Clinical trial NCT00643604: Rapid Switch From Flolan to Remodulin in the Outpatient Clinic
Official title: Rapid Switch From Intravenous Epoprostenol to Intravenous Remodulin® (Treprostinil Sodium) in Patients With Stable Pulmonary Arterial Hypertension in the Outpatient Clinic: Safety, Efficacy and Treatment Satisfaction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hypertension, Pulmonary
Keywords: Pulmonary arterial hypertension
treatment satisfaction
rapid switch
remodulin
Quality of life
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2008-03-26
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* Be between 18 years and 70 years of age
* Be male or if female, be physiologically incapable of childbearing or practicing an acceptable method of birth control (women of childbearing potential must have a negative pregnancy test).
* Have a current World Health Organization (WHO) functional classification of II-III status
* Diagnosis of one of the following WHO Classifications of pulmonary hypertension: Group 1 pulmonary arterial hypertension (IPAH, FPAH, APAH);Group 3 pulmonary hypertension associated with lung disease (Mild interstitial lung disease associated with predominant features of right heart failure as seen in Group 1 PAH patients); Group 4 pulmonary hypertension due to chronic thromboembolic pulmonary hypertension (CTEPH)
* In the opinion of the investigator, be hemodynamically stable with no signs or symptoms of disease progression
* Be receiving intravenous epoprostenol therapy for at least three months and a stable dose for at least one month prior to Baseline.
* Have a central intravenous catheter in place.
* Have a baseline six-minute walk distance of at least 150 meters.
* Be optimally treated with conventional pulmonary hypertension therapy and clinically stable for at least one month prior to baseline assessments.
* Be mentally and physically capable of learning to administer Remodulin using an intravenous infusion pump.

Exclusion Criteria:

* Be a nursing or pregnant woman
* Have had a new type of chronic therapy (including but not limited to oxygen, a different category of vasodilator, a diuretic, digoxin, bosentan, sildenafil) for pulmonary hypertension added within the last month.
* Have any PAH medication discontinued within the week prior to study entry.
* Received any prostacyclin or prostacyclin analog except epoprostenol in the past 3 months.
* Have an on-going central venous line infection within the past 30 days.
* Have evidence of predominant left-sided heart disease
* Have any other disease that is associated with pulmonary hypertension (e.g. sickle cell anemia, schistosomiasis).
* Have a musculoskeletal disorder (e.g. arthritis, artificial leg, etc.) or any other disease, which is thought to limit ambulation, or be connected to a machine, which is not portable.
* Have uncontrolled systemic hypertension as evidenced by a systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
* Be receiving an investigational drug, have in place an investigational device, or have participated in an investigational drug study within the past 30 days.
* Have the presence of any physiological or psychological condition that contraindicates the administration of Remodulin.

Primary outcomes:
measure: Change in Six Minute Walk Distance
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Change in WHO Functional Classification
timeFrame: Baseline and Week 8
measure: Change in Borg Dyspnea Score Immediately After Six Minute Walk
timeFrame: Baseline and Week 8
measure: Change in Score on Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)
timeFrame: Baseline and Week 8
measure: Change in Score on Treatment Satisfaction Questionnaire for Medication
timeFrame: Baseline and Week 8
measure: Change in Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol
timeFrame: Baseline and Week 8
measure: Change in PAH Signs and Symptoms- Fatigue
timeFrame: Baseline and Week 8
measure: Change From in Signs and Symptoms of PAH- Edema
timeFrame: Baseline and Week 8
measure: Change in Signs and Symptoms of PAH- Dyspnea
timeFrame: Baseline and Week 8
measure: Change in Signs and Symptoms of PAH- Orthopnea
timeFrame: Baseline and Week 8
measure: Change in Signs and Symptoms of PAH- Dizziness
timeFrame: Baseline and Week 8
measure: Change in Signs and Symptoms of PAH- Syncope
timeFrame: Baseline and Week 8
measure: Change in Signs and Symptoms of PAH- Chest Pain
timeFrame: Baseline and Week 8
measure: Patient Impression of Change Questionnaire
timeFrame: Week 8
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke Health
name: Victor Tapson, MD
role: PRINCIPAL_INVESTIGATOR
References: