Inhaled Nitrite in Subjects With Pulmonary Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01431313
First received: September 6, 2011
Last updated: November 20, 2015
Last verified: November 2015
  Purpose

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.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Inhaled Nitrite
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Change in pulmonary vascular resistance [ Time Frame: from time zero, at times 15, 30 and 45 minutes of nebulization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 50
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)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 78 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Diagnosis of RHC confirmed WHO Group I PAH (n=20)

Idiopathic, primary or familial pulmonary arterial hypertension • PAH associated with one of the following connective tissue diseases:

PAH associated with exposure to drugs and toxins (eg, anorexigens, L-tryptophan, toxic rapeseed oil)

-Stable PAH for at least 3 months if on therapy This patient population is closed to enrollment. Target enrollment of 20 subjects has been met

WHO Group II Pulmonary Hypertension (n=20) Pulmonary capillary wedge pressure (PWCP) > 15 AND Transpulmonary Gradient (TPG) > 12

WHO Group III PH (n = 10)

  • Has WHO functional class II-IV symptoms
  • Had the diagnosis of PH confirmed by a cardiac catheterization Both WHO Group I PAH and WHO Group III PH

WHO GROUP I (PAH), II and III(PH)

  • Age 18-78
  • Able to participate in right heart catheterization.
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study;
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;

Exclusion Criteria:

  • Age less than 18 years or greater than 78 years.
  • Baseline systemic hypotension, defined as MAP less than 50 mmHg;
  • Required intravenous inotropes within 30 days prior to study participation;
  • Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mm Hg or sitting diastolic blood pressure >100 mm Hg at Screening;
  • Has a history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as mild to severe hepatic impairment (Child-Pugh Class B-C);
  • Has chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at Screening or requires dialytic support;
  • Has a hemoglobin concentration <9 g/dL at Screening;
  • History of atrial septostomy within 6 months prior from Day 1 visit;
  • Repaired or unrepaired congenital heart disease (CHD);
  • Pericardial constriction;
  • Restrictive or congestive cardiomyopathy;
  • Left ventricular ejection fraction <40% by multiple gated acquisition scan (MUGA), angiography or echocardiography;
  • Symptomatic coronary disease with demonstrable ischemia;
  • Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study;
  • Has a psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study. This includes subjects with a recent history of abusing alcohol or illicit drugs 30 days prior to study screening Day 0 and for the duration of the study;
  • Poorly controlled asthma defined by active wheezing and/or cough with FEV1 < 70% predicted, responsive to inhaled BD (>15% increase in FEV1 with BD);
  • Investigators, study staff or their immediate families;
  • Clinically significant intercurrent illness (including lower respiratory tract infection) or clinically significant surgery within 4 weeks before the administration of study drug;
  • Personal or family history of RBC CYP B5 reductase deficiency;
  • Known or suspected hypersensitivity or allergic reaction to sodium nitrite;
  • Personal history of glucose-6-phosphate dehydrogenase (G6PD) deficiency or any contraindication to receiving methylene blue;
  • If female, is pregnant or breast feeding, or has a positive pregnancy test result predose;
  • Receipt of an investigational product or device, or participation in a drug research study within a period of 15 days (or 5 half-lives of the drug, whichever is longer) before the first dose of study drug;
  • Blood loss or blood donation >550 mL within 90 days or plasma donation >500 mL within 14 days before administration of study drug;
  • RHC < 2 weeks from treatment visit unless clinically indicated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431313

Contacts
Contact: Marc A. Simon, MD 412-802-3131 simoma@upmc.edu

Locations
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Marc A. Simon, MD    412-802-3131    simoma@upmc.edu   
Contact: Pamela M. White, RN    412-647-2931    whitepm@upmc.edu   
Principal Investigator: Marc A. Simon, MD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Marc A. Simon, MD University of Pittsburgh
  More Information

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01431313     History of Changes
Other Study ID Numbers: PRO11080686 
Study First Received: September 6, 2011
Last Updated: November 20, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
pulmonary arterial hypertension

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 25, 2016