Trial Outcomes & Findings for Safety, Efficacy and Treatment Satisfaction in Patients With PAH Rapidly Switched From Epoprostenol to Remodulin (NCT NCT00373360)

NCT ID: NCT00373360

Last Updated: 2013-01-07

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 10 participants
• Primary outcome timeframe: Baseline and Week 8
• Results posted on: 2013-01-07

Participant Flow

Subject participated in this study between July 2007 and January 2008.

All subjects were required to be receiving continuous intravenous epoprostenol therapy for at least three months and at a stable dose for at least thirty days prior to enrollment in this study.

Participant milestones

Measure	Treprostinil Sodium All subjects received active treatment with treprostinil sodium.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treprostinil Sodium n=10 Participants All subjects received active treatment with treprostinil sodium.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	10 participants n=5 Participants
PAH Etiology Idiopathic PAH	7 participants n=5 Participants
PAH Etiology Connective Tissue Disease (CTD)	2 participants n=5 Participants
PAH Etiology Other	1 participants n=5 Participants
World Health Organization (WHO) Functional Classification for PAH Class II	6 participants n=5 Participants
World Health Organization (WHO) Functional Classification for PAH Class III	4 participants n=5 Participants
Six minute walk distance	447.7 meters n=5 Participants
Epoprostenol dose	27.15 ng/kg/min n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: As this was a small open label study, the statistics applied to the results were descriptive. For all efficacy endpoints, data obtained from study assessments during the treatment phase were compared to Baseline. assessments

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in the Distance Transversed During the 6 Minute Walk Test From Baseline to Week 8.	-2.2 meters Standard Deviation 34.8

SECONDARY outcome

Timeframe: Baseline and Week 8

The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6-minute walk test. The Borg dyspnea score was assessed immediately following the 6-minute walk test. Scores ranged from 0 (for no shortness of breath) to 10 (for greatest shortness of breath ever experienced).

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Borg Dyspnea Score Immediately After Six Minute Walk Test From Baseline to Week 8	1.56 units on a scale Standard Deviation 0.98

SECONDARY outcome

Timeframe: Baseline and Week 8

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

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

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

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

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in World Health Organization (WHO) Functional Classification of PAH From Baseline to Week 8 Improved	11 percentage of participants
Change in World Health Organization (WHO) Functional Classification of PAH From Baseline to Week 8 No Change	89 percentage of participants
Change in World Health Organization (WHO) Functional Classification of PAH From Baseline to Week 8 Worsened	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

The presence or absence of dyspnea was documented. If present, the intensity of dyspnea was rated mild, moderate, or severe.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Symptoms of Dyspnea From Baseline to Week 8 Improved	22 percentage of participants
Change in Symptoms of Dyspnea From Baseline to Week 8 No Change	33 percentage of participants
Change in Symptoms of Dyspnea From Baseline to Week 8 Worsened	44 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 8

The presence or absence of edema was documented. If present, the intensity of edema was rated mild, moderate, or severe.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Symptoms of Edema From Baseline to Week 8 Improved	22 percentage of participants
Change in Symptoms of Edema From Baseline to Week 8 No Change	56 percentage of participants
Change in Symptoms of Edema From Baseline to Week 8 Worsened	22 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

The presence or absence of orthopnea was documented. If present, the intensity of orthopnea was rated mild, moderate, or severe.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Symptoms of Orthopnea From Baseline to Week 8 Improved	22 percentage of participants
Change in Symptoms of Orthopnea From Baseline to Week 8 No Change	78 percentage of participants
Change in Symptoms of Orthopnea From Baseline to Week 8 Worsened	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

The presence or absence of dizziness was documented. If present, the intensity of dizziness was rated mild, moderate, or severe.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Symptoms of Dizziness From Baseline to Week 8 Improved	11 percentage of participants
Change in Symptoms of Dizziness From Baseline to Week 8 No Change	89 percentage of participants
Change in Symptoms of Dizziness From Baseline to Week 8 Worsened	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

The presence or absence of fatigue was documented. If present, the intensity of fatigue was rated mild, moderate, or severe.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Symptoms of Fatigue From Baseline to Week 8 Improved	22 percentage of participants
Change in Symptoms of Fatigue From Baseline to Week 8 No Change	67 percentage of participants
Change in Symptoms of Fatigue From Baseline to Week 8 Worsened	11 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

The presence or absence of syncope was documented. If present, the intensity of syncope was rated mild, moderate, or severe.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Symptoms of Syncope From Baseline to Week 8 Improved	0 percentage of participants
Change in Symptoms of Syncope From Baseline to Week 8 No Change	100 percentage of participants
Change in Symptoms of Syncope From Baseline to Week 8 Worsened	0 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Symptoms of Chest Pain From Baseline to Week 8 Worsened	11 percentage of participants
Change in Symptoms of Chest Pain From Baseline to Week 8 Improved	0 percentage of participants
Change in Symptoms of Chest Pain From Baseline to Week 8 No Change	89 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 8

The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Effectiveness Score on Treatment Satisfaction Scale From Baseline to Week 8 Effectiveness Score at Baseline	71.6 units on a scale Standard Deviation 29.2
Change in Effectiveness Score on Treatment Satisfaction Scale From Baseline to Week 8 Effectiveness Score at Week 8	82.7 units on a scale Standard Deviation 23.1

SECONDARY outcome

Timeframe: Baseline and Week 8

The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Side-Effects Score on Treatment Satisfaction Scale From Baseline to Week 8 Side Effects Score at Baseline	71.5 units on a scale Standard Deviation 14.4
Change in Side-Effects Score on Treatment Satisfaction Scale From Baseline to Week 8 Side Effects Score at Week 8	84.7 units on a scale Standard Deviation 12.1

SECONDARY outcome

Timeframe: Baseline and Week 8

The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Convenience Score on Treatment Satisfaction Scale From Baseline to Week 8 Convenience Score at Baseline	59.9 units on a scale Standard Deviation 14.4
Change in Convenience Score on Treatment Satisfaction Scale From Baseline to Week 8 Convenience Score at Week 8	90.7 units on a scale Standard Deviation 10.8

SECONDARY outcome

Timeframe: Baseline and Week 8

The Treatment Satisfaction Questionnaire for Medication (TSQM) is a validated instrument that measures four major dimensions of patient satisfaction with medications: effectiveness, side effects, convenience, and global satisfaction. TSQM Scale scores are computed by adding the items loading on each factor. The lowest possible score is subtracted from this composite score and divided by the greatest possible score minus the lowest possible score. This provided a transformed score between 0 and 1 that should be multiplied by 100 (scale 0-100). A low score indicates low satisfaction and a high score indicates high satisfaction with treatment.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Global Satisfaction Score on Treatment Satisfaction Scale From Baseline to Week 8 Global Satisfaction Score at Baseline	84.1 units on a scale Standard Deviation 15.1
Change in Global Satisfaction Score on Treatment Satisfaction Scale From Baseline to Week 8 Global Satisfaction Score at Week 8	92.1 units on a scale Standard Deviation 14.0

SECONDARY outcome

Timeframe: Baseline and Week 8

The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a health related quality of life instrument specific to PAH. The total score can range from 0 -75; the higher the score, the worse the outcome.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Score on Quality of Life Questionnaire From Baseline to Week 8 CAMPHOR score at Baseline	18.9 units on a scale Standard Deviation 12.5
Change in Total Score on Quality of Life Questionnaire From Baseline to Week 8 CAMPHOR score at Week 8	12.9 units on a scale Standard Deviation 10.8

SECONDARY outcome

Timeframe: Baseline and Week 8

Subjects were asked to compare their symptoms of PAH as compared to 8 weeks prior and rate as much better, somewhat better, about the same, somewhat worse, or much worse.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Patient Impression of Change in Symptoms of PAH From Baseline to Week 8 Much better	5 participants
Change in Patient Impression of Change in Symptoms of PAH From Baseline to Week 8 Somewhat better	1 participants
Change in Patient Impression of Change in Symptoms of PAH From Baseline to Week 8 About the same	3 participants
Change in Patient Impression of Change in Symptoms of PAH From Baseline to Week 8 Somewhat worse	0 participants
Change in Patient Impression of Change in Symptoms of PAH From Baseline to Week 8 Much worse	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Subjects were asked to compare their previous experience with Flolan and rate how much time was spent dealing with intravenous Remodulin therapy as much less, somewhat less, about the same, somewhat more, or much more.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Patient Impression of Change on Time Spent Dealing With Therapy From Baseline to Week 8 Much less	8 participants
Change in Patient Impression of Change on Time Spent Dealing With Therapy From Baseline to Week 8 Somewhat Less	0 participants
Change in Patient Impression of Change on Time Spent Dealing With Therapy From Baseline to Week 8 About the same	1 participants
Change in Patient Impression of Change on Time Spent Dealing With Therapy From Baseline to Week 8 Somewhat more	0 participants
Change in Patient Impression of Change on Time Spent Dealing With Therapy From Baseline to Week 8 Much more	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Subjects were asked to compare their previous experience with Flolan and rate satisfaction with intravenous Remodulin therapy over the past two weeks as much more satisfied, more satisfied, about the same, less satisfied, or much less satisfied.

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Patient Impression of Change of Satisfaction With Therapy From Baseline to Week 8 Much more satisfied	7 participants
Change in Patient Impression of Change of Satisfaction With Therapy From Baseline to Week 8 More satisfied	2 participants
Change in Patient Impression of Change of Satisfaction With Therapy From Baseline to Week 8 About the same	0 participants
Change in Patient Impression of Change of Satisfaction With Therapy From Baseline to Week 8 Less satisfied	0 participants
Change in Patient Impression of Change of Satisfaction With Therapy From Baseline to Week 8 Much less satisfied	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Weekly Time Spent to Gather/Set-up Materials Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time to gather/set up epoprostenol at Baseline	34.9 minutes Standard Deviation 28.7
Change in Total Weekly Time Spent to Gather/Set-up Materials Associated With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time to gather/set up Remodulin at Week 8	27.0 minutes Standard Deviation 28.7

SECONDARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Weekly Time Spent to Connect Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time spent to connect epoprostenol at Baseline	23.2 minutes Standard Deviation 14.4
Change in Total Weekly Time Spent to Connect Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time spent to connect Remodulin at Week 8	18.7 minutes Standard Deviation 13.9

SECONDARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Weekly Time Spent to Change Dressing With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time to change dressing with Remdoluin at Wk 8	28.6 minutes Standard Deviation 25.8
Change in Total Weekly Time Spent to Change Dressing With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time to change dressing with epoprostenol at BL	31.4 minutes Standard Deviation 14.2

SECONDARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Weekly Time Spent to Prepare Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time to prepare epoprostenol at Baseline	109.0 minutes Standard Deviation 61.0
Change in Total Weekly Time Spent to Prepare Drug With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Time to prepare Remodulin at Week 8	47.8 minutes Standard Deviation 31.6

SECONDARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Number of Times Daily Required to Disconnect Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Disconnect pump at Baseline (epoprostenol)	7.7 number of times per day Standard Deviation 5.3
Change in Total Number of Times Daily Required to Disconnect Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Disconnect pump at Wk 8 (Remodulin)	4.1 number of times per day Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Number of Times Daily Required to Check Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Check pump at Baseline (epoprostenol)	19.2 number of times per day Standard Deviation 11.5
Change in Total Number of Times Daily Required to Check Infusion Pump With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Check pump at Week 8 (Remodulin)	12.2 number of times per day Standard Deviation 8.9

SECONDARY outcome

Timeframe: Baseline and Week 8

Outcome measures

Measure	Treprostinil Sodium n=9 Participants All subjects received active treatment with treprostinil sodium.
Change in Total Number of Times Daily Infusion Pump Alarms With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Daily alarms at Baseline (epoprostenol)	2.4 number of times per day Standard Deviation 3.3
Change in Total Number of Times Daily Infusion Pump Alarms With Intravenous Remodulin Therapy Compared to Same Activities With Intravenous Epoprostenol Daily alarms at Week 8 (Remodulin)	0.8 number of times per day Standard Deviation 1.1

Adverse Events

Treprostinil Sodium

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treprostinil Sodium n=10 participants at risk All subjects received active treatment with treprostinil sodium.
Gastrointestinal disorders Gastroenteritis	20.0% 2/10 • Number of events 2

Other adverse events

Measure	Treprostinil Sodium n=10 participants at risk All subjects received active treatment with treprostinil sodium.
Musculoskeletal and connective tissue disorders Pain in extremity	50.0% 5/10 • Number of events 7
General disorders Headache	20.0% 2/10 • Number of events 2
Nervous system disorders Restless Leg Syndrome	20.0% 2/10 • Number of events 2
Cardiac disorders Atrial fibrillation	10.0% 1/10 • Number of events 1
Gastrointestinal disorders Diarrhea	10.0% 1/10 • Number of events 1
Musculoskeletal and connective tissue disorders Hand fracture	10.0% 1/10 • Number of events 1
Skin and subcutaneous tissue disorders Injection site erythema	10.0% 1/10 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle spasms	10.0% 1/10 • Number of events 1
Gastrointestinal disorders Nausea	10.0% 1/10 • Number of events 1
Vascular disorders Peripheral edema	10.0% 1/10 • Number of events 1
Respiratory, thoracic and mediastinal disorders Sinus congestion	10.0% 1/10 • Number of events 1
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	10.0% 1/10 • Number of events 1
Gastrointestinal disorders Vomiting	10.0% 1/10 • Number of events 1
Skin and subcutaneous tissue disorders catheter site inflammation	10.0% 1/10 • Number of events 1

Additional Information

Rex Mauthe; Senior Director, Regulatory Affairs

United Therapeutics Corporation

Phone: 919-485-8350

Email: rmauthe@unither.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60