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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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ClinicalTrials.gov Identifier: NCT00439946
Recruitment Status : Terminated (Study closed due to limited availability of eligible subjects and competition by for enrollment by other studies)
First Posted : February 26, 2007
Results First Posted : July 17, 2013
Last Update Posted : July 17, 2013
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Interventions Drug: treprostinil
Device: Crono Five ambulatory pump
Enrollment 8

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.
Arm/Group Title Treprostinil
Hide Arm/Group Description

All Subjects transitioned from IV epoprostenol to IV treprostinil initiated to deliver a dose 20% higher than the epoprostenol dose on a ng/kg/min basis. IV treprostinil dosing was titrated without restriction during the eight week follow-up period per the investigator's judgment to optimize the dose for symptomatic benefit based on clinical signs / symptoms, exercise capacity and tolerability.

treprostinil: rapid switch from intravenous epoprostenol on the CADD ambulatory pump to intravenous Remodulin on the Crono Five ambulatory pump

Period Title: Overall Study
Started 8
Completed 8
Not Completed 0
Arm/Group Title Treprostinil
Hide Arm/Group Description

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

Overall Number of Baseline Participants 8
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
<=18 years
0
   0.0%
Between 18 and 65 years
8
 100.0%
>=65 years
0
   0.0%
Age Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants
49.5
(45 to 59)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants
Female
8
 100.0%
Male
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 8 participants
8
Pulmonary Arterial Hypertension (PAH) etiology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 8 participants
IPAH 6
cardiovascular disease (CVD) 2
Years since PAH diagnosis  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants
7
(1.5 to 12.9)
World Health Organization (WHO) functional class at time of transition   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 8 participants
Class II 6
Class III 2
[1]
Measure 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.
epoprostenol dose  
Mean (Full Range)
Unit of measure:  Ng/kg/min
Number Analyzed 8 participants
34.05
(7.7 to 71)
Baseline 6 Minute Walk Distance (6MWD)   [1] 
Mean (Full Range)
Unit of measure:  Meters
Number Analyzed 8 participants
390.5
(294 to 506)
[1]
Measure Description: This measure includes 6 patients. Two subjects did not have Baseline 6-Minute Walk Tests (6MWTs) conducted.
1.Primary Outcome
Title Change From Baseline at Week 8 in 6-Minute Walk Distance (6MWD)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two subjects did not have Baseline 6MWTs and were excluded from this analysis.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: meters
-1.2  (37.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline at Week 8 in Borg Dyspnea Score Immediately After Six Minute Walk Test
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two subjects did not have Baseline Borg scores and were excluded from this analysis.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.08  (1.74)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline at Week 8 in World Health Organization (WHO) Functional Classification
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 3
No change 3
Worsened 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline at Week 8 in Symptoms of PAH- Fatigue
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 1
No change 4
Worsened 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline at Week 8 in Symptoms of PAH- Dyspnea
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 1
No change 6
Worsened 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline at Week 8 in Symptoms of PAH- Edema
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 0
No change 6
Worsened 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline at Week 8 in PAH Symptoms- Orthopnea
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 0
No change 8
Worsened 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline at Week 8 in PAH Symptoms- Dizziness
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 1
No change 5
Worsened 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.75
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline at Week 8 in PAH Symptoms- Syncope
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 0
No change 8
Worsened 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline at Week 8 in PAH Symptoms- Chest Pain
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects transitioned from IV epoprostenol to IV treprostinil were included.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Improved 0
No change 7
Worsened 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00
Comments [Not Specified]
Method Wilcoxon signed rank
Comments [Not Specified]
11.Secondary Outcome
Title Total Weekly Time Spent With the Specific Activities Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: minutes
Gather/set-up 4.4  (32.6)
Prepare Drug -50.4  (35.3)
Connect drug -13.1  (38.1)
Change dressing 3.9  (10.8)
Total Time -55.3  (77.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.95
Comments p-value for: Gather/set-up
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments p-value for: Prepare drug
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments p-value for: Connect drug
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments p-value for: Change dressing
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments p-value for: Total time
Method Wilcoxon signed rank
Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline at Week 8 in Score on Quality of Life (QOL) Questionnaire - The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One subject was missing a questionnaire page of the CAMPHOR; Therefore, the component score of
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
CAMPHOR- Symptom Score (n=7) -2.1  (4.3)
CAMPHOR- Activity Score (n=8) 1.0  (3.9)
CAMPHOR- Quality of Life Score (n=7) -3.1  (3.7)
CAMPHOR- Total Score (n=7) -4.3  (10.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments p-value for: CAMPHOR Symptom Score
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.84
Comments p-value for CAMPHOR Activity Score
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments p-value for CAMPHOR Quality of Life Score
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments p-value for CAMPHOR Total Score
Method Wilcoxon signed rank
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline at Week 8 in Score on Treatment Satisfaction Questionnaire- The Treatment Satisfaction Questionnaire for Medication (TSQM)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All 8 participants are included.
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
TSQM- Effectiveness Score (n=8) -4.9  (22.9)
TSQM- Side-Effects Score (n=8) 7.0  (19.0)
TSQM- Conveniences Score (n=8) 29.2  (21.4)
TSQM- Global Satisfaction Score -11.6  (31.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments p-value for TSQM Effectiveness Score
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments p-value for TSQM Side-Effects Score
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments p-value for TSQM Convenience Score
Method Wilcoxon signed rank
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Treprostinil
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments p-value for TSQM Global Satisfaction Score
Method Wilcoxon signed rank
Comments [Not Specified]
14.Secondary Outcome
Title Subject Responses to the Patient Impression of Change Questionnaire (Administered at Week 8 Only)
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treprostinil
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 8
Measure Type: Number
Unit of Measure: participants
Symptoms- Much Better 4
Symptoms- Somewhat Better 1
Symptoms- About The Same 1
Symptoms- Somewhat Worse 1
Symptoms- Much Worse 1
Time Spent- Much Less 5
Time Spent- Somewhat Less 2
Time Spent- About The Same 0
Time Spent- Somewhat More 1
Time Spent- Much More 0
Satisfaction- Much More Satisfied 4
Satisfaction- More Satisfied 2
Satisfaction- About The Same 1
Satisfaction- Less Satisfied 0
Satisfaction- Much Less Satisfied 1
Time Frame Adverse Events (AEs) were assessed upon initiation of Remodulin through to the end of study (Week 8)
Adverse Event Reporting Description Since subjects were transitioning from an existing prostacyclin therapy, prostacyclin-class side effects ongoing at Baseline prior to transition were recorded separately on the specific Prostacyclin Side Effects Questionnaire. Events which increased in severity from Baseline were captured and reported as AEs.
 
Arm/Group Title Treprostinil
Hide Arm/Group Description

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

All-Cause Mortality
Treprostinil
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treprostinil
Affected / at Risk (%) # Events
Total   3/8 (37.50%)    
Cardiac disorders   
Fluid overload * 2 [1]  1/8 (12.50%)  1
Right ventricular failure * 2  1/8 (12.50%)  1
Infections and infestations   
central line infection * 1 [2]  1/8 (12.50%)  1
Metabolism and nutrition disorders   
Hyperkalaemia * 2 [2]  1/8 (12.50%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MeDRA 10.0
2
Term from vocabulary, MedDRA 12.0
[1]
One subject was hospitalized for two serious adverse events: fluid overload and right ventricular failure. All events resolved with treatment and subjects continued the study. The investigator judged the event reasonably attributable to treprostinil.
[2]
All events resolved with treatment and subjects continued in the study. The investigator judged the event to be not reasonably attributable to study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treprostinil
Affected / at Risk (%) # Events
Total   8/8 (100.00%)    
Gastrointestinal disorders   
Diarrhoea * 1  6/8 (75.00%)  6
Vomiting * 1  4/8 (50.00%)  5
Nausea * 1  6/8 (75.00%)  6
Retching * 1  1/8 (12.50%)  1
Abdominal distention * 1  1/8 (12.50%)  1
Abdominal pain upper * 1  1/8 (12.50%)  1
Dry mouth * 1  1/8 (12.50%)  1
Flatulence * 1  1/8 (12.50%)  1
General disorders   
Fatigue * 1  5/8 (62.50%)  5
Nasal congestion * 1  2/8 (25.00%)  2
Oedema peripheral * 1  2/8 (25.00%)  2
Chest pain * 1  1/8 (12.50%)  1
Chills * 1  1/8 (12.50%)  1
Catheter site erythema * 1  1/8 (12.50%)  1
Catheter site swelling * 1  1/8 (12.50%)  1
Immune system disorders   
Pyrexia * 1  2/8 (25.00%)  3
Hypersensitivity * 1  1/8 (12.50%)  1
Infections and infestations   
Influenza * 1  2/8 (25.00%)  2
Nasopharyngitis * 1  1/8 (12.50%)  1
Investigations   
International normalised ratio increased * 1  1/8 (12.50%)  1
Metabolism and nutrition disorders   
Fluid retention * 1  1/8 (12.50%)  1
Anorexia * 1  1/8 (12.50%)  1
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  6/8 (75.00%)  9
Arthralgia * 1  3/8 (37.50%)  3
Pain * 1  2/8 (25.00%)  3
Pain in jaw * 1  2/8 (25.00%)  2
Neck pain * 1  1/8 (12.50%)  1
Musculoskeletal pain * 1  1/8 (12.50%)  1
Myalgia * 1  1/8 (12.50%)  1
Back pain * 1  1/8 (12.50%)  1
Hypokalaemia * 1  1/8 (12.50%)  1
Nervous system disorders   
Headache * 1  6/8 (75.00%)  7
Dizziness * 1  2/8 (25.00%)  2
Restless legs syndrome * 1  1/8 (12.50%)  1
Dysarthria * 1  1/8 (12.50%)  1
Somnolence * 1  1/8 (12.50%)  1
Psychiatric disorders   
Insomnia * 1  1/8 (12.50%)  1
Reproductive system and breast disorders   
Productive cough * 1  1/8 (12.50%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea * 1  2/8 (25.00%)  4
Oropharyngeal pain * 1  2/8 (25.00%)  2
Cough * 1  1/8 (12.50%)  1
Rhinorrhoea * 1  1/8 (12.50%)  1
Skin and subcutaneous tissue disorders   
Cold sweat * 1  1/8 (12.50%)  1
Pruritus * 1  1/8 (12.50%)  1
Rash * 1  1/8 (12.50%)  1
Vascular disorders   
Flushing * 1  3/8 (37.50%)  3
Hypotension * 1  2/8 (25.00%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 12.0
The main limitations of this study are the modest sample size and relatively short duration of follow-up.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Any publication of the results of this trial must be consistent with the United Therapeutics publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
Results Point of Contact
Name/Title: Remodulin Program Leader
Organization: United Therapeutics
Phone: (919) 485-8350
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00439946     History of Changes
Other Study ID Numbers: RIV-PH-410
First Submitted: February 22, 2007
First Posted: February 26, 2007
Results First Submitted: March 26, 2013
Results First Posted: July 17, 2013
Last Update Posted: July 17, 2013