Pulmonary HypertensionPhase 3TRIUMPHNCT00147199
Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (PAH)
A Phase 3 study testing Inhaled treprostinil in people with Pulmonary Hypertension, run by United Therapeutics at 30 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Inhaled treprostinil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 235 participants
- Where
- 30 sitesin 10 countries
- Study dates
- Jun 2005to Oct 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
30 sites in 10 countries.
30 sites in 10 countries
United States15 sites
University of Michigan
Ann Arbor, Michigan, 48109-5853
University of Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21205
University of Alabama
Birmingham, Alabama, 35294-0006
Tufts Medical Center
Boston, Massachusetts, 02111
UTSW Medical Center
Dallas, Texas, 75235
Duke University Medical Center
Durham, North Carolina, 27710
Kansas University Medical Center
Kansas City, Kansas, 66160
UCSD Medical center
La Jolla, California, 92037
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-2650
Bethe Israel Medical Center
New York, New York, 10003
Orlando Heart Center
Orlando, Florida, 32806
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
UCLA Medical Center
Torrance, California, 90502
University of Arizona
Tucson, Arizona, 85724
Israel3 sites
Rambam Medical Center
Haifa, 31096
The Pulmonary Institute
Jerusalem
The Pulmonary Institute
Petach Tikvah 49100
United Kingdom3 sites
Papworth Hospital
Cambridge, CB3 8RE
Scottish Pulmonary Vascular Unit
Glasgow GII 6NT
Royal Fee Hospital
London
Austria2 sites
Medical University Graz
Graz
Universitatsklinikfur Innere Medizin II
Wein, State of Vienna, 1090
Belgium2 sites
Universite Libre de Bruxelles
Brussels, 1070
University Hospital Gasthuisburg
Leuven
About this study
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
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.
Read the 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.
- Conditions
- Pulmonary Hypertension
- Being tested
- Inhaled treprostinil, Placebo inhalation solution
- Keywords
- Pulmonary Arterial Hypertension
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled treprostinilDrug
Also called Tyvaso
Doses are titrated to 9 breaths four times daily. Each breath produces an 18 mcg dose of inhaled treprostinil.
Placebo inhalation solutionDrug
Also called Placebo
Doses are titrated to 9 breaths four times daily.
| Study group | Role | What they receive |
|---|---|---|
| Inhaled treprostinil | Experimental | 0.9 mg/mL treprostinil for inhalation supplied in 2.9mL ampoules for use in ultra sonic nebulizer Receives: Drug: Inhaled treprostinil |
| Placebo | Placebo comparator | Placebo inhalation solution for use in ultrasonic nebulizer Receives: Drug: Placebo inhalation solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Secondary outcomes (8)
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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.
Measured: 12 Weeks
Peak 6MWD at Week 6
Change in peak 6MWD between Baseline and Week 6.
Measured: 6 weeks
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2005 (estimated)
- Study startJun 2005
- Primary completionOct 2007
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by United TherapeuticsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 235 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00147199
- Sponsor's protocol ID
- LRX-TRIUMPH 001
- Acronym
- TRIUMPH
- Status last verified
- Jul 2013
- First submitted
- 2 Sep 2005
- Last updated
- 2 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 20430262
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00147199
- Acronym / sponsor ID
- TRIUMPH / LRX-TRIUMPH 001
- Conditions
- Pulmonary Hypertension
- Keywords
- Pulmonary Arterial Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 235 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Oct 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 7 Sep 2005 (estimated)
- Results
- Posted 12 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled treprostinil | Experimental | Drug: Inhaled treprostinil0.9 mg/mL treprostinil for inhalation supplied in 2.9mL ampoules for use in ultra sonic nebulizer |
| Placebo | Placebo comparator | Drug: Placebo inhalation solutionPlacebo inhalation solution for use in ultrasonic nebulizer |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inhaled treprostinilAlso: TyvasoDoses are titrated to 9 breaths four times daily. Each breath produces an 18 mcg dose of inhaled treprostinil. | Drug | Inhaled treprostinil |
| Placebo inhalation solutionAlso: PlaceboDoses are titrated to 9 breaths four times daily. | Drug | Placebo |
Primary outcome
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
8 secondary outcomes
Clinical Worsening Events
Time frame: 12 weeks
Borg Dyspnea Score
Time frame: 12 weeks
New York Heart Association (NYHA) Functional Classification
Time frame: 12 weeks
Trough 6MWD at Week 12
Time frame: 12 Weeks
Peak 6MWD at Week 6
Time frame: 6 weeks
Quality of Life (Minnesota Living With Heart Failure)
Time frame: 12 weeks
Change in Signs and Symptoms of PAH
Time frame: 12 weeks
N-terminal Pro-B-Type Natriuretic Peptide (NT Pro-BNP)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20430262McLaughlin 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.
- 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.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
30 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Inhaled treprostinil in people with Pulmonary Hypertension, run by United Therapeutics at 30 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Israel, United Kingdom, Austria, Belgium and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak 6-minute Walk Distance (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00147199, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2024.