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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00147199
First received: September 2, 2005
Last updated: July 11, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Pulmonary Hypertension
Drug: Inhaled treprostinil
Drug: Placebo inhalation solution
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • Peak 6-minute Walk Distance [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Change in peak 6MWD between Baseline and Week 6.

  • Quality of Life (Minnesota Living With Heart Failure) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 235
Study Start Date: June 2005
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00147199

  Show 30 Study Locations
Sponsors and Collaborators
United Therapeutics
  More Information

Additional Information:
No publications provided by United Therapeutics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00147199     History of Changes
Other Study ID Numbers: LRX-TRIUMPH 001
Study First Received: September 2, 2005
Results First Received: December 3, 2012
Last Updated: July 11, 2013
Health Authority: United States: Food and Drug Administration
Austria: Federal Ministry for Health and Women
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Ireland: Irish Medicines Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by United Therapeutics:
Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Pharmaceutical Solutions
Treprostinil
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 01, 2014