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Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01268553
Recruitment Status : Completed
First Posted : December 31, 2010
Results First Posted : September 1, 2017
Last Update Posted : September 1, 2017
Sponsor:
Collaborator:
United Therapeutics
Information provided by (Responsible Party):
ronald oudiz, m.d., Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Tracking Information
First Submitted Date  ICMJE December 29, 2010
First Posted Date  ICMJE December 31, 2010
Results First Submitted Date  ICMJE June 6, 2017
Results First Posted Date  ICMJE September 1, 2017
Last Update Posted Date September 1, 2017
Study Start Date  ICMJE August 2010
Actual Primary Completion Date October 5, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2017)
Number of Participants Without Adverse Events [ Time Frame: 12 Weeks ]
The number of adverse events will be recorded at transition, 4 weeks, and 12 weeks.
Original Primary Outcome Measures  ICMJE
 (submitted: December 30, 2010)
Number of adverse events [ Time Frame: 12 Weeks ]
The number of adverse events will be recorded at transition, 4 weeks, and 12 weeks.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2017)
  • Number of Participants Without Clinical Worsening [ Time Frame: 12 weeks ]
    Clinical worsening is defined as any of the following:
    • All-cause mortality
    • Nonelective hospital stay for PAH (with predefined criteria, usually for initiation of intravenous prostanoids, lung transplantation, or septostomy)
    • Disease progression defined as a reduction from baseline in the 6MW test by 15%, confirmed by 2 studies done within 2 weeks plus worsening functional class
  • Change in 6-minute Walk Distance [ Time Frame: 12 weeks ]
    Change in 6-minute walk distance from baseline to 12 weeks.
  • VE/VCO [ Time Frame: 12 weeks ]
    Ventilatory efficiency measured with cardiopulmonary exercise testing
  • CAMPHOR: Cambridge Pulmonary Hypertension Outcome Review; Construct = Quality of Life [ Time Frame: 12 q=weeks ]
    The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a disease specific patient-reported outcome measure which assesses quality of life of patients with pulmonary hypertension (PH). QoL scores (total) range from 0-25, with higher scores indicating worse quality of life
  • N-terminal Pro BNP Level [ Time Frame: 12 weeks ]
    N-terminal pro BNP level
Original Secondary Outcome Measures  ICMJE
 (submitted: December 30, 2010)
  • clinical worsening [ Time Frame: 12 weeks ]
    Clinical worsening is defined as any of the following:
    • All-cause mortality
    • Nonelective hospital stay for PAH (with predefined criteria, usually for initiation of intravenous prostanoids, lung transplantation, or septostomy)
    • Disease progression defined as a reduction from baseline in the 6MW test by 15%, confirmed by 2 studies done within 2 weeks plus worsening functional class
  • 6-minute walk distance [ Time Frame: 12 weeks ]
    6-minute walk distance,
  • VE/VCO [ Time Frame: 12 weeks ]
    Ventilatory efficiency measured with cardiopulmonary exercise testing
  • quality of life [ Time Frame: 12 q=weeks ]
    quality of life using the CAMPHOR questionnaire
  • N-terminal pro BNP level [ Time Frame: 12 weeks ]
    N-terminal pro BNP level
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
Official Title  ICMJE Transition From Parenteral Prostanoids to Inhaled Treprostinil
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE Drug: Treprostinil
Transition to inhaled treprostinil
Other Name: Tyvaso
Study Arms  ICMJE Experimental: Active treatment
This is the only arm in the trial. All enrolled subjects will be attempted to transition to inhaled treprostinil. There is no placebo and control arm.
Intervention: Drug: Treprostinil
Publications * Oudiz R, Agarwal M, Rischard F, De Marco T. An advanced protocol-driven transition from parenteral prostanoids to inhaled trepostinil in pulmonary arterial hypertension. Pulm Circ. 2016 Dec;6(4):532-538. doi: 10.1086/688711.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 31, 2017)
6
Original Estimated Enrollment  ICMJE
 (submitted: December 30, 2010)
21
Actual Study Completion Date  ICMJE October 5, 2016
Actual Primary Completion Date October 5, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01268553
Other Study ID Numbers  ICMJE Tyvaso Switch
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party ronald oudiz, m.d., Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Original Responsible Party Ronald J. Oudiz, MD, LA Biomed
Current Study Sponsor  ICMJE Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE United Therapeutics
Investigators  ICMJE
Principal Investigator: Ronald J Oudiz, MD LA Biomed
PRS Account Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP