This is a placebo-controlled, double-blind, parallel, randomized, two-part, dose-confirming clinical study characterizing the pharmacodynamic effects of pulsed iNO using the combination product, inhaled nitric oxide/INOpulse DS-C vs. placebo in subjects with World Health Organization (WHO) Group 3 pulmonary hypertension (PH) associated with Chronic Obstructive Pulmonary Disease (COPD) on Long Term Oxygen Therapy (LTOT).
This two-part study is designed to confirm the dose of inhaled nitric oxide (NO), administered through an investigational pulsed delivery device (INOpulse® DS-C) that results in decreased pulmonary arterial systolic pressure (PASP) without significantly affecting systemic oxygenation. In Part A, 80 subjects will be randomized to 1of 4 treatment groups in a 1:1:1:1 ratio (with 20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed iNO at a dose of 0.003 mg/kg IBW/hr, 0.010 mg/kg IBW/hr, or 0.015 mg/kg IBW/hr, with a set pulse width (PW) of 260 milliseconds (ms). Part A subjects assigned to the placebo group will receive nitrogen (N2) at a randomly assigned device setting of 0.003, 0.010 or 0.015 mg/kg IBW/hr with a set PW of 260 ms. Subjects who were randomized in Part A are permitted to participate in Part B of the study. Subjects will need to be re-screened and re-randomized for Part B participation. In Part B, 60 subjects will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (with 20 subjects in each treatment group). Subjects assigned to an iNO group will receive pulsed iNO at either 0.030 mg/kg IBW/hr or 0.075 mg/kg IBW/hr, with a set PW of 260 ms. Part B subjects assigned to placebo will receive N2 at a randomly assigned device setting of 0.030 mg/kg IBW/hr or 0.075 mg/kg IBW/hr with a set PW of 260 ms. Part B will use a skewed block randomization scheme with 10 blocks of 6 subjects as follows: * Blocks 1-3: 3 subjects at 0.030 mg/kg IBW/hr, 1 subject at 0.075 mg/kg IBW/hr, and 2 subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr * Blocks 4-7: 2 subjects at 0.030 mg/kg IBW/hr, 2 subjects at 0.075 mg/kg IBW/hr, and 2 subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr * Blocks 8-10: 1 subject at 0.030 mg/kg IBW/hr, 3 subjects at 0.075 mg/kg IBW/hr, and 2 subjects randomly assigned to placebo either 0.030 or 0.075 mg/kg IBW/hr
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
159
Subjects will be treated with nitric oxide by means of an INOpulse DS-C device using an INOpulse nasal cannula.
Subjects will be treated with nitrogen gas by means of an INOpulse DS-C device using an INOpulse nasal cannula.
Jasper Summit Research LLC
Jasper, Alabama, United States
Clinical Trial Connection
Flagstaff, Arizona, United States
Pulmonary Associates P.A.
Phoenix, Arizona, United States
Radin Cardiovascular Medical Associates
Newport Beach, California, United States
Western Connecticut Medical Group PC
Danbury, Connecticut, United States
Change in pulmonary arterial systolic pressure (PASP) from Baseline after treatment with iNO (measured by 2D transthoracic echocardiography with Doppler)
Time frame: baseline to end of treatment (1 day)
The secondary outcome is the occurrence of a decrease ≥ 5 mm Hg of partial pressure of oxygen in arterial blood (PaO2) from Baseline after treatment with iNO
Time frame: baseline to end of treatment (1 day)
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Waterbury Pulmonary Associates
Waterbury, Connecticut, United States
Bay Area Chest Physicians
Clearwater, Florida, United States
Gary J. Richmond, MD, PA
Fort Lauderdale, Florida, United States
East Coast Institute for Research
Jacksonville, Florida, United States
Pulmonary Disease Specialists PA
Kissimmee, Florida, United States
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