Hypertension, Pulmonary
Conditions
Keywords
Pulmonary arterial hypertension, treatment satisfaction, rapid switch, remodulin, Quality of life
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.
Interventions
rapid switch from intravenous epoprostenol on CADD ambulatory pump to intravenous treprostinil sodium
Sponsors
United Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Six Minute Walk Distance | Baseline and Week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in WHO Functional Classification | Baseline and Week 8 | Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms. |
| Change in Score on 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 quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning)and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements. |
| Change in Score on Treatment Satisfaction Questionnaire for Medication | Baseline and Week 8 | 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. |
| Change in Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Baseline and 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. Drug Administration Activities Diary results are reported as average time per week spent on drug administration activities |
| Change in PAH Signs and Symptoms- Fatigue | Baseline and Week 8 | The presence or absence of fatigue was documented. If present, the intensity of fatigue was rated mild, moderate, or severe. |
| Change From in Signs and Symptoms of PAH- Edema | Baseline and Week 8 | The presence or absence of edema was documented. If present, the intensity of edema was rated mild, moderate, or severe. |
| Change in Borg Dyspnea Score Immediately After Six Minute Walk | Baseline and Week 8 | The Borg Dyspnea Score is a 10-point scale rating the maximum level of dyspnea experienced after the Six-Minute Walk Test. Scores range from 0 (for the best condition) to 10 (for the worst condition). |
| Change in Signs and Symptoms of PAH- Orthopnea | Baseline and Week 8 | The presence or absence of orthopnea was documented. If present, the intensity of orthopnea was rated mild, moderate, or severe. |
| Change in Signs and Symptoms of PAH- Dizziness | Baseline and Week 8 | The presence or absence of dizziness was documented. If present, the intensity of dizziness was rated mild, moderate, or severe. |
| Change in Signs and Symptoms of PAH- Syncope | Baseline and Week 8 | The presence or absence of syncope was documented. If present, the intensity of syncope was rated mild, moderate, or severe. |
| Change in Signs and Symptoms of PAH- Chest Pain | Baseline and Week 8 | The presence or absence of chest pain was documented. If present, the intensity of chest pain was rated mild, moderate, or severe. |
| Patient Impression of Change Questionnaire | 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 in Signs and Symptoms of PAH- Dyspnea | Baseline and Week 8 | The presence or absence of dyspnea was documented. If present, the intensity of dyspnea was rated mild, moderate, or severe. |
Countries
United States
Participant flow
Recruitment details
The first subject was enrolled in March 2008. Given the limited availability of eligible subjects at the investigative center (stable PH patients on stable epoprostenol therapy) and competition for enrollment by other studies, after an extended recruitment period during which no new subjects were enrolled, the study was subsequently closed.
Participants by arm
| Arm | Count |
|---|---|
| Treprostinil Sodium treprostinil sodium : all subjects underwent a rapid switch from intravenous epoprostenol on CADD ambulatory pump to intravenous treprostinil sodium | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Treprostinil Sodium |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 43.6 years |
| Baseline 6 Minute Walk Distance (6MWD) | 466.6 meters |
| Pulmonary Arterial Hypertension (PAH) etiology Collagen Vascular Disease | 1 participants |
| Pulmonary Arterial Hypertension (PAH) etiology Idiopathic PAH | 5 participants |
| Pulmonary Arterial Hypertension (PAH) etiology Portal Hypertension | 1 participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
| World Health Organization (WHO) functional Class at time of transition Class II | 5 participants |
| World Health Organization (WHO) functional Class at time of transition Class III | 2 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 7 |
| serious Total, serious adverse events | 2 / 7 |
Outcome results
Primary
Change in Six Minute Walk Distance
Time frame: Baseline and Week 8
Population: Two subjects had a Week 8 visit that was outside of the visit window and are included in the summary. One subject died prior to Week 8 assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil Sodium | Change in Six Minute Walk Distance | -14 meter | Standard Deviation 63.7 |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.69Wilcoxon signed-rank test
Secondary
Change From in Signs and 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: Baseline and Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change From in Signs and Symptoms of PAH- Edema | Improved | 0 participants |
| Treprostinil Sodium | Change From in Signs and Symptoms of PAH- Edema | No Change | 3 participants |
| Treprostinil Sodium | Change From in Signs and Symptoms of PAH- Edema | Worsened | 3 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.25Wilcoxon sign-rank test
Secondary
Change in Borg Dyspnea Score Immediately After Six Minute Walk
The Borg Dyspnea Score is a 10-point scale rating the maximum level of dyspnea experienced after the Six-Minute Walk Test. Scores range from 0 (for the best condition) to 10 (for the worst condition).
Time frame: Baseline and Week 8
Population: Two subjects had a Week 8 visit that was outside of the visit window and are included in the summary. One subject died prior to Week 8 assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treprostinil Sodium | Change in Borg Dyspnea Score Immediately After Six Minute Walk | 0.67 units on a scale | Standard Deviation 0.52 |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.13Wilcoxon signed-rank test
Secondary
Change in PAH Signs and Symptoms- Fatigue
The presence or absence of fatigue was documented. If present, the intensity of fatigue was rated mild, moderate, or severe.
Time frame: Baseline and Week 8
Population: Two subjects had a Week 8 visit that was outside of the visit window and are included in the summary. One subject died prior to Week 8 assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change in PAH Signs and Symptoms- Fatigue | Improved | 0 participants |
| Treprostinil Sodium | Change in PAH Signs and Symptoms- Fatigue | No Change | 4 participants |
| Treprostinil Sodium | Change in PAH Signs and Symptoms- Fatigue | Worsened | 2 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. 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 test
Secondary
Change in Score on 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 quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning)and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.
Time frame: Baseline and Week 8
Population: Two subjects with a Week 8 visit outside of the visit window are included in the summary. One subject died prior to completing the Week 8 visit. One subject had an incomplete Baseline questionnaire and the CAMPHOR Activity component could not be calculated, therefore N=5 Activity and Total Score Components, and N=6 for Symptom and Quality of Life.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil Sodium | Change in Score on Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | Symptom Score | -2.5 units on a scale | Standard Deviation 2 |
| Treprostinil Sodium | Change in Score on Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | Activitity Score | -0.8 units on a scale | Standard Deviation 2.6 |
| Treprostinil Sodium | Change in Score on Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | Quality of Life Score | -4.4 units on a scale | Standard Deviation 6.7 |
| Treprostinil Sodium | Change in Score on Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) | Total Score | -8.0 units on a scale | Standard Deviation 8.9 |
Comparison: Changes in mean CAMPHOR scores between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. 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 test
Comparison: Activity Score N=5; Baseline component score could not be calculated for one subject. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed rank test
Comparison: Quality of Life Score. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. 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 test
Comparison: Total Score N=5; Baseline Activity component score could not be calculated for one subject. Total Score could not be calculated for this subject.~Wilcoxon signed rank test was used to compare 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: 0.13Wilcoxon signed-rank test
Secondary
Change in Score on Treatment Satisfaction Questionnaire for Medication
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
Population: Two subjects had a Week 8 visit that was outside of the visit window and are included in the summary. One subject died prior to completing the Week 8 visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil Sodium | Change in Score on Treatment Satisfaction Questionnaire for Medication | Effectiveness Score | -9.3 units on a scale | Standard Deviation 13 |
| Treprostinil Sodium | Change in Score on Treatment Satisfaction Questionnaire for Medication | Side-Effects Score | 19.8 units on a scale | Standard Deviation 28.9 |
| Treprostinil Sodium | Change in Score on Treatment Satisfaction Questionnaire for Medication | Convenience Score | 22.2 units on a scale | Standard Deviation 12.2 |
| Treprostinil Sodium | Change in Score on Treatment Satisfaction Questionnaire for Medication | Global Satisfaction Score | -1.2 units on a scale | Standard Deviation 21.4 |
Comparison: Effectiveness Score Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.19Wilcoxon signed-rank test
Comparison: Side-Effects Score. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.19Wilcoxon signed-rank test
Comparison: Convenience Score. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. 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 test
Comparison: Global Satisfaction Score. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.88Wilcoxon signed-rank test
Secondary
Change in Signs and Symptoms of PAH- 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: Baseline and Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Chest Pain | Improved | 0 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Chest Pain | No Change | 5 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Chest Pain | Worsened | 1 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed-rank test
Secondary
Change in Signs and Symptoms of PAH- Dizziness
The presence or absence of dizziness was documented. If present, the intensity of dizziness was rated mild, moderate, or severe.
Time frame: Baseline and Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Dizziness | Worsened | 1 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Dizziness | Improved | 0 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Dizziness | No Change | 5 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed-rank test
Secondary
Change in Signs and 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: Baseline and Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Dyspnea | Improved | 1 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Dyspnea | No Change | 3 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Dyspnea | Worsened | 2 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed-rank test
Secondary
Change in Signs and Symptoms of PAH- Orthopnea
The presence or absence of orthopnea was documented. If present, the intensity of orthopnea was rated mild, moderate, or severe.
Time frame: Baseline and Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Orthopnea | Improved | 0 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Orthopnea | No Change | 4 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Orthopnea | Worsened | 2 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. 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 test
Secondary
Change in Signs and Symptoms of PAH- Syncope
The presence or absence of syncope was documented. If present, the intensity of syncope was rated mild, moderate, or severe.
Time frame: Baseline and Week 8
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Syncope | Improved | 0 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Syncope | No Change | 6 participants |
| Treprostinil Sodium | Change in Signs and Symptoms of PAH- Syncope | Worsened | 0 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed-rank test
Secondary
Change in 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. Drug Administration Activities Diary results are reported as average time per week spent on drug administration activities
Time frame: Baseline and Week 8
Population: Two subjects did not have Week 8 Drug Administration Activity Diaries completed.~Connect Drug and Total Time Components: N=4; One subject did not have data recorded for Connect drug activities. Total time could not be calculated for this subject.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treprostinil Sodium | Change in Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Gather/Set-up | -2.6 minutes | Standard Deviation 4 |
| Treprostinil Sodium | Change in Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Prepare Drug | -39.4 minutes | Standard Deviation 12.8 |
| Treprostinil Sodium | Change in Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Connect Drug | -5.0 minutes | Standard Deviation 11.3 |
| Treprostinil Sodium | Change in Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Change Dressing | 0.0 minutes | Standard Deviation 10.6 |
| Treprostinil Sodium | Change in Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol | Total Time | -44.0 minutes | Standard Deviation 25.2 |
Comparison: Gather/Set-up. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.25Wilcoxon signed-rank test
Comparison: Prepare Drug. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.06Wilcoxon signed-rank test
Comparison: Connect Drug. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.63Wilcoxon signed-rank test
Comparison: Change Dressing. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.88Wilcoxon signed-rank test
Comparison: Total Time. Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 0.13Wilcoxon signed-rank test
Secondary
Change in WHO Functional Classification
Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.
Time frame: Baseline and Week 8
Population: Two subjects had a Week 8 visit that was outside of the visit window and are included in the summary. One subject died prior to Week 8 assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Change in WHO Functional Classification | Improved | 0 participants |
| Treprostinil Sodium | Change in WHO Functional Classification | No change | 5 participants |
| Treprostinil Sodium | Change in WHO Functional Classification | Worsened | 1 participants |
Comparison: Changes between Baseline and Week 8 were assessed using the Wilcoxon signed rank test. A two-sided p value of \< 0.05 was considered statistically significant. No imputation was used for missing values.p-value: 1Wilcoxon signed-rank test
Secondary
Patient Impression of Change Questionnaire
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
Population: Two subjects had a Week 8 visit that was outside of the visit window and are included in the summary. One subject died prior to completing the Week 8 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Symptoms- Much Better | 0 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Symptoms-Somewhat Better | 2 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Symptoms- About the Same | 3 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Symptoms- Somewhat Worse | 1 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Symptoms-Much Worse | 0 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Time Spent- Much Less | 3 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Time Spent- Somewhat Less | 3 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Time Spent- About the Same | 0 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Time Spent- Somewhat More | 0 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Time Spent- Much More | 0 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Satisfaction- Much More Satisfied | 1 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Satisfaction- More Satisfied | 3 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Satisfaction- About the Same | 1 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Satisfaction- Less Satisfied | 1 participants |
| Treprostinil Sodium | Patient Impression of Change Questionnaire | Satisfaction- Much Less Satisfied | 0 participants |