Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication

NCT01268553 | Completed Phase 4 Results

• 1 other identifier: Tyvaso Switch
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

pulmonary arterial hypertension; inhaled prostacyclin

Outcome Measures

Primary Outcomes (1)

• Number of Participants Without Adverse Events

  The number of adverse events will be recorded at transition, 4 weeks, and 12 weeks.

  12 Weeks

Secondary Outcomes (5)

• Number of Participants Without Clinical Worsening

  12 weeks

• Change in 6-minute Walk Distance

  12 weeks

• VE/VCO

  12 weeks

• CAMPHOR: Cambridge Pulmonary Hypertension Outcome Review; Construct = Quality of Life

  12 q=weeks

• N-terminal Pro BNP Level

  12 weeks

Study Arms (1)

Active treatment

EXPERIMENTAL

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.

Drug: Treprostinil

Interventions

Treprostinil DRUG

Transition to inhaled treprostinil

Also known as: Tyvaso

Active treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead
• United Therapeutics: collaborator

Study Sites (3)

University of Arizona

Tucson, Arizona, 85721, United States

Location

University of CA, San Francisco

San Francisco, California, 94143, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Related Publications (1)

• 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.

  PMID: 28090295 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Ronald Oudiz
• Organization: Los Angeles Biomedical research INst at Harbor-UCLA

roudiz@labiomed.org

310-222-3560

Study Officials

• Ronald J Oudiz, MD

  LA Biomed

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 29, 2010
• First Posted: December 31, 2010
• Study Start: August 1, 2010
• Primary Completion: October 5, 2016
• Study Completion: October 5, 2016
• Last Updated: September 1, 2017
• Results First Posted: September 1, 2017

Record last verified: 2017-08

Locations

US (3)