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

Pulmonary Hypertension Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00147199
• Other study ID #: LRX-TRIUMPH 001
• Status: Completed
• Phase: Phase 3
• Start date: June 2005
• Est. completion date: October 2007

Study information

• Verified date: July 2013
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 235
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension
• Pulmonary Hypertension

Intervention

Drug:
• Inhaled treprostinil
Doses are titrated to 9 breaths four times daily. Each breath produces an 18 mcg dose of inhaled treprostinil.
• Placebo inhalation solution
Doses are titrated to 9 breaths four times daily.

Locations

Country	Name	City	State
Austria	Medical University Graz	Graz
Austria	Universitatsklinikfur Innere Medizin II	Wein	Vienna
Belgium	Universite Libre de Bruxelles	Brussels
Belgium	University Hospital Gasthuisburg	Leuven
France	Hospital Antoine Beclere	Paris
Germany	Univesitatsklinikum Giessen und Marburg GmbH	Geissen
Ireland	Pulmonary Hypertension Unit	Dublin 7
Israel	Rambam Medical Center	Haifa
Israel	The Pulmonary Institute	Jerusalem 91120
Israel	The Pulmonary Institute	Petach Tikvah 49100
Italy	Instituto Malattie dell'Apparato Vascolare	Bologna
Spain	University of Barcelona	Barcelona
United Kingdom	Papworth Hospital	Cambridge
United Kingdom	Scottish Pulmonary Vascular Unit	Glasgow GII 6NT
United Kingdom	Royal Fee Hospital	London
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	UTSW Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Kansas University Medical Center	Kansas City	Kansas
United States	UCSD Medical center	La Jolla	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Bethe Israel Medical Center	New York	New York
United States	Orlando Heart Center	Orlando	Florida
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UCLA Medical Center	Torrance	California
United States	University of Arizona	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  France,  Germany,  Ireland,  Israel,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 Weeks
Secondary	Peak 6MWD at Week 6	Change in peak 6MWD between Baseline and Week 6.	6 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks
Secondary	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.	12 weeks

External Links

•   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.