Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Digital Ischemic Lesions in Scleroderma Treated With Oral Treprostinil Diethanolamine (DISTOL-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00775463
Recruitment Status : Completed
First Posted : October 20, 2008
Results First Posted : March 17, 2014
Last Update Posted : March 17, 2014
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Systemic Sclerosis
Scleroderma
Interventions Drug: treprostinil diethanolamine
Drug: placebo
Enrollment 148
Recruitment Details Subjects were recruited across 32 clinical trial sites in the US, Canada and UK experienced in the treatment of systemic sclerosis (SSc) and capable of conducting the trial according to ICH GCP guidance. Subjects were recruited between April 2009 and October 2010.
Pre-assignment Details  
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description All subjects who recieved at least one dose of study drug. All subejcts who recieved at least one dose of study drug. One subject in the treprostinil diethanolamine treatment group was randomized, withdrew consent and exited the study prior to taking any study medication and is not included in the analysis summary.
Period Title: Overall Study
Started 76 72
Completed 65 59
Not Completed 11 13
Reason Not Completed
Withdrawal by Subject             0             1
Adverse Event             7             9
Protocol Violation             2             2
Lost to Follow-up             1             0
Lack of Efficacy             1             1
Arm/Group Title Placebo Treprostinil Diethanolamine Total
Hide Arm/Group Description intent to treat population intent to treat population Total of all reporting groups
Overall Number of Baseline Participants 76 71 147
Hide Baseline Analysis Population Description
Baseline demographics and characteristics were summarized for subjects who received at least one dose of study drug. One subject in the treprostinil diethanolamine treatment group was randomized, withdrew consent and exited the study prior to taking any study medication and is not included in the summary.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 76 participants 71 participants 147 participants
47.8
(20 to 74)
49.8
(19 to 82)
48.8
(19 to 82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants 71 participants 147 participants
Female
55
  72.4%
54
  76.1%
109
  74.1%
Male
21
  27.6%
17
  23.9%
38
  25.9%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 76 participants 71 participants 147 participants
Asian 3 4 7
Native Hawaiian or Other Pacific Islander 0 1 1
Black or African American 10 7 17
White 62 59 121
Unknown or Not Reported 1 1 2
[1]
Measure Description: Note: A Subject can be included in more than one race category.
SSc Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 76 participants 71 participants 147 participants
Limited 55 40 95
Diffuse 21 31 52
Years since SSc diagnosis  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 76 participants 71 participants 147 participants
10.7
(0 to 30)
10.3
(0 to 35)
10.5
(0 to 35)
1.Primary Outcome
Title Net Ulcer Burden
Hide Description Net ulcer burden was defined as the number of “new” or “active” digital ulcers (DU), plus the number of “indeterminate” DUs at that assessment that have previously been classified as either “active” or “new” at any earlier assessment during the study. A DU was defined as an area with visually discernable depth and a loss of continuity of epithelial coverage, which could be denuded or covered by a scab or necrotic tissue. If denuded, the DU was pronounced “active.” If denudation could not be judged because of the presence of scab or necrotic tissue, DU presenting with features, including underlying pain, based on Investigator clinical judgment to be consistent with loss of epithelialization, epidermis, or dermis, and requiring treatment were designated as “active.” Otherwise, the DU was pronounced “indeterminate.” Only DUs distal to the proximal interphalangeal joints, volar to the equator of the finger, not localized in creases and vascular in origin were assessed.
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change.
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71
Median (Inter-Quartile Range)
Unit of Measure: ulcers
Baseline
1.0
(1.0 to 2.0)
2.0
(1.0 to 2.0)
Change at Week 20
0.0
(-1.0 to 1.0)
-1.0
(-1.0 to 0.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments A Cochran-Mantel Haenszel mean score test was used on the standardized reverse mid-ranks (overall reverse ranks divided by the number of ranks +1, or modified ridit scores; largely negative changes had ranks near 1 and largely positive changes had ranks near 0)of the residuals from an ordinary least squares regression with change in net ulcer burden at Week 20 as a linear function of Baseline PDEI or prostacyclin use (binary variable:Yes/No) and net ulcer burden at Baseline(continuous variable).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.20
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.0 to 0.0
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Digital Ulcer Pain VAS
Hide Description Digital ulcer pain was rated on a 100-mm VAS on which subjects were asked to rate their average overall hand pain during the last week. The recorded value was divided by 10, with values ranging from 0.0 (no pain) to 10.0 (unbearable pain), expressed to one decimal.
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 70
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Baseline
4.85
(2.75 to 6.75)
6.00
(2.80 to 7.70)
Change at Week 20
-1.05
(-3.20 to 0.10)
-1.45
(-4.60 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments The difference between treatment groups for the change from Baseline was tested using the Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments Analyses of secondary endpoints were descriptive in nature, no adjustments for multiplicity were made. P-values are for the purpose of describing the random imbalance between treatment groups and not to test formal hypotheses.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-1.40 to 0.40
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Patient Global Assessment of Digital Ulcer Severity VAS
Hide Description

Patients rated their global impression of digital ulcer severity on a 15-cm VAS from scaled 0 (no disease activity) to 100 (very severe disease).

The term “severity” was used to measure the extent of disease activity and associated disability or discomfort the patient experienced during the indicated time period.

Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 70
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Baseline
57.0
(29.3 to 79.7)
67.0
(34.7 to 78.0)
Change at Week 20
-24.0
(-43.0 to 0.0)
-24.3
(-63.3 to -3.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments The VAS-global assessments were recorded in centimeters, with possible values ranging from 0.0 to 15.0. The recorded value was divided by 15, then multiplied by 100 to convert it to the VAS-Global scale, with values ranging from 0 (no disease activity) to 100 (very severe disease). The difference between treatment groups for the change from Baseline was tested using the Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments Analyses of secondary endpoints were descriptive in nature, no adjustments for multiplicity were made. P-values are for the purpose of describing the random imbalance between treatment groups and not to test formal hypotheses.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value -9.3
Confidence Interval (2-Sided) 95%
-21.3 to 2.7
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Physician Global Assessment of Digital Ulcer Severity VAS
Hide Description

Physicians rated their global impression of digital ulcer severity on a 15-cm VAS from scaled 0 (no disease activity) to 100 (very severe disease).

The term “severity” was used to measure the extent of disease activity and associated disability or discomfort the patient experienced during the indicated time period.

Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 70
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Baseline
44.7
(26.0 to 63.3)
47.3
(31.3 to 66.7)
Change at Week 20
-13.3
(-31.3 to -1.3)
-26.7
(-43.3 to -5.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments The VAS-global assessments were recorded in centimeters, with possible values ranging from 0.0 to 15.0. The recorded value was divided by 15, then multiplied by 100 to convert it to the VAS-Global scale, with values ranging from 0 (no disease activity) to 100 (very severe disease). The difference between treatment groups for the change from Baseline was tested using the Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments Analyses of secondary endpoints were descriptive in nature, no adjustments for multiplicity were made. P-values are for the purpose of describing the random imbalance between treatment groups and not to test formal hypotheses.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value -9.3
Confidence Interval (2-Sided) 95%
-18.0 to 0.0
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Cochin Hand Function Scale (CHFS)
Hide Description The CHFS has been demonstrated as a reliable and valid assessment of hand function at the activity level in persons with SSc. It is comprised of 18 questions with possible integer responses of 0 (without difficulty) to 5 (impossible). The CHFS Score is simply the sum of all 18 questions, divided by the number of questions actually answered, multiplied by 18. At least 10 of the 18 questions must have been answered in order for CHFS to be calculated. Therefore, CHFS Score values can range from 0 (least limitation) to 90 (most limitation). A higher score indicates more difficulty in hand function or greater disability.
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71
Median (95% Confidence Interval)
Unit of Measure: units on a scale
Baseline
18.5
(5.0 to 29.5)
24.0
(11.0 to 37.0)
Week 20
19.0
(4.0 to 33.5)
21.0
(8.0 to 35.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments The difference between treatment groups for the change from Baseline in CHFS Score were tested using the Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments Analyses of secondary endpoints were descriptive in nature, no adjustments for multiplicity were made. P-values are for the purpose of describing the random imbalance between treatment groups and not to test formal hypotheses.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-4.0 to 2.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Scleroderma Health Assessment Questionnaire (SHAQ)
Hide Description The SHAQ is a patient self-administered instrument which has been previously validated in SSc and demonstrates meaningful clinical changes in the course of the disease over time. It is comprised of a 20 question instrument pertaining to specific activities with possible integer responses of 0 (without any difficulty) to 3 (unable to do), and five additional scleroderma-specific visual analog scale (VAS) domains (Overall Disease Activity, Raynaud’s Phenomenon, Finger Ulcers, Breathing, and Intestinal Problems) with possible values ranging from 0.0 to 15.0. The 20 questions are divided into eight domains. A mean score is calculated for each domain ranging from 0 to 3. A composite HAQ DI score is calculated by dividing the summed domain scores by the number of domains answered. The composite score is reported, falling between 0 and 3 on an ordinal scale. The scores are interpreted as 0 (no impairment in function) to 3 (maximal impairment of function).
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Dressing & Grooming Score: Baseline (76/71)
0.50
(0.00 to 1.00)
1.00
(0.50 to 1.50)
Dressing&Grooming Score:Change at Week 20
0.00
(0.00 to 0.00)
0.00
(-0.50 to 0.00)
Arising Score: Baseline (76/71)
0.00
(0.00 to 1.00)
0.00
(0.00 to 1.00)
Arising Score: Change at Week 20
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
Eating Score: Baseline (76/71)
0.67
(0.00 to 1.00)
0.67
(0.33 to 1.00)
Eating Score: Change at Week 20
0.00
(-1.17 to 0.08)
0.00
(-0.33 to 0.17)
Walking Score: Baseline (76/71)
0.00
(0.00 to 0.50)
0.00
(0.00 to 0.50)
Walking Score: Change at Week 20
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
Hygiene Score: Baseline (76/68)
0.00
(0.00 to 0.67)
0.33
(0.00 to 0.67)
Hygiene Score: Change at Week 20
0.00
(0.00 to 0.33)
0.00
(0.00 to 0.33)
Reach Score: Baseline (76/68)
0.00
(0.00 to 1.00)
0.50
(0.00 to 1.00)
Reach Score: Change at Week 20
0.00
(0.00 to 0.00)
0.00
(0.00 to 0.00)
Grip Score: Baseline (76/68)
0.33
(0.00 to 0.67)
0.33
(0.17 to 1.00)
Grip Score: Change at Week 20
0.00
(0.00 to 0.33)
0.00
(-0.33 to 0.00)
Activity Score: Baseline (76/68)
0.33
(0.00 to 1.00)
0.67
(0.00 to 1.00)
Activity Score: Change at Week 20
0.00
(0.00 to 0.33)
0.00
(0.00 to 0.17)
HAQ Aggregate Score: Baseline (76/68)
0.34
(0.10 to 0.77)
0.53
(0.26 to 0.81)
HAQ Aggregate Score: Change at Week 20
0.00
(-0.07 to 0.13)
-0.03
(-0.16 to 0.12)
Hand Function Aggregate Score: Baseline (76/68)
0.39
(0.11 to 0.69)
0.56
(0.28 to 0.86)
Hand Function Aggregate Score: Change at Week 20
0.00
(-0.06 to 0.17)
0.00
(-0.22 to 0.11)
Raynaud's Phenomenon VAS Score: Baseline (75/71)
0.12
(0.00 to 0.64)
0.18
(0.02 to 0.80)
Raynaud's Phenomenon VAS Score: Change at Week 20
0.00
(-0.14 to 0.08)
0.00
(-0.14 to 0.14)
Intestinal Problems VAS Score: Baseline (75/70)
0.20
(0.00 to 0.70)
0.11
(0.02 to 0.62)
Intestinal Problems VAS Score: Change at Week 20
0.00
(-0.10 to 0.24)
0.11
(-0.02 to 0.72)
Digital Ulcer VAS Score: Baseline (76/71)
1.43
(0.49 to 2.09)
1.50
(0.68 to 2.28)
Digital Ulcer VAS Score: Change at Week 20
-0.34
(-0.92 to 0.00)
-0.56
(-1.36 to 0.00)
Breathing Problems VAS Score: Baseline (76/71)
1.54
(0.95 to 2.31)
2.16
(0.96 to 2.54)
Breathing Problems VAS Score: Change at Week 20
-0.50
(-1.15 to 0.00)
-0.84
(-2.14 to -0.20)
Pain VAS Score: Baseline (76/69)
1.27
(0.57 to 1.91)
1.54
(0.54 to 2.16)
Pain VAS Score: Change at Week 20
-0.26
(-0.93 to 0.11)
-0.34
(-1.44 to 0.00)
Overall Disease VAS Score: Baseline (76/71)
1.22
(0.67 to 1.87)
1.52
(0.74 to 2.12)
Overall Disease VAS Score: Change at Week 20
-0.18
(-0.60 to 0.04)
-0.32
(-1.00 to 0.10)
7.Secondary Outcome
Title Modified Rodnan Skin Score (mRSS)
Hide Description The skin thickening was assessed by the Investigator in 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (bilaterally) and face, chest, and abdomen (singly). Each area was scored 0–3; 0 representing normal skin and 3 being severe thickening. The mRSS was the sum of the individual skin assessment scores: possible range of 0-51; 0 (no thickening) to 51 (severe thickening in all 17 areas) .
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Baseline
6.0
(3.0 to 12.0)
8.0
(5.0 to 14.0)
Week 20
6.0
(3.0 to 12.0)
6.0
(3.0 to 15.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments he difference between treatment groups for the change from Baseline and at Week 20 in the mRSS was tested using the Wilcoxon rank-sum test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
0.0 to 1.0
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Short-Form McGill Pain Questionnaire
Hide Description The SF-MPQ assessment has three component scores: the pain rating index (PRI), a pain visual analogue numerical scale (Pain VAS) and the present pain intensity (PPI). PRI is calculated by summing the responses (0=None to 3=Severe) to the 15 questions describing pain during the previous week and rated on an intensity scale as 0= none, 1= mild, 2= moderate or 3= severe and has possible values ranging from 0 to 45. The Pain VAS is a 100 mm VAS on which subjects were asked to rate pain during the previous week with values ranging from no pain (0.0) to worst possible pain (10.0). The PPI rated pain on a 6-point category scale from 0 (no pain) to 5 (excruciating pain).
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 74 68
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Total Pain Rating Index Score Change at Week 20
-4.0
(-8.0 to 1.0)
-3.0
(-12.0 to 0.0)
Pain VAS Score Change at Week 20
-0.6
(-2.9 to 0.3)
-1.1
(-4.4 to 0.2)
Present Pain Intensity Score Change at Week 20
0.0
(-1.0 to 0.0)
-1.0
(-1.0 to 0.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments P value for Total Pain Rating Index Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.54
Comments P value for Total Pain Rating Index Score
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-3.0 to 2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments P value for Pain VAS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments P value for Pain VAS
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Ef
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.6 to 0.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Treprostinil Diethanolamine
Comments P value for Total Pain Rating Index Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments P value for Total Pain Rating Index Score
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann Estimate of Treatment Eff
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.0 to 0.0
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Patient Impression of Change (PIC) Questionnaire
Hide Description The PIC questionnaire consisted of three Likert items that asked the subject to rate changes in their digital ulcer, Raynaud’s phenomenon and disease status since their last visit on a seven-level scale (very much improved, much improved, somewhat improved, same, somewhat worse, much worse and very much worse).
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo- Digital Ulcer Response Treprostinil Diethanolamine- Digital Ulcer Response Placebo- Raynaud's Phenomenon Response Treprostinil Diethanolamine- Raynaud's Phenomenon Response Placebo- Overall Disease Status Response Treprostinil Diethanolamine- Overall Disease Status Response
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71 76 71 76 71
Measure Type: Number
Unit of Measure: participants
Very Much Improved 5 9 0 3 0 3
Much Improved 11 15 4 12 5 17
Somewhat Improved 20 14 12 20 22 13
Same 24 21 40 30 30 27
Somewhat Worse 14 8 17 4 18 10
Much Worse 1 3 1 1 0 0
Very Much Worse 1 1 2 1 1 1
10.Secondary Outcome
Title Short Form 36
Hide Description Change in patient quality of life was measured by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), a self-administered questionnaire covering eight areas: physical function, physical role, bodily pain, general health, vitality, social function, emotional role, and mental health. For each area, the score range from 0 (poorer health status) to 100 (better health status). The SF-36 is one of the most widely used and validated instruments to assess quality of life in patients with systemic illnesses. A decrease (negative change) in a domain score corresponds to deterioration.
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population is all subjects that received at least one dose of study drug. Subjects were counted in the assigned group regardless of the actual treatment given. Missing values imputed by carrying last observation forward or assigning value equalling overall poorest relative change. Excluded subjects without a Baseline observation
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
Physical Component: Baseline
55.0
(39.5 to 67.5)
50.7
(35.1 to 62.9)
Physical Component: Change at Week 20
2.8
(-5.3 to 10.9)
3.8
(-2.1 to 10.3)
Physical Functioning: Baseline
62.5
(30.0 to 80.0)
60.0
(35.0 to 75.0)
Physical Functioning: Change at Week 20
0.0
(-5.0 to 10.0)
0.0
(-10.0 to 10.0)
Role-Physical: Baseline
54.4
(37.5 to 72.5)
50.0
(25.0 to 70.0)
Role-Physical: Change at Week 20
0.0
(-10.0 to 17.5)
0.0
(0.0 to 22.5)
Bodily Pain: Baseline
57.5
(33.8 to 67.5)
45.0
(32.5 to 75.0)
Bodily Pain: Change at Week 20
10.0
(-5.0 to 21.3)
10.0
(-2.5 to 22.5)
General Health: Baseline
42.0
(34.0 to 65.0)
45.0
(30.0 to 63.0)
General Health: Change at Week 20
0.0
(-9.5 to 5.0)
0.0
(-5.0 to 6.0)
Mental Component: Baseline
68.3
(54.1 to 77.4)
64.2
(49.2 to 76.1)
Mental Component: Change at Week 20
2.6
(-8.6 to 11.0)
4.0
(-4.0 to 15.7)
Vitality: Baseline (75/71)
50.0
(31.3 to 62.5)
43.8
(25.0 to 61.3)
Vitality: Change at Week 20
0.0
(-6.3 to 7.5)
1.3
(-6.3 to 17.5)
Social Functioning: Baseline
72.5
(50.0 to 87.5)
62.5
(50.0 to 85.0)
Social Functioning: Change at Week 20
0.0
(-12.5 to 13.8)
10.0
(0.0 to 22.5)
Role-Emotional: Baseline
70.0
(60.8 to 95.0)
80.0
(50.0 to 100.0)
Role-Emotional: Change at Week 20
0.0
(-5.8 to 11.7)
0.0
(-1.7 to 13.3)
Mental Health: Baseline (75/71)
69.0
(52.0 to 84.0)
64.0
(54.0 to 79.0)
Mental Health: Change at Week 20
2.0
(-6.0 to 11.0)
3.0
(-5.0 to 16.0)
11.Secondary Outcome
Title Time to Ulcer Healing- Percentage of Subjects With Complete Healing
Hide Description A subject was counted as having all ulcers completely healed at the earliest assessment for which all ulcers are designated as “healed” and no new ulcers appeared for the remainder of the trial.
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71
Measure Type: Number
Unit of Measure: percentage of participants
Cardinal Ulcer Healed 61 62
All Ulcers Healed 41 49
12.Secondary Outcome
Title Time to Ulcer Healing
Hide Description A subject was counted as having all ulcers completely healed at the earliest assessment for which all ulcers are designated as “healed” and no new ulcers appeared for the remainder of the trial. The time to complete healing of all ulcers were calculated as the number of days from randomization to the date of these respective assessments, provided that complete healing was achieved during the study.
Time Frame Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description:
Placebo intent to treat population
Treprostinil diethanolamine intent to treat population
Overall Number of Participants Analyzed 76 71
Mean (Standard Deviation)
Unit of Measure: days
Time to Cardinal Ulcer Healing 83.2  (37.9) 76.3  (35)
Time to All Ulcers Healed 96.7  (39.7) 90.2  (35.6)
Time Frame 20 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Treprostinil Diethanolamine
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Placebo Treprostinil Diethanolamine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Treprostinil Diethanolamine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/76 (5.26%)      9/71 (12.68%)    
Blood and lymphatic system disorders     
Anaemia *  0/76 (0.00%)  0 1/71 (1.41%)  1
Cardiac disorders     
Tachyarrhythmia *  0/76 (0.00%)  0 1/71 (1.41%)  1
Gastrointestinal disorders     
Vomiting *  1/76 (1.32%)  1 1/71 (1.41%)  1
Constipation *  0/76 (0.00%)  0 1/71 (1.41%)  1
Erosive oesophagitis *  0/76 (0.00%)  0 1/71 (1.41%)  1
Gastric ulcer haemorrhage *  0/76 (0.00%)  0 1/71 (1.41%)  1
Gastrointestinal haemorrhage *  0/76 (0.00%)  0 1/71 (1.41%)  1
Nausea *  0/76 (0.00%)  0 1/71 (1.41%)  1
General disorders     
Device dislocation *  0/76 (0.00%)  0 1/71 (1.41%)  1
Hepatobiliary disorders     
Cholecystitis acute *  0/76 (0.00%)  0 1/71 (1.41%)  1
Infections and infestations     
Pneumonia *  1/76 (1.32%)  1 1/71 (1.41%)  1
Cellulitis *  1/76 (1.32%)  1 0/71 (0.00%)  0
Gastroenteritis *  0/76 (0.00%)  0 1/71 (1.41%)  1
Metabolism and nutrition disorders     
Hypokalaemia *  0/76 (0.00%)  0 1/71 (1.41%)  1
Musculoskeletal and connective tissue disorders     
Scleroderma *  1/76 (1.32%)  1 0/71 (0.00%)  0
Nervous system disorders     
Syncope *  0/76 (0.00%)  0 1/71 (1.41%)  1
Respiratory, thoracic and mediastinal disorders     
Pneumothorax *  0/76 (0.00%)  0 2/71 (2.82%)  4
Dyspnoea *  0/76 (0.00%)  0 1/71 (1.41%)  1
Hypoxia *  0/76 (0.00%)  0 1/71 (1.41%)  1
Pulmonary embolism *  1/76 (1.32%)  1 0/71 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin ulcer *  0/76 (0.00%)  0 1/71 (1.41%)  1
Vascular disorders     
Hypotension *  0/76 (0.00%)  0 1/71 (1.41%)  1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Treprostinil Diethanolamine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   74/76 (97.37%)      71/71 (100.00%)    
Gastrointestinal disorders     
Diarrhoea *  16/76 (21.05%)  21 40/71 (56.34%)  48
Vomiting *  4/76 (5.26%)  5 12/71 (16.90%)  18
Abdominal discomfort *  1/76 (1.32%)  1 10/71 (14.08%)  11
Gastrooesophageal reflux disease *  7/76 (9.21%)  7 4/71 (5.63%)  4
Abdominal distension *  5/76 (6.58%)  6 4/71 (5.63%)  4
Constipation *  3/76 (3.95%)  3 5/71 (7.04%)  5
Abdominal pain *  3/76 (3.95%)  4 5/71 (7.04%)  5
Dyspepsia *  4/76 (5.26%)  4 2/71 (2.82%)  3
Abdominal pain upper *  2/76 (2.63%)  2 4/71 (5.63%)  5
Nausea *  14/76 (18.42%)  16 42/71 (59.15%)  49
General disorders     
Fatigue *  15/76 (19.74%)  15 16/71 (22.54%)  18
Oedema peripheral *  11/76 (14.47%)  12 9/71 (12.68%)  10
Pain *  1/76 (1.32%)  1 12/71 (16.90%)  18
Chest pain *  4/76 (5.26%)  4 1/71 (1.41%)  1
Infections and infestations     
Localised infection *  5/76 (6.58%)  5 5/71 (7.04%)  5
Metabolism and nutrition disorders     
Decreased appetite *  4/76 (5.26%)  4 8/71 (11.27%)  8
Musculoskeletal and connective tissue disorders     
Pain in extremity *  12/76 (15.79%)  16 12/71 (16.90%)  13
Pain in jaw *  4/76 (5.26%)  5 17/71 (23.94%)  20
Arthralgia *  9/76 (11.84%)  9 11/71 (15.49%)  11
Myalgia *  5/76 (6.58%)  6 11/71 (15.49%)  13
Muscle spasms *  4/76 (5.26%)  4 11/71 (15.49%)  11
Back pain *  6/76 (7.89%)  7 8/71 (11.27%)  9
Nervous system disorders     
Headache *  32/76 (42.11%)  46 52/71 (73.24%)  71
Dizziness *  8/76 (10.53%)  9 8/71 (11.27%)  9
Migraine *  2/76 (2.63%)  2 4/71 (5.63%)  6
Paraesthesia *  1/76 (1.32%)  1 5/71 (7.04%)  6
Psychiatric disorders     
Insomnia *  4/76 (5.26%)  4 5/71 (7.04%)  5
Renal and urinary disorders     
Urinary tract infection *  4/76 (5.26%)  5 4/71 (5.63%)  4
Respiratory, thoracic and mediastinal disorders     
Dyspnoea *  6/76 (7.89%)  7 5/71 (7.04%)  6
Nasopharyngitis *  8/76 (10.53%)  8 3/71 (4.23%)  3
Upper respiratory tract infection *  7/76 (9.21%)  8 3/71 (4.23%)  3
Oropharyngeal pain *  6/76 (7.89%)  7 2/71 (2.82%)  3
Cough *  6/76 (7.89%)  6 2/71 (2.82%)  2
Skin and subcutaneous tissue disorders     
Infected skin ulcer *  10/76 (13.16%)  13 13/71 (18.31%)  16
Skin ulcer *  4/76 (5.26%)  7 5/71 (7.04%)  6
Rash *  4/76 (5.26%)  5 6/71 (8.45%)  6
Vascular disorders     
Flushing *  3/76 (3.95%)  3 17/71 (23.94%)  19
Peripheral ischaemia *  4/76 (5.26%)  4 0/71 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
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.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Oral Treprostinil Program Head
Organization: United Therapeutics Corporation
Phone: 919-485-8350
EMail: klaliberte@unither.com
Layout table for additonal information
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00775463     History of Changes
Other Study ID Numbers: TDE-DU-201
First Submitted: October 17, 2008
First Posted: October 20, 2008
Results First Submitted: January 31, 2014
Results First Posted: March 17, 2014
Last Update Posted: March 17, 2014