Nitric Oxide, GeNO Nitrosyl Delivery System
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension
Intervention: Nitric Oxide
Intervention description: Nitric oxide, 80 ppm in air or oxygen will be administered using the GeNO nitrosyl delivery system with a standard nasal cannula at a flow rate of 4 LPM.
Intervention MeSH terms: Nitric Oxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary aim of the study is to evaluate the safety, tolerability and device performance
      of the GeNO nitrosyl delivery system during RHC. Secondary considerations are to confirm that
      inhaled NO generated by the GeNO nitrosyl delivery system, reduces PVR in patients with
      reversible PH, contains levels of NO2 well below the upper level of acceptable exposure.
      Further, the study aims to demonstrate that patient response to inhaled NO can be used as a
      diagnostic tool with which to determine the proper course of medical action in patients with
      chronic heart failure.

      Patients with chronic heart failure accompanied by pulmonary hypertension and increased
      pulmonary vascular resistance have a number of possible medical therapies available to them.
      The least invasive, and therefore most appealing, option is standard management with
      medication and observation. Alternatively, implantation of a left ventricular assist device
      (LVAD) may be considered, either as a permanent solution or as a bridging strategy to the
      final option, orthotopic heart transplantation (OHT). It is often unclear which route is the
      best medical choice, and a tool to help physicians and patients choose between these
      alternatives would be greatly beneficial.

      It has been shown that chronic heart failure patients that demonstrate irreversible pulmonary
      hypertension, even in the presence of vasodilators, exhibit adverse outcomes after OHT (Tsai
      et al., 2002; Ericson et al., 1990; Murali et al., 1996). It follows that patient response to
      pulmonary vasodilators can, and should be used to classify patients as potential candidates
      for OHT. In particular, patient response to inhaled NO, a known pulmonary vasodilator, can be
      used as a diagnostic tool to assist in deciding which medical route to take.

      With this in mind, the current study aims to demonstrate whether or not NO generated by the
      GeNO nitrosyl delivery system effects a reduction in pulmonary hypertension due to increased
      pulmonary vascular resistance in patients with chronic heart failure. Any demonstrated
      ability of inhaled NO to decrease PVR in patients with reversible PH will support the use of
      patient response to inhaled NO as a diagnostic tool to assist in choosing the most
      appropriate medical therapy for patients with chronic heart failure.
    

Eligibility criteria:

        Inclusion Criteria:

          -  An Institutional Review board (IRB) approved informed consent is signed, dated and
             timed prior to any study-related activities.

          -  Male or female > 18 years of age.

          -  Being evaluated for OHT or LVAD implantation and scheduled to undergo right heart
             catheterization to assess pulmonary vasoreactivity.

          -  Have a confirmed diagnosis of heart failure, (NYHA Class III or IV)

          -  Participant has the ability to understand the requirements of the study and a
             willingness to comply with all study procedures.

          -  Females of childbearing potential with a negative urine pregnancy test, or a
             documented surgical sterilization, or is post-menopausal prior to administration of
             investigational product. Females of childbearing potential must be practicing adequate
             birth control to be eligible. It is the Investigator's responsibility to determine
             whether the Participant has adequate birth control for study participation.

          -  Confirmed pulmonary arterial hypertension at time of RHC:

               -  PAPm > 25mmHg at rest and PVR > 3 Wood units

        Exclusion Criteria:

          -  Be receiving an investigational drug, have in place an investigational device, or have
             participated in an investigational drug study within the past 30 days.

          -  Have had an atrial septostomy.

          -  Have anemia (hemoglobin <10 g/dL), active infection or any other ongoing condition
             that would interfere with the interpretation of study assessments.

          -  Have any serious or life-threatening disease other than conditions (e.g. malignancy
             requiring aggressive chemotherapy, etc.).

          -  Have unstable psychiatric status or be mentally incapable of understanding the
             objectives, nature or consequences of the trial, or any condition, which in the
             investigator's opinion would constitute an unacceptable risk to the participant's
             safety.

          -  Participant is pregnant or lactating