Clinical Investigation Into Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension (PAH) (TRIUMPH)
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.
Drug: Inhaled treprostinil
Drug: Placebo inhalation solution
|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|
- 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
- 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.
|Study Start Date:||June 2005|
|Study Completion Date:||October 2007|
|Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
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
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.
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