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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00373360
First received: September 7, 2006
Last updated: January 3, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Hypertension
Drug: treprostinil sodium
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rapid Switch From Intravenous Epoprostenol to Intravenous Remodulin® (Treprostinil Sodium) in Patients With Stable Pulmonary Arterial Hypertension: Safety, Efficacy and Treatment Satisfaction

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • Change in the Distance Transversed During the 6 Minute Walk Test From Baseline to Week 8. [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Borg Dyspnea Score Immediately After Six Minute Walk Test From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6-minute walk test. The Borg dyspnea score was assessed immediately following the 6-minute walk test. Scores ranged from 0 (for no shortness of breath) to 10 (for greatest shortness of breath ever experienced).

  • Change in World Health Organization (WHO) Functional Classification of PAH From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]

    Class I: Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope.

    Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. These patients are comfortable at rest, but ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.

    Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope.

    Class IV: Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may be present even at rest. Discomfort is increased by any physical activity.


  • Change in Symptoms of Dyspnea From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The presence or absence of dyspnea was documented. If present, the intensity of dyspnea was rated mild, moderate, or severe.

  • Change in Symptoms of Edema From Baseline to Week 8 [ Time Frame: Baseline to Week 8 ] [ Designated as safety issue: Yes ]
    The presence or absence of edema was documented. If present, the intensity of edema was rated mild, moderate, or severe.

  • Change in Symptoms of Orthopnea From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The presence or absence of orthopnea was documented. If present, the intensity of orthopnea was rated mild, moderate, or severe.

  • Change in Symptoms of Dizziness From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The presence or absence of dizziness was documented. If present, the intensity of dizziness was rated mild, moderate, or severe.

  • Change in Symptoms of Fatigue From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The presence or absence of fatigue was documented. If present, the intensity of fatigue was rated mild, moderate, or severe.

  • Change in Symptoms of Syncope From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The presence or absence of syncope was documented. If present, the intensity of syncope was rated mild, moderate, or severe.

  • Change in Symptoms of Chest Pain From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The presence or absence of chest pain was documented. If present, the intensity of chest pain was rated mild, moderate, or severe.

  • Change in Effectiveness Score on Treatment Satisfaction Scale From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

  • Change in Side-Effects Score on Treatment Satisfaction Scale From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

  • Change in Convenience Score on Treatment Satisfaction Scale From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

  • Change in Global Satisfaction Score on Treatment Satisfaction Scale From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

  • Change in Total Score on Quality of Life Questionnaire From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a health related quality of life instrument specific to PAH. The total score can range from 0 -75; the higher the score, the worse the outcome.

  • Change in Patient Impression of Change in Symptoms of PAH From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Subjects were asked to compare their symptoms of PAH as compared to 8 weeks prior and rate as much better, somewhat better, about the same, somewhat worse, or much worse.

  • Change in Patient Impression of Change on Time Spent Dealing With Therapy From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Subjects were asked to compare their previous experience with Flolan and rate how much time was spent dealing with intravenous Remodulin therapy as much less, somewhat less, about the same, somewhat more, or much more.

  • Change in Patient Impression of Change of Satisfaction With Therapy From Baseline to Week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Subjects were asked to compare their previous experience with Flolan and rate satisfaction with intravenous Remodulin therapy over the past two weeks as much more satisfied, more satisfied, about the same, less satisfied, or much less satisfied.

  • Change in Total Weekly Time Spent to Gather/Set-up Materials Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change in Total Weekly Time Spent to Connect Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change in Total Weekly Time Spent to Change Dressing With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change in Total Weekly Time Spent to Prepare Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change in Total Number of Times Daily Required to Disconnect Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change in Total Number of Times Daily Required to Check Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Change in Total Number of Times Daily Infusion Pump Alarms With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: September 2006
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: treprostinil sodium
rapid switch from intravenous epoprostinol to intravenous remodulin on the CADD ambulatory pump
Other Names:
  • Remodulin
  • Flolan

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00373360

Locations
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
United Therapeutics
Investigators
Principal Investigator: Omar Minai, MD The Cleveland Clinic
  More Information

No publications provided

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00373360     History of Changes
Other Study ID Numbers: RIV-PH-411
Study First Received: September 7, 2006
Results First Received: October 19, 2012
Last Updated: January 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by United Therapeutics:
pulmonary hypertension
PAH
Remodulin
treprostinil
Quality of Life
Rapid Switch

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Epoprostenol
Treprostinil
Tezosentan
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on July 28, 2014