Clinical trial NCT00439946: Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
Official title: Rapid Switch From Intravenous Epoprostenol to Intravenous Remodulin® (Treprostinil Sodium) Using the Crono Five Ambulatory Infusion Pump in Patients With Stable Pulmonary Arterial Hypertension (PAH): Safety, Efficacy and Treatment Satisfaction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pulmonary Arterial Hypertension
Keywords: pulmonary hypertension
PAH
Remodulin
treprostinil
Quality of Life
rapid switch
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-02-26
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this 8-week study is to compare the effects of switching from intravenous Flolan to intravenous Remodulin therapy. Remodulin (treprostinil sodium) is an approved therapy for pulmonary arterial hypertension (PAH). Unlike Flolan, Remodulin does not need to be mixed daily and is stable at room temperature, so there is no need for ice packs. In addition, Remodulin is changed every 48hrs, instead of every 12-24 (with ice packs) or every 8 hours (without ice packs) with Flolan. Flolan is given using a type of portable medication pump called the CADD Legacy infusion pump. In this study, Remodulin will be given using a smaller and lighter medication pump called the Crono Five infusion pump. This study will also assess the effect that changing to Remodulin will have on treatment satisfaction and patient 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 intravenous (IV) and subcutaneous (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. 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 from the CADD legacy pump to a smaller pump called the Crono Five.

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.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 65 years
* Diagnosis of one of the following WHO Classifications of pulmonary hypertension:

  1. Group 1 pulmonary arterial hypertension

     * Idiopathic pulmonary arterial hypertension (IPAH)
     * Familial pulmonary arterial hypertension (FPAH)
     * Associated pulmonary arterial hypertension (APAH):

       1. collagen vascular disease
       2. congenital systemic-to-pulmonary shunt repaired greater than 5 years prior to study entry.
       3. portal hypertension
       4. drugs and toxins
  2. Group 4 pulmonary hypertension due to chronic thromboembolic pulmonary hypertension (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
* received 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.
* Had any PAH medication discontinued within the week prior to study entry.
* Received any prostacyclin or prostacyclin analog except epoprostenol in the past 3 months.
* Had a central venous line infection within the past 30 days.
* Previous documented evidence of significant parenchymal lung disease as evidenced by pulmonary function tests as follows (any one of the following):

  1. Total Lung Capacity ≤ 60% (predicted) or
  2. If Total Lung Capacity is between 60% and 70% (predicted), a High Resolution Computed Tomography (CT) scan must be performed to rule out diffuse interstitial fibrosis or alveolitis
* History of or evidence of left-sided heart disease
* Having any other disease that is associated with pulmonary hypertension (e.g. sickle cell anemia, schistosomiasis).
* Having 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.
* Uncontrolled systemic hypertension as evidenced by a systolic blood pressure greater than 160 millimeters of mercury (mmHg) or diastolic blood pressure greater than 100 mmHg.
* Chronic renal insufficiency as defined by serum creatinine greater than 2.5 milligrams per deciliter (mg/dL) or the requirement for dialysis.
* Receiving an investigational drug, have in place an investigational device, or have participated in an investigational drug study within the past 30 days.
* Active infection, or any other ongoing condition that would interfere with the interpretation of study assessments.
* The presence of any physiological or psychological condition that contraindicates the administration of Remodulin.

Primary outcomes:
measure: Change From Baseline at Week 8 in 6-Minute Walk Distance (6MWD)
timeFrame: Week 8
Secondary outcomes:
measure: Change From Baseline at Week 8 in Borg Dyspnea Score Immediately After Six Minute Walk Test
timeFrame: Week 8
measure: Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification
timeFrame: Week 8
measure: Change From Baseline at Week 8 in Symptoms of PAH- Fatigue
timeFrame: Week 8
measure: Change From Baseline at Week 8 in Symptoms of PAH- Dyspnea
timeFrame: Week 8
measure: Change From Baseline at Week 8 in Symptoms of PAH- Edema
timeFrame: Week 8
measure: Change From Baseline at Week 8 in PAH Symptoms- Orthopnea
timeFrame: Week 8
measure: Change From Baseline at Week 8 in PAH Symptoms- Dizziness
timeFrame: Week 8
measure: Change From Baseline at Week 8 in PAH Symptoms- Syncope
timeFrame: Week 8
measure: Change From Baseline at Week 8 in PAH Symptoms- Chest Pain
timeFrame: Week 8
measure: Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol
timeFrame: Week 8
measure: Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)
timeFrame: Baseline and Week 8
measure: Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM)
timeFrame: Baseline and Week 8
measure: Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only)
timeFrame: Week 8
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) Medical Center
state: California
city: New York
country: United States
facility: THE NEW YORK-PRESBYTERIAN HOSPITAL Weill Cornell Medical Center
state: New York
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
Study officials:
affiliation: INTEGRIS Baptist Medical Center
name: Remzi Bag, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Evelyn Horn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Teresa DeMarco, MD
role: PRINCIPAL_INVESTIGATOR
References: