Study of PAH Subjects With LTOT Use That Have Demonstrated Improved Exercise Tolerance With the Use of Inhaled Nitric

Study Overview
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Brief Summary
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Study of PAH Subjects with LTOT Use that have Demonstrated Improved Exercise Tolerance with the use of Inhaled Nitric Oxide

Detailed Description
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Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Withdrawal Study of Pulmonary Arterial Hypertension(PAH) Subjects with LTOT Use that have Demonstrated Improved Exercise Tolerance with the use of Inhaled Nitric Oxide (INO)

Official Title
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Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Withdrawal Study of Pulmonary Arterial Hypertension(PAH) Subjects With LTOT Use That Have Demonstrated Improved Exercise Tolerance With the Use of Inhaled Nitric Oxide (INO)

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Placebo
* Drug: iNO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form prior to the initiation of any study mandated procedures or assessments Subjects must be enrolled in the PULSE PAH-004 clinical trial and must have been on LTOT and on open-label treatment with iNO 75 mcg/kg IBW/hr for at least 4 months Subjects must have achieved ≥ 30 meter improvement in 6MWD after 4, 8 or 12 months of open-label treatment with iNO 75 mcg/kg IBW/hr as compared to either their PULSE PAH-004 Week 2 end of Run-in OR End of Study (EOS)in PULSE-PAH-004. Subjects are willing and considered in the judgement of the Investigator able to use the INOpulse device continuously for up to 24 hours per day Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) at randomization. All female subjects must use an effective method of birth control to avoid pregnancy. Exclusion Criteria: Subjects with episodes of worsening of PAH in the last 30 days prior to PULSE PAH-007 Baseline/Randomization Subjects that experience Pulmonary Rebound in PULSE-PAH-004 Change in dose or types of PAH specific therapies in the last 30 days prior to Baseline/Randomization Subjects who require treatment with riociguat Subjects who early discontinued drug/device usage due to withdrawal of consent or an adverse event requiring termination from treatment in PULSE PAH-004 Women who are pregnant The concurrent use of the INOpulse device with a continuous airway pressure (CPAP), Bilevel Positive Airway Pressure (BiPAP, or any other positive pressure device.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Cohort 1: Placebo 99.999% Nitrogen<br>Randomized Withdrawal Treatment Period Week 1-8: Placebo at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day Long Term Open Label Extension Period: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day | Drug: Placebo<br>* Placebo at a dose setting of 75 mcg/kg IBW/hr<br>* Other names: Placebo 99.999% Nitrogen;Drug: iNO<br>* iNO at a dose setting of 75 mcg/kg IBW/hr<br>* Other names: Inhaled Nitric Oxide;|
| Active Comparator: Cohort 2: iNO 75 mcg/kg IBW/hr<br>Randomized Withdrawal Treatment Period Week 1-8: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day Long Term Open Label Extension Period: iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day | Drug: iNO<br>* iNO at a dose setting of 75 mcg/kg IBW/hr<br>* Other names: Inhaled Nitric Oxide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical worsening during iNO withdrawal for up to 8 weeks | A clinical worsening event is defined as: Death (all-cause mortality) Atrial septostomy Hospitalization due to worsening of PAH Need to start additional specific PAH treatment Decrease of >15% in 6 Minute Walk Distance from randomization into the study Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV) | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in clinical worsening events that occur during iNO withdrawal for up to 8 weeks between those treated with iNO ≥ 10 months prior to the start of withdrawal of iNO vs. those treated < 10 months prior to initiation of withdrawal to iNO. | A clinical worsening event is defined as: Death (all-cause mortality) Atrial septostomy Hospitalization due to worsening of PAH Need to start additional specific PAH treatment Decrease of >15% in 6 Minute Walk Distance from randomization into the study Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV) | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAH, Inhaled Nitric Oxide, iNO, Long Term Oxygen Therapy, Oxygen therapy