search
Back to results

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

Primary Purpose

Pulmonary Hypertension

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Inhaled treprostinil
Placebo inhalation solution
Sponsored by
United Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension focused on measuring Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama
  • University of Arizona
  • UCSD Medical center
  • UCLA Medical Center
  • University of Colorado
  • Orlando Heart Center
  • Kansas University Medical Center
  • Johns Hopkins University
  • Tufts Medical Center
  • University of Michigan
  • Bethe Israel Medical Center
  • Duke University Medical Center
  • Allegheny General Hospital
  • Vanderbilt University Medical Center
  • UTSW Medical Center
  • Universitatsklinikfur Innere Medizin II
  • Medical University Graz
  • Universite Libre de Bruxelles
  • University Hospital Gasthuisburg
  • Hospital Antoine Beclere
  • Univesitatsklinikum Giessen und Marburg GmbH
  • Pulmonary Hypertension Unit
  • Rambam Medical Center
  • The Pulmonary Institute
  • The Pulmonary Institute
  • Instituto Malattie dell'Apparato Vascolare
  • University of Barcelona
  • Papworth Hospital
  • Scottish Pulmonary Vascular Unit
  • Royal Fee Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Inhaled treprostinil

Placebo

Arm Description

0.9 mg/mL treprostinil for inhalation supplied in 2.9mL ampoules for use in ultra sonic nebulizer

Placebo inhalation solution for use in ultrasonic nebulizer

Outcomes

Primary Outcome Measures

Peak 6-minute Walk Distance
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

Clinical Worsening Events
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.
Borg Dyspnea Score
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.
New York Heart Association (NYHA) Functional Classification
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.
Trough 6MWD at Week 12
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.
Peak 6MWD at Week 6
Change in peak 6MWD between Baseline and Week 6.
Quality of Life (Minnesota Living With Heart Failure)
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.
Change in Signs and Symptoms of PAH
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.
N-terminal Pro-B-Type Natriuretic Peptide (NT Pro-BNP)
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.

Full Information

First Posted
September 2, 2005
Last Updated
July 11, 2013
Sponsor
United Therapeutics
search

1. Study Identification

Unique Protocol Identification Number
NCT00147199
Brief Title
Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (PAH)
Acronym
TRIUMPH
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 Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
October 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension
Keywords
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
235 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Inhaled treprostinil
Arm Type
Experimental
Arm Description
0.9 mg/mL treprostinil for inhalation supplied in 2.9mL ampoules for use in ultra sonic nebulizer
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo inhalation solution for use in ultrasonic nebulizer
Intervention Type
Drug
Intervention Name(s)
Inhaled treprostinil
Other Intervention Name(s)
Tyvaso
Intervention Description
Doses are titrated to 9 breaths four times daily. Each breath produces an 18 mcg dose of inhaled treprostinil.
Intervention Type
Drug
Intervention Name(s)
Placebo inhalation solution
Other Intervention Name(s)
Placebo
Intervention Description
Doses are titrated to 9 breaths four times daily.
Primary Outcome Measure Information:
Title
Peak 6-minute Walk Distance
Description
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
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Clinical Worsening Events
Description
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.
Time Frame
12 weeks
Title
Borg Dyspnea Score
Description
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.
Time Frame
12 weeks
Title
New York Heart Association (NYHA) Functional Classification
Description
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.
Time Frame
12 weeks
Title
Trough 6MWD at Week 12
Description
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.
Time Frame
12 Weeks
Title
Peak 6MWD at Week 6
Description
Change in peak 6MWD between Baseline and Week 6.
Time Frame
6 weeks
Title
Quality of Life (Minnesota Living With Heart Failure)
Description
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.
Time Frame
12 weeks
Title
Change in Signs and Symptoms of PAH
Description
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.
Time Frame
12 weeks
Title
N-terminal Pro-B-Type Natriuretic Peptide (NT Pro-BNP)
Description
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.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-0006
Country
United States
Facility Name
University of Arizona
City
Tuscon
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
UCSD Medical center
City
LaJolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Orlando Heart Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Kansas University Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5853
Country
United States
Facility Name
Bethe Israel Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2650
Country
United States
Facility Name
UTSW Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Universitatsklinikfur Innere Medizin II
City
Wein
State/Province
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Medical University Graz
City
Graz
Country
Austria
Facility Name
Universite Libre de Bruxelles
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
University Hospital Gasthuisburg
City
Leuven
Country
Belgium
Facility Name
Hospital Antoine Beclere
City
Paris
ZIP/Postal Code
92141
Country
France
Facility Name
Univesitatsklinikum Giessen und Marburg GmbH
City
Geissen
ZIP/Postal Code
D-35392
Country
Germany
Facility Name
Pulmonary Hypertension Unit
City
Dublin 7
Country
Ireland
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
The Pulmonary Institute
City
Jerusalem 91120
Country
Israel
Facility Name
The Pulmonary Institute
City
Petach Tikvah 49100
Country
Israel
Facility Name
Instituto Malattie dell'Apparato Vascolare
City
Bologna
Country
Italy
Facility Name
University of Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Papworth Hospital
City
Cambridge
ZIP/Postal Code
CB3 8RE
Country
United Kingdom
Facility Name
Scottish Pulmonary Vascular Unit
City
Glasgow GII 6NT
Country
United Kingdom
Facility Name
Royal Fee Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
20430262
Citation
McLaughlin VV, Benza RL, Rubin LJ, Channick RN, Voswinckel R, Tapson VF, Robbins IM, Olschewski H, Rubenfire M, Seeger W. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol. 2010 May 4;55(18):1915-22. doi: 10.1016/j.jacc.2010.01.027.
Results Reference
derived
Links:
URL
http://www.phassociation.org
Description
The mission of the Pulmonary Hypertension Association is to seek a cure, and to provide hope, support and education, and to promote awareness and to advocate for the pulmonary hypertension community.

Learn more about this trial

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

We'll reach out to this number within 24 hrs