Clinical trial NCT00147199: Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (PAH)
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Hypertension
Keywords: Pulmonary Arterial Hypertension
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2005-09-07
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Peak 6-minute Walk Distance
timeFrame: 12 weeks
Secondary outcomes:
measure: Clinical Worsening Events
timeFrame: 12 weeks
measure: Borg Dyspnea Score
timeFrame: 12 weeks
measure: New York Heart Association (NYHA) Functional Classification
timeFrame: 12 weeks
measure: Trough 6MWD at Week 12
timeFrame: 12 Weeks
measure: Peak 6MWD at Week 6
timeFrame: 6 weeks
measure: Quality of Life (Minnesota Living With Heart Failure)
timeFrame: 12 weeks
measure: Change in Signs and Symptoms of PAH
timeFrame: 12 weeks
measure: N-terminal Pro-B-Type Natriuretic Peptide (NT Pro-BNP)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: UCSD Medical center
state: California
city: Torrance
country: United States
facility: UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Orlando
country: United States
facility: Orlando Heart Center
state: Florida
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Bethe Israel Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UTSW Medical Center
state: Texas
city: Wein
country: Austria
facility: Universitatsklinikfur Innere Medizin II
state: Vienna
city: Graz
country: Austria
facility: Medical University Graz
city: Brussels
country: Belgium
facility: Universite Libre de Bruxelles
city: Leuven
country: Belgium
facility: University Hospital Gasthuisburg
city: Paris
country: France
facility: Hospital Antoine Beclere
city: Geissen
country: Germany
facility: Univesitatsklinikum Giessen und Marburg GmbH
city: Dublin 7
country: Ireland
facility: Pulmonary Hypertension Unit
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem 91120
country: Israel
facility: The Pulmonary Institute
city: Petach Tikvah 49100
country: Israel
facility: The Pulmonary Institute
city: Bologna
country: Italy
facility: Instituto Malattie dell'Apparato Vascolare
city: Barcelona
country: Spain
facility: University of Barcelona
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Glasgow GII 6NT
country: United Kingdom
facility: Scottish Pulmonary Vascular Unit
city: London
country: United Kingdom
facility: Royal Fee Hospital
Study officials:
References:
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.