Back to resultsSafety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
Primary Purpose
Pulmonary Arterial Hypertension
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
treprostinil
Crono Five ambulatory pump
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring pulmonary hypertension, PAH, Remodulin, treprostinil, Quality of Life, rapid switch
Eligibility Criteria
Inclusion Criteria:
- Age 18 to 65 years
Diagnosis of one of the following WHO Classifications of pulmonary hypertension:
Group 1 pulmonary arterial hypertension
- Idiopathic pulmonary arterial hypertension (IPAH)
- Familial pulmonary arterial hypertension (FPAH)
Associated pulmonary arterial hypertension (APAH):
- collagen vascular disease
- congenital systemic-to-pulmonary shunt repaired greater than 5 years prior to study entry.
- portal hypertension
- drugs and toxins
- 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):
- Total Lung Capacity ≤ 60% (predicted) or
- 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.
Sites / Locations
- University of California San Francisco (UCSF) Medical Center
- THE NEW YORK-PRESBYTERIAN HOSPITAL Weill Cornell Medical Center
- Integris Baptist Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
treprostinil
Arm Description
IV treprostinil continuous infusion via Crono Five infusion pump.
Outcomes
Primary Outcome Measures
Change From Baseline at Week 8 in 6-Minute Walk Distance (6MWD)
The administration of the 6MWD test and specifications of the testing area were consistent with the American Thoracic Society guidelines and the usual practice of the investigative site [American Thoracic Society (ATS) guidelines; 2002].
Secondary Outcome Measures
Change From Baseline at Week 8 in Borg Dyspnea Score Immediately After Six Minute Walk Test
The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6-Minute Walk Test. Scores range from 0 (for the best condition) to 10 (for the worst condition).
Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification
WHO functional class is a system to help clinicians determine how limited a patient is in their ability to do the activities of daily living. The scale ranges from class I to class IV. In general, patients with more severe Pulmonary Hypertension (PH) tend to have a higher functional class.
Change From Baseline at Week 8 in Symptoms of PAH- Fatigue
The presence or absence of fatigue was documented. If present, the intensity of fatigue was rated mild, moderate, or severe.
Change From Baseline at Week 8 in Symptoms of PAH- Dyspnea
The presence or absence of dyspnea was documented. If present, the intensity of dyspnea was rated mild, moderate, or severe.
Change From Baseline at Week 8 in Symptoms of PAH- Edema
The presence or absence of edema was documented. If present, the intensity of edema was rated mild, moderate, or severe.
Change From Baseline at Week 8 in PAH Symptoms- Orthopnea
The presence or absence of orthopnea was documented. If present, the intensity of orthopnea was rated mild, moderate, or severe.
Change From Baseline at Week 8 in PAH Symptoms- Dizziness
The presence or absence of dizziness was documented. If present, the intensity of dizziness was rated mild, moderate, or severe.
Change From Baseline at Week 8 in PAH Symptoms- Syncope
The presence or absence of syncope was documented. If present, the intensity of syncope was rated mild, moderate, or severe.
Change From Baseline at Week 8 in PAH Symptoms- Chest Pain
The presence or absence of chest pain was documented. If present, the intensity of chest pain was rated mild, moderate, or severe.
Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol
A Drug Administration Activities Diary, used by subjects to record in detail the amount of time (in minutes) spent on specifically-defined drug preparation/administration activities (e.g. diluting drug, preparing reservoir, and changing tubing), was completed over a 7-day period during the Screening period while on epoprostenol and repeated at Week 7 following transition to Remodulin.
Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)
The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), a validated PAH-specific instrument consisting of 65 items used to assess symptoms, functioning and QOL. The CAMPHOR was completed at Baseline and at Week 8. The CAMPHOR consists of 3 scales: 1. A 25-item overall symptoms scale scored 0-25, with a higher score indicating the presence of more symptoms. 2. A 15 item Activity/Functioning scale scored 0-30, where a low score indicates good functioning. 3. A 25-item QoL scale scored 0-25, with a high score indicating poor QoL. Additionally, a total score was recorded by adding up the the scores from the 3 above scales. The Symptom and QoL scales have dichotomous ('True'/'Not true') response options while the Activity/Functioning scale has three-point ('Able to do on own without difficulty'/'Able to do on own with difficulty'/'Unable to do on own') response options. Reduction in score denotes improved heath status.
Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM)
The Treatment Satisfaction Questionnaire for Medication (TSQM), a validated generic measure of treatment satisfaction consisting of 14 Likert-response items comprising four domains: Effectiveness, Side Effects, Convenience, and Global Satisfaction. The TSQM was completed at baseline and at Week 8. The TSQM consists of 13 items that made up three specific scales (Effectiveness, Side effects, Convenience) and one global satisfaction scale. TSQM items are scaled using either a 5-point or 7-point scale. Five-point scales are used for unidimensional continua (e.g. extremely satisfied to not at all), while 7-point scales are used for bipolar continua (e.g., extremely positive to extremely negative. Non-neutral midpoints are used for 7-point scales, resulting in a greater range of positive response options than negative options for these items. Scale scores are transformed into scores ranging from 0 to 100, with a higher score indicating more satisfaction.
Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only)
A Patient Global Impression of Change Questionnaire, which consists of three items that ask the subject to rate changes (much better, somewhat better, about the same, somewhat worse, much worse) in their symptoms of PAH, the amount of time spent on activities associated with preparing and administering PAH therapy, and their satisfaction with their PAH therapy since transitioning from epoprostenol to intravenous Remodulin was conducted at Week 8 only and responses are reported as frequency distributions.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00439946
Brief Title
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
2. Study Status
Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Why Stopped
Study closed due to limited availability of eligible subjects and competition by for enrollment by other studies
Study Start Date
February 2007 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
pulmonary hypertension, PAH, Remodulin, treprostinil, Quality of Life, rapid switch
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
treprostinil
Arm Type
Experimental
Arm Description
IV treprostinil continuous infusion via Crono Five infusion pump.
Intervention Type
Drug
Intervention Name(s)
treprostinil
Other Intervention Name(s)
Remodulin
Intervention Description
rapid switch from intravenous epoprostenol on the CADD ambulatory pump to intravenous Remodulin on the Crono Five ambulatory pump
Intervention Type
Device
Intervention Name(s)
Crono Five ambulatory pump
Intervention Description
Used for administration of IV Remodulin (treprostinil)
Primary Outcome Measure Information:
Title
Change From Baseline at Week 8 in 6-Minute Walk Distance (6MWD)
Description
The administration of the 6MWD test and specifications of the testing area were consistent with the American Thoracic Society guidelines and the usual practice of the investigative site [American Thoracic Society (ATS) guidelines; 2002].
Time Frame
Week 8
Secondary Outcome Measure Information:
Title
Change From Baseline at Week 8 in Borg Dyspnea Score Immediately After Six Minute Walk Test
Description
The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6-Minute Walk Test. Scores range from 0 (for the best condition) to 10 (for the worst condition).
Time Frame
Week 8
Title
Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification
Description
WHO functional class is a system to help clinicians determine how limited a patient is in their ability to do the activities of daily living. The scale ranges from class I to class IV. In general, patients with more severe Pulmonary Hypertension (PH) tend to have a higher functional class.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in Symptoms of PAH- Fatigue
Description
The presence or absence of fatigue was documented. If present, the intensity of fatigue was rated mild, moderate, or severe.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in Symptoms of PAH- Dyspnea
Description
The presence or absence of dyspnea was documented. If present, the intensity of dyspnea was rated mild, moderate, or severe.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in Symptoms of PAH- Edema
Description
The presence or absence of edema was documented. If present, the intensity of edema was rated mild, moderate, or severe.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in PAH Symptoms- Orthopnea
Description
The presence or absence of orthopnea was documented. If present, the intensity of orthopnea was rated mild, moderate, or severe.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in PAH Symptoms- Dizziness
Description
The presence or absence of dizziness was documented. If present, the intensity of dizziness was rated mild, moderate, or severe.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in PAH Symptoms- Syncope
Description
The presence or absence of syncope was documented. If present, the intensity of syncope was rated mild, moderate, or severe.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in PAH Symptoms- Chest Pain
Description
The presence or absence of chest pain was documented. If present, the intensity of chest pain was rated mild, moderate, or severe.
Time Frame
Week 8
Title
Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol
Description
A Drug Administration Activities Diary, used by subjects to record in detail the amount of time (in minutes) spent on specifically-defined drug preparation/administration activities (e.g. diluting drug, preparing reservoir, and changing tubing), was completed over a 7-day period during the Screening period while on epoprostenol and repeated at Week 7 following transition to Remodulin.
Time Frame
Week 8
Title
Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)
Description
The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), a validated PAH-specific instrument consisting of 65 items used to assess symptoms, functioning and QOL. The CAMPHOR was completed at Baseline and at Week 8. The CAMPHOR consists of 3 scales: 1. A 25-item overall symptoms scale scored 0-25, with a higher score indicating the presence of more symptoms. 2. A 15 item Activity/Functioning scale scored 0-30, where a low score indicates good functioning. 3. A 25-item QoL scale scored 0-25, with a high score indicating poor QoL. Additionally, a total score was recorded by adding up the the scores from the 3 above scales. The Symptom and QoL scales have dichotomous ('True'/'Not true') response options while the Activity/Functioning scale has three-point ('Able to do on own without difficulty'/'Able to do on own with difficulty'/'Unable to do on own') response options. Reduction in score denotes improved heath status.
Time Frame
Baseline and Week 8
Title
Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM)
Description
The Treatment Satisfaction Questionnaire for Medication (TSQM), a validated generic measure of treatment satisfaction consisting of 14 Likert-response items comprising four domains: Effectiveness, Side Effects, Convenience, and Global Satisfaction. The TSQM was completed at baseline and at Week 8. The TSQM consists of 13 items that made up three specific scales (Effectiveness, Side effects, Convenience) and one global satisfaction scale. TSQM items are scaled using either a 5-point or 7-point scale. Five-point scales are used for unidimensional continua (e.g. extremely satisfied to not at all), while 7-point scales are used for bipolar continua (e.g., extremely positive to extremely negative. Non-neutral midpoints are used for 7-point scales, resulting in a greater range of positive response options than negative options for these items. Scale scores are transformed into scores ranging from 0 to 100, with a higher score indicating more satisfaction.
Time Frame
Baseline and Week 8
Title
Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only)
Description
A Patient Global Impression of Change Questionnaire, which consists of three items that ask the subject to rate changes (much better, somewhat better, about the same, somewhat worse, much worse) in their symptoms of PAH, the amount of time spent on activities associated with preparing and administering PAH therapy, and their satisfaction with their PAH therapy since transitioning from epoprostenol to intravenous Remodulin was conducted at Week 8 only and responses are reported as frequency distributions.
Time Frame
Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 to 65 years
Diagnosis of one of the following WHO Classifications of pulmonary hypertension:
Group 1 pulmonary arterial hypertension
Idiopathic pulmonary arterial hypertension (IPAH)
Familial pulmonary arterial hypertension (FPAH)
Associated pulmonary arterial hypertension (APAH):
collagen vascular disease
congenital systemic-to-pulmonary shunt repaired greater than 5 years prior to study entry.
portal hypertension
drugs and toxins
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):
Total Lung Capacity ≤ 60% (predicted) or
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Remzi Bag, MD
Organizational Affiliation
INTEGRIS Baptist Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Evelyn Horn, MD
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Teresa DeMarco, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California San Francisco (UCSF) Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
THE NEW YORK-PRESBYTERIAN HOSPITAL Weill Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Integris Baptist Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73122
Country
United States
12. IPD Sharing Statement
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Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
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