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A Phase 2 Placebo-controlled, Randomized, Double-blind Clinical Study to Assess the Efficacy, Safety and Tolerability of Two Doses of Pulsed, Inhaled Nitric Oxide (iNO) in Patients with PAH

Raymond Benza


Robyn Barst


John Granton

David Badesch


Adaani Frost

Harrison Farber


Naushad Hirani

Wendy Hill


Shelley Shapiro


C. Gregory Elliott


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Conference: 2015 PH Professional Network Symposium

Release Date: 09.17.2015

Presentation Type: Abstracts

File Download: 2015 Symposium Abstract - 1002

File Size: (243 kb)

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Purpose

To assess the efficacy, safety and tolerability of pulsed iNO in patients with WHO Group 1 PAH.

Background

Inhaled nitric oxide is a selective pulmonary vasodilator. Clinical experience suggests that iNO has the potential to treat ambulatory patients with pulmonary hypertension, including those with WHO Group 1 (PAH).

Methods

The primary endpoint was change in pulmonary vascular resistance (PVR), and secondary endpoints included change in 6 minute walk distance (6MWD), WHO functional class (FC), and SF-36 Physical component summary (PCS), all from randomization to week 16.

Patients were randomized (in a 1:1:1 ratio) to receive either placebo (N2) or pulsed NO at doses of either 25 or 75 mcg/kg ideal body weight/hr (25 or 75 mcg). iNO was delivered via nasal cannula using the INOpulse device.

Results

80 subjects were recruited. The majority of subjects were female (79%), white (89%) and had idiopathic PAH (74%). Subjects randomized to placebo had a lower % on long term oxygen therapy (LTOT). At 16 weeks, there were non-statistically significant trends toward lower PVR in the iNO cohorts compared to placebo (see table), and a slight trend toward increased 6MWD in the 75 mcg/kg dose group. Treatment effect was minimal on FC and PCS endpoints.

2015SymposiumAbstract1002-Table1

In exploratory analyses (see table), subjects using LTOT at baseline appeared more adherent to using the device: (retrospectively defined as ≥ 12h/day) 70% vs. 33% not using LTOT. This observation drove non-scheduled, exploratory analyses by LTOT use. In the LTOT users, a placebo controlled decrease in PVR was observed and the 6MWD improved in the 75 mcg dose group. There was a <15% decline on 6MWD in non-LTOT users.The safety of iNO appeared acceptable: subjects experiencing serious adverse events (SAE) numbered 4 on placebo, 4 in the 25 dose group and 9 in the 75 dose group while drug-related SAE occurred in 0, 1, & 1 subject, respectively.

Conclusion

In the ITT population, iNO did not significantly affect the PVR or 6MWD in patients with PAH. Minimal differences were seen for WHO functional class and PCS endpoints. Safety of iNO appeared acceptable. Exploratory analyses suggest settings where increased adherence could be expected, such as use in LTOT, could be a way forward in future studies of iNO in PAH. Phase III trials are in the planning stages.