Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Hypertension
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Purpose This study proposes to investigate the safety, tolerability, and feasibility of
      transitioning patients with PAH from intravenous or subcutaneous prostacyclin analogs to
      inhaled treprostinil using a defined protocol. Twenty-one patients from three PH specialty
      referral centers will be enrolled in this 12-week, prospective, open-label study. If subjects
      meet inclusion and exclusion criteria, they will be switched from intravenous or subcutaneous
      prostacyclin analogs to inhaled treprostinil according to a defined transition protocol.

      Background Parenteral prostacyclin analogs improve exercise capacity and survival in patients
      with pulmonary arterial hypertension (PAH), however practical issues can limit their
      tolerability in some patients. The prostacyclin analogue treprostinil has been shown to
      improve exercise capacity and signs/symptoms of PAH, while delivered via four 2-3 minute
      inhalation periods per day. In addition, there is extensive worldwide experience with the
      subcutaneous and intravenous forms of treprostinil, with documented safety, efficacy, and
      tolerability.

      Prior published studies have examined the feasibility of prostacyclin transitions, including
      transition from intravenous epoprostenol to non-parenteral PAH treatments, from subcutaneous
      to intravenous treprostinil, and from intravenous prostanoids to subcutaneous treprostinil.

      There is currently no published experience examining the safety, tolerability and feasibility
      of transitioning patients from parenteral prostanoids to inhaled treprostinil.
    

Intervention name(s): Treprostinil
Intervention type(s): Drug
Intervention description(s): Transition to inhaled treprostinil
Other intervention name(s): Tyvaso
Intervention MeSH terms: Treprostinil
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pulmonary arterial hypertension; inhaled prostacyclin