Effect of iNO on Invasively Derived Pulmonary Pressures in Patients With PAH

Effects of iNO on Invasively Derived Pulmonary Vascular Parameters in Patients With Pulmonary Arterial Hypertension

Pulmonary hypertension is characterized by an increase in the pressures in the blood supply to the lungs greater than a mean pressure of 25mmHg and a concomitant increase in overall pulmonary vascular resistance (PVR). In patients who have remodeling of their pulmonary vasculature, PVR will increase with exercise instead of decreasing as it would in normal patients. Based on published evidence, the investigators intend to investigate the effects of inhaled nitric oxide (iNO) on patients undergoing standard exercise techniques who have separately and previously had an implanted pulmonary artery monitoring device (CardioMems by St Jude Medical, Inc.) placed.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Nitric Oxide

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females age 18 to 80 years with a diagnosis of pulmonary arterial hypertension (WHO Group I pulmonary hypertension).
• Must be able to read and understand English and consent for themselves
• Previously implanted CardioMems continuous PA pressure
• Ambulatory and able to complete 6MWD test.

Exclusion Criteria:

• Pregnant or lactating females; negative pregnancy test as confirmed by evaluation of data from pre-enrolled Risk Evaluation and Mitigation Strategies (REMS) program.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Determination of non-invasive pulmonary pressures by CardioMems device interrogation pre- and post-administration of inhaled nitric oxide at 0.075 mg/kg IBW/hr	Drug: Nitric Oxide; Ambulatory inhaled nitric oxide delivery system and 6 minute walk distance test; Other Names: iNOPulse DS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Ambulatory 6 Minute Walk Distance (6MWD) Pulmonary Artery (PA) Pressures (Systolic, Diastolic, Mean) Between the Post-intervention (iNO+) and Pre-intervention (iNO-) Condition as Measured by the CardioMems Device	Difference between baseline (t=0) and post-intervention (t=2h)	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CardioMems Cardiac Output	Difference between baseline (t=0) and post-intervention (t=2h)	2 hours
Change in 6 Minute Walk Distance (6MWD)	Difference (in distance walked between 2 set points over 6 minutes) at baseline (t=0) to post-intervention (t=2h).	2 hours
Change in O2 Saturations		2 hours
Change in Modified Borg Dyspnea Scale	The Modified Borg Dyspnea scale measures patient's subjective analysis of dyspnea from 0 ("nothing at all") to 10 ("maximal") during the 6MWD test with the highest value recorded and difference calculated between baseline (t=0) and post-intervention (t=2h).	2 hours
Change in O2 Requirements	Number of patients that required more or less oxygen by nasal prongs during the course of the study.	2 hours
Change in Mean Arterial Pressure	Difference between baseline (t=0) and post-intervention (t=2h).	2 hours
Change in Heart Rate	Difference between baseline (t=0) and post-intervention (t=2h)	2 hours
Change in Rate Pressure Product	Difference between baseline (t=0) and post-intervention (t=2h)	2 hours
Change in Right Ventricular (RV) Power	Difference between baseline (t=0) and post-intervention (t=2h)	2 hours
Change in Stroke Volume	Difference between baseline (t=0) and post-intervention (t=2h)	2 hours
Change in RV Stroke Work Index	Difference between baseline (t=0) and post-intervention (t=2h)	2 hours

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Investigators: Principal Investigator: Raymond L Benza, MD, West Penn Allegheny Health System

Publications and helpful links

General Publications

• Frantz RP, Benza RL, Kjellstrom B, Bourge RC, Barst RJ, Bennett TD, McGoon MD. Continuous hemodynamic monitoring in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2008 Jul;27(7):780-8. doi: 10.1016/j.healun.2008.04.009. Epub 2008 Jun 2.
• Hasuda T, Satoh T, Shimouchi A, Sakamaki F, Kyotani S, Matsumoto T, Goto Y, Nakanishi N. Improvement in exercise capacity with nitric oxide inhalation in patients with precapillary pulmonary hypertension. Circulation. 2000 May 2;101(17):2066-70. doi: 10.1161/01.cir.101.17.2066.
• Kjellstrom B, Frantz RP, Benza RL, Bennett T, Bourge RC, McGoon MD. Hemodynamic ranges during daily activities and exercise testing in patients with pulmonary arterial hypertension. J Card Fail. 2014 Jul;20(7):485-91. doi: 10.1016/j.cardfail.2014.04.019. Epub 2014 May 9.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: March 26, 2016
• First Submitted That Met QC Criteria: April 6, 2016
• First Posted (Estimate): April 12, 2016

Study Record Updates

• Last Update Posted (Actual): September 24, 2018
• Last Update Submitted That Met QC Criteria: August 24, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Exercise; 6 minute walk test; Inhaled nitric oxide; CardioMems
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: RC6167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: With sponsor to provide statistical analysis