Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Hypertension
Intervention: Treprostinil
Intervention description: Transition to inhaled treprostinil
Intervention MeSH terms: Treprostinil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: pulmonary arterial hypertension; inhaled prostacyclin

Summary:

      The purpose of this study is to assess tolerability and clinical effects of transition from
      intravenous (IV, needle in the vein) or subcutaneous (SQ, needle in the skin) to the
      recently-approved inhaled treprostinil (Tyvaso) for the treatment of pulmonary arterial
      hypertension (PAH).

      Our hypothesis is that the transition to inhaled treprostinil will be tolerated by patients.

      The intravenous and subcutaneous drugs epoprostenol and treprostinil received approval for
      treatment of PAH many years ago. While these medications improve exercise capacity and the
      symptoms of PAH, they are given by injection and thus have several side effects, such as pain
      and catheter infection. This has resulted in many patients either refusing to take the
      medication or quitting these medications because of not tolerating them.

      The only other form of prostacyclin treatment available for PAH patients is inhaled. There
      are 2 inhaled prostacyclins approved for PAH, however one of these requires at least 6
      inhalations per day, every day, and takes about 30 minutes to inhale each time. Thus, it has
      not been a regularly-used medication and issues surrounding compliance make it a riskier drug
      to use if patients do not get their full doses every day. The other inhaled medication,
      treprostinil, was approved a few months ago, only needs to be given 4 times a day, and takes
      about 2-3 minutes to inhale.

      Since inhaled treprostinil can be administered easily, it is anticipated that many patients
      will transition from epoprostenol or treprostinil to the recently approved inhaled
      treprostinil, however we do not know if this is a safe or effective way to manage patients.
      Thus, the goal of this prospective study is to gather observational data regarding how that
      switch is made, tolerability of the switch, and, to the extent possible with this
      methodology, assess clinical effects of the switch.

      This is a prospective study. Twenty patients > 18 years old with PAH will be enrolled.
      Patients enrolled will be those in whom a clinical decision to convert from either IV
      epoprostenol, IV treprostinil, or SQ treprostinil to inhaled treprostinil therapy has been
      made. This is usually the result of patients asking to switch to inhaled therapy, but only
      allowed by physicians if they feel the switch would be safe.

      If eligible, and after informed consent, patients will have a history and physical
      examination, a 6 min walk test, a cardiopulmonary exercise test (CPET), blood tests, and a
      symptom questionnaire will be filled out. Patients will then be admitted to the hospital
      where a monitoring catheter will be placed inside the patient's heart and inhaled
      treprostinil will be initiated, while the dose of IV/SQ medication is reduced over about
      24-26 hours.

      Clinical follow-up will be at weeks 1, 4, and 12.

      The procedures above are all part of the routine clinical care that patients would receive if
      they were to be transitioned to inhaled therapy, including the hospitalization and
      catheterization. The criteria for them to be able to be switched are conservative. Pressure
      in their heart and lungs must be low (mPAP < 40 mmHg and RAP <12 mmHg on catheterization),
      and their dose of IV or SQ medication must be low (< 20 ng/kg/min). Regarding the patient
      subset enrolled in this study in whom a clinical decision to convert transition therapy has
      been made, we will try to ensure that our clinical decision-making will not be influenced by
      the need to enroll subjects in the study by explicitly noting the potential for conflict of
      interest with each patient (addressed in the ICF). We will not make a clinical decision for
      our patients based on the desire to fill the study numbers, and every will be made to avoid
      the potential for a perceived conflict of interest.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with WHO group I PAH

          -  Stable patients with NYHA/WHO functional class I or II

          -  Age >18

          -  Treatment for PAH with parenteral prostanoid (IV epoprostenol, IV or SQ treprostinil)
             for at least 90 days

          -  Dose of prostanoid < 20 ng/kg/min

          -  mPAP < 40 mmHg and RAP <12 mmHg on catheterization

          -  Clinical decision to convert from parenteral prostanoid therapy to inhaled
             treprostinil therapy

        Exclusion Criteria:

          -  Concomitant underlying medical condition limiting ability to perform exercise

          -  Addition of new PAH medication within the past 90 days prior to enrollment

          -  Participation in a clinical study involving an investigational drug or device < 4
             weeks prior to the screening visit

          -  Any additional contraindications and precautions specified in the package inserts for
             treprostinil (Tyvaso) not listed above