Safety, Efficacy and Treatment Satisfaction in Patients With PAH Rapidly Switched From Epoprostenol to Remodulin

Condition(s) targeted: Pulmonary Hypertension

Intervention: treprostinil sodium (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: United Therapeutics

Official(s) and/or principal investigator(s):
Omar Minai, MD, Principal Investigator, Affiliation: The Cleveland Clinic

The purpose of this 8-week study is to compare the effects of switching from therapy with epoprostenol or Flolan to IV Remodulin. This study will also assess the effect that changing to Remodulin will have on patient satisfaction with their treatment and impact on quality of life.

Official title: Rapid Switch From Intravenous Epoprostenol to Intravenous Remodulin® (Treprostinil Sodium) in Patients With Stable Pulmonary Arterial Hypertension: Safety, Efficacy and Treatment Satisfaction

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in the Distance Transversed During the 6 Minute Walk Test From Baseline to Week 8.

Secondary outcome:

Change in Borg Dyspnea Score Immediately After Six Minute Walk Test From Baseline to Week 8

Change in World Health Organization (WHO) Functional Classification of PAH From Baseline to Week 8

Change in Symptoms of Dyspnea From Baseline to Week 8

Change in Symptoms of Edema From Baseline to Week 8

Change in Symptoms of Orthopnea From Baseline to Week 8

Change in Symptoms of Dizziness From Baseline to Week 8

Change in Symptoms of Fatigue From Baseline to Week 8

Change in Symptoms of Syncope From Baseline to Week 8

Change in Symptoms of Chest Pain From Baseline to Week 8

Change in Effectiveness Score on Treatment Satisfaction Scale From Baseline to Week 8

Change in Side-Effects Score on Treatment Satisfaction Scale From Baseline to Week 8

Change in Convenience Score on Treatment Satisfaction Scale From Baseline to Week 8

Change in Global Satisfaction Score on Treatment Satisfaction Scale From Baseline to Week 8

Change in Total Score on Quality of Life Questionnaire From Baseline to Week 8

Change in Patient Impression of Change in Symptoms of PAH From Baseline to Week 8

Change in Patient Impression of Change on Time Spent Dealing With Therapy From Baseline to Week 8

Change in Patient Impression of Change of Satisfaction With Therapy From Baseline to Week 8

Change in Total Weekly Time Spent to Gather/Set-up Materials Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol

Change in Total Weekly Time Spent to Connect Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol

Change in Total Weekly Time Spent to Change Dressing With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol

Change in Total Weekly Time Spent to Prepare Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol

Change in Total Number of Times Daily Required to Disconnect Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol

Change in Total Number of Times Daily Required to Check Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol

Change in Total Number of Times Daily Infusion Pump Alarms With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol

Detailed description: Pulmonary arterial hypertension (PAH), which is defined as an elevation in pulmonary arterial pressure and pulmonary vascular resistance, is a severe hemodynamic abnormality common to a variety of diseases and syndromes. Elevation in pulmonary arterial pressure causes an increase in right ventricular afterload, impairing right ventricular function and ultimately leading to inactivity and death. The goal of PAH treatment is to lengthen survival time, to ameliorate symptoms of PAH and to improve health related quality of life (HRQOL). Remodulin® (treprostinil sodium), a stable analogue of prostacyclin, possesses potent pulmonary and systemic vasodilatory and platelet anti-aggregatory actions in vitro and in vivo. Recently, Remodulin received FDA approval for intravenous therapy based upon bioequivalence of the IV and SC routes of administration. Remodulin is more chemically stable than epoprostenol and may offer potential safety and convenience advantages compared to intravenous epoprostenol that may impact Health Related Quality of Life (HRQOL) and/or patient satisfaction. Unlike epoprostenol, Remodulin does not need to be mixed daily and is stable at room temperature eliminating the need for ice packs. Furthermore, since Remodulin remains in the body longer than epoprostenol (4 hrs instead of less than 5 minutes) there is less risk of cardiovascular collapse from a sudden interruption of infusion, such as a line clog. In an open-label study in Europe, patients who were using a type of portable medication pump called the CADD Legacy pump were rapidly switched from Flolan to Remodulin with no serious side effects. This study will examine effects of switching from therapy with epoprostenol or Flolan to IV Remodulin and compare changes in HRQOL and treatment satisfaction before and after rapid switch from epoprostenol to Remodulin in patients with pulmonary hypertension using the CADD legacy pump. Participation in this study will last approximately 10 weeks. Study procedures include routine blood tests, medical history, physical exams, disease evaluation, exercise tests and patient questionnaires. Participants will have 4 visits during the study and will spend at least 1 night in the hospital.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age 18 to 70 years

- Diagnosis of Idiopathic or Familial Pulmonary Arterial Hypertension (PAH)or PAH

associated with a collagen vascular disease or PAH associated with congenital systemic-to-pulmonary shunt repaired greater than 5 years prior to study entry or PAH associated with portal hypertension with mild or moderate hepatic dysfunction (Grade of A or B on the Child-Pugh Classification Scale)or PAH associated with drug or toxins or CTEPH

- WHO Class II-III

- Currently receiving intravenous epoprostenol therapy for at least three months and a

stable dose for at least one month.

- Have central intravenous catheter

- Optimally treated with conventional pulmonary hypertension therapy and clinically

stable for at least one month.

- Mentally and physically capable of learning to administer Remodulin using an

intravenous infusion pump. Exclusion Criteria:

- Nursing or pregnant woman

- Have any other type of PAH due to conditions other than noted in the above inclusion

criteria, including but not limited to PAH related to thrombotic or embolic disease

- Have any other disease that is associated with pulmonary hypertension (e. g. sickle

cell anemia, schistosomiasis)

- Changes to chronic PAH therapy (i. e., new therapy added within last 30 days[including

but not limited to oxygen, a different category of vasodilator, a diuretic, digoxin, bosentan, sildenafil] or PAH medication discontinued within 7 days of study entry.

- Received any prostacyclin or prostacyclin analog except epoprostenol in the past 3

months.

- Central venous line infection within the past 30 days.

- Previous documented evidence of significant parenchymal lung disease

- Evidence or history of left-sided heart disease

- Musculoskeletal disorder or any other disease, which is thought to limit ambulation,

or be connected to a machine that is not portable

- Uncontrolled hypertension, chronic renal insufficiency, or active infection.

- Use of investigational drug within past 30 days.

Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States

Starting date: September 2006
Last updated: January 3, 2013