Trial Outcomes & Findings for Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Diffuse Systemic Sclerosis (NCT NCT01093885)
NCT ID: NCT01093885
Last Updated: 2018-11-29
Results Overview
Using validated clinical response measurements such as the modified Rodnan skin score (MRSS) we will determine whether combination therapy will effect morbidity in systemic sclerosis. The modified Rodnan skin score has a range from 0-51 with higher numbers being worse skin involvement.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
15 participants
Primary outcome timeframe
Baseline and 12 months
Results posted on
2018-11-29
Participant Flow
Recruitment took place in the clinic over a 5 year period
None of the patients were able to increase the dosage of ambrisentan from the initial dose of 5 mg to 10 mg.
Participant milestones
| Measure |
Open Label: Medication Ambrisentan
Open label study of Ambrisentan.
Ambrisentan will begin at 5mg daily for the first month.
Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.
Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
10
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Open Label: Medication Ambrisentan
Open label study of Ambrisentan.
Ambrisentan will begin at 5mg daily for the first month.
Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.
Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Study of Ambrisentan With Antifibrotic Agent Combination Therapy in Diffuse Systemic Sclerosis
Baseline characteristics by cohort
| Measure |
Open Label: Medication Ambrisentan
n=15 Participants
Open label study of Ambrisentan.
Ambrisentan will begin at 5mg daily for the first month.
Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.
Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
|
|---|---|
|
Age, Continuous
|
47.6 years
STANDARD_DEVIATION 10.7 • n=99 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
15 Participants
n=99 Participants
|
|
Extent of skin sclerosis
|
21 units on a scale
STANDARD_DEVIATION 7.4 • n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline and 12 monthsUsing validated clinical response measurements such as the modified Rodnan skin score (MRSS) we will determine whether combination therapy will effect morbidity in systemic sclerosis. The modified Rodnan skin score has a range from 0-51 with higher numbers being worse skin involvement.
Outcome measures
| Measure |
Open Label: Medication Ambrisentan
n=15 Participants
Open label study of Ambrisentan.
Ambrisentan will begin at 5mg daily for the first month.
Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.
Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
|
|---|---|
|
The Benefit That an Antifibrotic Agent and Ambrisentan Combination Have on the Cutaneous Involvement of Patients With Early Diffuse Systemic Sclerosis by Utilizing the MRSS
mRss mean for group at study entry
|
21 units on a scale
Standard Deviation 7.4
|
|
The Benefit That an Antifibrotic Agent and Ambrisentan Combination Have on the Cutaneous Involvement of Patients With Early Diffuse Systemic Sclerosis by Utilizing the MRSS
mRss mean for group at end of Study- to 12 months
|
13 units on a scale
Standard Deviation 11.2
|
SECONDARY outcome
Timeframe: Baseline vs Month 12.Population: 15 subjects enrolled, 5 subjects withdrew. Data analyzed was only for the 10 subjects who completed the 12 month visit and had both a baseline and a 12 month SF-36 form completed
The SF-36 form is a patient reported survey of patient health. The comparison status was analyzed between baseline and 12 months. The SF-36 has a range of 0-100 with higher numbers suggestive of better patient health
Outcome measures
| Measure |
Open Label: Medication Ambrisentan
n=10 Participants
Open label study of Ambrisentan.
Ambrisentan will begin at 5mg daily for the first month.
Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.
Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
|
|---|---|
|
Systemic Sclerosis Quality of Life Assessed by the SF-36.
SF-36 mean for group at study entry
|
62 units on a scale
Standard Deviation 23.3
|
|
Systemic Sclerosis Quality of Life Assessed by the SF-36.
SF-36 mean of group at study end -12 months
|
65.9 units on a scale
Standard Deviation 25.7
|
Adverse Events
Open Label: Medication Ambrisentan
Serious events: 4 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open Label: Medication Ambrisentan
n=15 participants at risk
Open label study of Ambrisentan.
Ambrisentan will begin at 5mg daily for the first month.
Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.
Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Product Issues
Lower Extremity Swelling
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Gastrointestinal disorders
Adynamic ileus
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
Other adverse events
| Measure |
Open Label: Medication Ambrisentan
n=15 participants at risk
Open label study of Ambrisentan.
Ambrisentan will begin at 5mg daily for the first month.
Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week. Subjects will continue their present dose and schedule of disease modifying/antifibrotic medication for the duration of the study.
Ambrisentan: Drug is dispensed in tablet form. Ambrisentan with anti-fibrotic to assess benefit on skin
Dosing of ambrisentan will begin at 5mg daily for the first month. Half the patients will remain at 5mg daily, while the remaining patients will be increased to a maintenance dose of 10mg daily on the fourth week.
|
|---|---|
|
Cardiac disorders
Hypertension
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Immune system disorders
Flu
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Infections and infestations
Sore throat
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Gastrointestinal disorders
Gastrointestinal illness
|
20.0%
3/15 • Number of events 3 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.3%
2/15 • Number of events 2 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Infections and infestations
Urinary Tract Infection
|
6.7%
1/15 • Number of events 3 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Infections and infestations
Nasal congestion
|
20.0%
3/15 • Number of events 3 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
General disorders
Hot flashes
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
General disorders
Facial Flushing
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Cardiac disorders
Ankle Swelling
|
26.7%
4/15 • Number of events 4 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Cardiac disorders
Hypotension
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Shoulder Pain
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Eye disorders
Cataract Removal
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Bilateral Flank Pain
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Bilateral Finger Swelling
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Bilateral Wrist Swelling
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Skin and subcutaneous tissue disorders
Basal Cell Skin cancer
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
General disorders
Dizziness
|
13.3%
2/15 • Number of events 2 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Leg Cramps
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Left Upper Quadrant Pain
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Joint Pain
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
General disorders
Fatigue
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
General disorders
Mouth Ulcers
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Gastrointestinal disorders
Increased Reflux
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Right Shoulder Weakness
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
|
Musculoskeletal and connective tissue disorders
Right Hip Weakness
|
6.7%
1/15 • Number of events 1 • 1 year
Serious Adverse Events Other Adverse Events
|
Additional Information
Dr. Chris Derk
University of Pennsylvania Health System
Phone: 215-662-2792
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place