Inhaled Nitrite in Subjects With Pulmonary Hypertension
This is a single-center, open label phase II study to evaluate the effect of inhaled nitrite delivered in a dose escalation manner on the change in pulmonary vascular resistance (PVR) in subjects with pulmonary arterial hypertension undergoing right heart catheterization.
A total of 50 subjects with a confirmed diagnosis of pulmonary arterial hypertension and meet all inclusion/exclusion criteria will be enrolled in the study which will entail a single right heart catheterization and nebulized nitrite dose of 45mg with one subsequent dosage of 90 mg.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose Escalation Study to Evaluate the Effect of Inhaled Nitrite on Cardiopulmonary Hemodynamics in Subjects With Pulmonary Hypertension|
- Change in pulmonary vascular resistance [ Time Frame: from time zero, at times 15, 30 and 45 minutes of nebulization ] [ Designated as safety issue: No ]
- Change in mean pulmonary artery pressure, transpulmonary gradient and cardiac output [ Time Frame: from time zero, at times 15, 30 and 45 minutes of nebulization ] [ Designated as safety issue: No ]
- Change in systemic blood pressure [ Time Frame: from time zero, at times 15, 30 and 45 minutes of nebulization ] [ Designated as safety issue: Yes ]
- Change in SVR, RV systolic (dP/dtmax/IP, PWRmax/EDV, RV EF, TAPSE), RV diastolic (dP/dtmin, Tau) [ Time Frame: from time zero, at times 15, 30 and 45 minutes of nebulization ] [ Designated as safety issue: No ]RV measurements are completed at baseline, 2nd baseline and final measurements
- Change in pulmonary vascular impedance / Wave Intensity [ Time Frame: from time zero, at times 15, 30 and 45 minutes of nebulization ] [ Designated as safety issue: No ]
- Plasma nitrite concentration in mixed venous blood [ Time Frame: pre-dose, and 15 minutes post each inhaled dosage ] [ Designated as safety issue: No ]
- PCW pullback nitrite levels and cGMP levels [ Time Frame: post-dose ] [ Designated as safety issue: No ]
- Change in pulmonary arterial input impedance [ Time Frame: from time zero, at times 15, 30 and 45 minutes of nebulization ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Experimental: Inhaled Nitrite
Sodium Nitrite Inhalation Solution (AIR001) 45mg dosage with one subsequent escalation dosage of 90mg based on tolerability.
Drug: Inhaled Nitrite
Each patient will receive a starting dose of 45 mg of inhaled nitrite, with one planned subsequent planned dose of 90 mg of inhaled nitrite
Screening Visit:Initial screening evaluations including physical examination, medical history, and clinical laboratory assessments will be conducted to determine study eligibilities during a routine clinic visit at the UPMC HVI, CLC or inpatient at UPMC Presbyterian. Subjects who meet the inclusion criteria and none of the exclusion criteria will be entered into the study.
Day 1: This study visit will occur on the same day subjects are scheduled for their clinically indicated right heart catheterization or who volunteer for a research right heart catheterization for this specific study. Subjects on oral background PAH therapy (ETRA or PDE5I) will be instructed to hold their regimen on the day of the study visit.
Subjects will receive nebulized AIR001 doses escalated based upon safety and tolerability. The dose of inhaled nitrite will be delivered via electronic nebulizer. During the study right heart/pulmonary artery hemodynamics will be measured as well as noninvasive systemic blood pressure monitoring. Subjects will be tested for the changes in pulmonary vascular resistance (PVR) using standard clinical protocol hemodynamic recordings of right atrial, right ventricular, and pulmonary artery pressures, in addition to cardiac output at time zero,
3 Day phone follow up
30 Day follow up visit: All subjects enrolled in the study will be followed for 30 days (+/- 5 day window) after completion of the study treatment. A physical exam and clinical labs will be obtained at this visit.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01431313
|Contact: Marc A. Simon, MDfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Marc A. Simon, MD 412-802-3131 email@example.com|
|Contact: Pamela M. White, RN 412-647-2931 firstname.lastname@example.org|
|Principal Investigator: Marc A. Simon, MD|
|Principal Investigator:||Marc A. Simon, MD||University of Pittsburgh|