Pulmonary Arterial Hypertension
Conditions
Keywords
pulmonary hypertension, PAH, Remodulin, treprostinil, Quality of Life, rapid switch
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.
Interventions
DRUGtreprostinil
rapid switch from intravenous epoprostenol on the CADD ambulatory pump to intravenous Remodulin on the Crono Five ambulatory pump
DEVICECrono Five ambulatory pump
Used for administration of IV Remodulin (treprostinil)
Sponsors
United Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 8 in 6-Minute Walk Distance (6MWD) | Week 8 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification | Week 8 | 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 | Week 8 | 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 | Week 8 | 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 | Week 8 | 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 | Week 8 | 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 | Week 8 | 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 Borg Dyspnea Score Immediately After Six Minute Walk Test | Week 8 | 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 PAH Symptoms- Chest Pain | Week 8 | 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 | Week 8 | 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) | Baseline and Week 8 | 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. The CAMPHOR score range can be from 0 to 80. A 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) | Baseline and Week 8 | The Treatment Satisfaction Questionnaire for Medication (TSQM) is a 14-question questionnaire that measures the level of satisfaction or dissatisfaction patients have with their study medication in 4 areas: effectiveness (3 questions), side effects (5 questions), convenience (3 questions), and global satisfaction (3 questions). With the exception of the first side effects question (a yes or no question), all items have 5 or 7 responses which are scored from 1 (least satisfied) to 5 or 7 (most satisfied). A total score is then summed for each domain on the following scales: effectiveness 1-21, side effects 1-20, convenience 1-21, and global satisfaction 1-17. The TSQM score range can be from 0 to 100. Lower total scores in each domain indicate dissatisfaction with the study medication and higher total scores indicate satisfaction. |
| Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Week 8 | 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. |
| Change From Baseline at Week 8 in PAH Symptoms- Syncope | Week 8 | The presence or absence of syncope was documented. If present, the intensity of syncope was rated mild, moderate, or severe. |
Countries
United States
Participant flow
Recruitment details
Screening was initiated by investigators at participating study sites 7 to 28 days prior to the Baseline visit. The first subject was enrolled on February 20, 2007 and the last subject completed the study on September 30, 2009. After an extended recruitment period during which no new subjects were enrolled, the study was closed in 2011.
Pre-assignment details
A total of ten subjects were screened. Eight were enrolled and completed the study. One subject withdrew their consent prior to enrolling. The second subject failed screening due to low hemoglobin levels. Once enrolled, baseline assessments were completed, and patients underwent rapid switch from epoprostenol to treprostinil infusion.
Participants by arm
| Arm | Count |
|---|---|
| Treprostinil All Subjects transitioned from IV epoprostenol to IV treprostinil.
treprostinil: rapid switch from intravenous epoprostenol on the CADD ambulatory pump to intravenous Remodulin on the Crono Five ambulatory pump | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Treprostinil |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 49.5 years |
| Baseline 6 Minute Walk Distance (6MWD) | 390.5 meters |
| epoprostenol dose | 34.05 ng/kg/min |
| Pulmonary Arterial Hypertension (PAH) etiology cardiovascular disease (CVD) | 2 participants |
| Pulmonary Arterial Hypertension (PAH) etiology IPAH | 6 participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 0 Participants |
| World Health Organization (WHO) functional class at time of transition Class II | 6 participants |
| World Health Organization (WHO) functional class at time of transition Class III | 2 participants |
| Years since PAH diagnosis | 7 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
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 \[American Thoracic Society (ATS) guidelines; 2002\].
Time frame: Week 8
Population: Two subjects did not have Baseline 6MWTs and were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in 6-Minute Walk Distance (6MWD) | -1.2 meters | Standard Deviation 37 |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.84Wilcoxon signed rank
Secondary
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).
Time frame: Week 8
Population: Two subjects did not have Baseline Borg scores and were excluded from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in Borg Dyspnea Score Immediately After Six Minute Walk Test | 0.08 units on a scale | Standard Deviation 1.74 |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Chest Pain | Improved | 0 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Chest Pain | No change | 7 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Chest Pain | Worsened | 1 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing valuesp-value: 1Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Dizziness | Improved | 1 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Dizziness | No change | 5 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Dizziness | Worsened | 2 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing valuesp-value: 0.75Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Orthopnea | Improved | 0 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Orthopnea | No change | 8 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Orthopnea | Worsened | 0 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing valuesp-value: 1Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Syncope | Improved | 0 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Syncope | No change | 8 participants |
| Treprostinil | Change From Baseline at Week 8 in PAH Symptoms- Syncope | Worsened | 0 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing valuesp-value: 1Wilcoxon signed rank
Secondary
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. The CAMPHOR score range can be from 0 to 80. A reduction in score denotes improved heath status.
Time frame: Baseline and Week 8
Population: One subject was missing a questionnaire page of the CAMPHOR; Therefore, the component score of
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | CAMPHOR- Symptom Score | -2.1 units on a scale | Standard Deviation 4.3 |
| Treprostinil | Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | CAMPHOR- Activity Score | 1.0 units on a scale | Standard Deviation 3.9 |
| Treprostinil | Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | CAMPHOR- Quality of Life Score | -3.1 units on a scale | Standard Deviation 3.7 |
| Treprostinil | Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | CAMPHOR- Total Score | -4.3 units on a scale | Standard Deviation 10.7 |
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.31Wilcoxon signed rank
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.84Wilcoxon signed rank
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.03Wilcoxon signed rank
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.22Wilcoxon signed rank
Secondary
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) is a 14-question questionnaire that measures the level of satisfaction or dissatisfaction patients have with their study medication in 4 areas: effectiveness (3 questions), side effects (5 questions), convenience (3 questions), and global satisfaction (3 questions). With the exception of the first side effects question (a yes or no question), all items have 5 or 7 responses which are scored from 1 (least satisfied) to 5 or 7 (most satisfied). A total score is then summed for each domain on the following scales: effectiveness 1-21, side effects 1-20, convenience 1-21, and global satisfaction 1-17. The TSQM score range can be from 0 to 100. Lower total scores in each domain indicate dissatisfaction with the study medication and higher total scores indicate satisfaction.
Time frame: Baseline and Week 8
Population: All 8 participants are included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM) | TSQM- Effectiveness Score | -4.9 units on a scale | Standard Deviation 22.9 |
| Treprostinil | Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM) | TSQM- Side-Effects Score | 7.0 units on a scale | Standard Deviation 19 |
| Treprostinil | Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM) | TSQM- Conveniences Score | 29.2 units on a scale | Standard Deviation 21.4 |
| Treprostinil | Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM) | TSQM- Global Satisfaction Score | -11.6 units on a scale | Standard Deviation 31.7 |
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.55Wilcoxon signed rank
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.5Wilcoxon signed rank
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.01Wilcoxon signed rank
Comparison: Changes in mean TSQM and CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.52Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Dyspnea | Improved | 1 participants |
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Dyspnea | No change | 6 participants |
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Dyspnea | Worsened | 1 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing valuesp-value: 1Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Edema | Improved | 0 participants |
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Edema | No change | 6 participants |
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Edema | Worsened | 2 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing valuesp-value: 0.5Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Fatigue | Improved | 1 participants |
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Fatigue | No change | 4 participants |
| Treprostinil | Change From Baseline at Week 8 in Symptoms of PAH- Fatigue | Worsened | 3 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing valuesp-value: 0.5Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
Population: All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification | Improved | 3 participants |
| Treprostinil | Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification | No change | 3 participants |
| Treprostinil | Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification | Worsened | 2 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed rank
Secondary
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.
Time frame: Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Symptoms- Much Better | 4 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Symptoms- Somewhat Better | 1 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Symptoms- About The Same | 1 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Symptoms- Somewhat Worse | 1 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Symptoms- Much Worse | 1 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Time Spent- Much Less | 5 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Time Spent- Somewhat Less | 2 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Time Spent- About The Same | 0 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Time Spent- Somewhat More | 1 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Time Spent- Much More | 0 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Satisfaction- Much More Satisfied | 4 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Satisfaction- More Satisfied | 2 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Satisfaction- About The Same | 1 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Satisfaction- Less Satisfied | 0 participants |
| Treprostinil | Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only) | Satisfaction- Much Less Satisfied | 1 participants |
Secondary
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.
Time frame: Week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil | Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Gather/set-up | 4.4 minutes | Standard Deviation 32.6 |
| Treprostinil | Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Prepare Drug | -50.4 minutes | Standard Deviation 35.3 |
| Treprostinil | Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Connect drug | -13.1 minutes | Standard Deviation 38.1 |
| Treprostinil | Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Change dressing | 3.9 minutes | Standard Deviation 10.8 |
| Treprostinil | Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Total Time | -55.3 minutes | Standard Deviation 77 |
Comparison: Changes in mean times between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.95Wilcoxon signed rank
Comparison: Changes in mean times between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.02Wilcoxon signed rank
Comparison: Changes in mean times between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.2Wilcoxon signed rank
Comparison: Changes in mean times between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.48Wilcoxon signed rank
Comparison: Changes in mean times between Baseline and Week 8 were assessed using the Wilcoxon signed rank test, comparing the values at Baseline to values at Week 8. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.11Wilcoxon signed rank