion Criteria:

  • Clinically stable, pulmonary arterial hypertension diagnosed as either idiopathic or familial PAH, collagen vascular disease associated PAH, HIV PAH, or PAH induced by anorexigens, New York Heart Association (NYHA) Class III or Class IV.
  • Been on a stable dose of 125 mg twice daily (bid) of bosentan OR any stable dose of sildenafil for at least three months prior to study start
  • An unencouraged six minute walk test (6MWT) of between 200 and 450 meters at screening
  • Cardiac catheterization within the past 13 months consistent with PAH, specifically mean pulmonary artery pressure (PAPm) ≥25 mmHg (at rest), pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) ≤15 mmHg, and pulmonary vascular resistance (PVR) >3 mmHg/L/min
  • Within the past 12 months, patients must have had a chest radiograph consistent with the diagnosis of PAH
  • Willing and able to follow all study procedures

Exclusion Criteria:

  • Considering pregnancy, are pregnant and/or lactating
  • PAH due to conditions other than noted in the above inclusion criteria.
  • Have had any change in or discontinued any PAH medication within the last three months, including but not limited to endothelin receptor antagonist (ERA), or calcium channel blockers (CCB) (with the exception of anticoagulants)
  • Have received any prostanoid within the 30 days before screening or are scheduled to receive any during the course of the study
  • Have received any investigational medication within 30 days prior to the start of this study or are scheduled to receive another investigational drug during the course of this study
  • Have a known intolerance to any drug, especially to treprostinil sodium or prostanoids

    - Have an increased risk of hemorrhage

  • Have a new type of chronic therapy (e.g., a different category of vasodilator, diuretic) for PAH added within the last month, except anticoagulants
  • Have any musculoskeletal disease or any other disease that would limit ambulation.

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 identifier (NCT number): NCT00147199

  Hide Study Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294-0006
United States, Arizona
University of Arizona
Tuscon, Arizona, United States, 85724
United States, California
UCSD Medical center
LaJolla, California, United States, 92037
UCLA Medical Center
Torrance, California, United States, 90502
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Orlando Heart Center
Orlando, Florida, United States, 32806
United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-5853
United States, New York
Bethe Israel Medical Center
New York, New York, United States, 10003
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2650
United States, Texas
UTSW Medical Center
Dallas, Texas, United States, 75235
Universitatsklinikfur Innere Medizin II
Wein, Vienna, Austria, 1090
Medical University Graz
Graz, Austria
Universite Libre de Bruxelles
Brussels, Belgium, 1070
University Hospital Gasthuisburg
Leuven, Belgium
Hospital Antoine Beclere
Paris, France, 92141
Univesitatsklinikum Giessen und Marburg GmbH
Geissen, Germany, D-35392
Pulmonary Hypertension Unit
Dublin 7, Ireland
Rambam Medical Center
Haifa, Israel, 31096
The Pulmonary Institute
Jerusalem 91120, Israel
The Pulmonary Institute
Petach Tikvah 49100, Israel
Instituto Malattie dell'Apparato Vascolare
Bologna, Italy
University of Barcelona
Barcelona, Spain, 08036
United Kingdom
Papworth Hospital
Cambridge, United Kingdom, CB3 8RE
Scottish Pulmonary Vascular Unit
Glasgow GII 6NT, United Kingdom
Royal Fee Hospital
London, United Kingdom
Sponsors and Collaborators
United Therapeutics

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: United Therapeutics Identifier: NCT00147199     History of Changes
Other Study ID Numbers: LRX-TRIUMPH 001
First Posted: September 7, 2005    Key Record Dates
Results First Posted: August 12, 2013
Last Update Posted: August 12, 2013
Last Verified: July 2013

Keywords provided by United Therapeutics:
Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
Hypertension, Pulmonary
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Antihypertensive Agents