Trial Outcomes & Findings for Evaluation of Cilostazol in Combination With L-Carnitine (NCT NCT00822172)
NCT ID: NCT00822172
Last Updated: 2019-11-29
Results Overview
Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
COMPLETED
PHASE4
164 participants
Baseline, Day 180
2019-11-29
Participant Flow
The first participant was randomized on September 19th, 2008 and the last subject was randomized on May 7, 2010. Clinical study sites were a mixture of university/hospital settings, Veteran Affairs hospitals, professional research centers and medical clinics.
The study included a cilostazol run in period. From the 164 participants who remained eligible at the end of the run in period, only 1 participant did not subsequently receive treatment. This was due to voluntary withdrawal by the participant.
Participant milestones
| Measure |
Cilostazol + L-Carnitine
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Overall Study
STARTED
|
80
|
83
|
|
Overall Study
COMPLETED
|
65
|
64
|
|
Overall Study
NOT COMPLETED
|
15
|
19
|
Reasons for withdrawal
| Measure |
Cilostazol + L-Carnitine
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Overall Study
Adverse Event
|
10
|
12
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
4
|
|
Overall Study
site closed
|
0
|
1
|
|
Overall Study
Other
|
0
|
1
|
Baseline Characteristics
Evaluation of Cilostazol in Combination With L-Carnitine
Baseline characteristics by cohort
| Measure |
Cilostazol + L-Carnitine
n=80 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=83 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Total
n=163 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
43 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
70 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
37 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
|
Age, Continuous
|
65.8 years
STANDARD_DEVIATION 9.39 • n=5 Participants
|
67.3 years
STANDARD_DEVIATION 8.00 • n=7 Participants
|
66.5 years
STANDARD_DEVIATION 8.74 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
66 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
133 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
80 participants
n=5 Participants
|
83 participants
n=7 Participants
|
163 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 180Population: modified Intent to Treat Population (mITT)
Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
Outcome measures
| Measure |
Cilostazol + L-Carnitine
n=74 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=71 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Change From Baseline in Peak Walking Time (PWT) at Day 180
|
0.241 Log Minutes
Standard Deviation 0.3836
|
0.134 Log Minutes
Standard Deviation 0.3343
|
SECONDARY outcome
Timeframe: Baseline, Day 180Population: Per Protocol (PP) Population
Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
Outcome measures
| Measure |
Cilostazol + L-Carnitine
n=60 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=58 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Change From Baseline in Peak Walking Time at Day 180
|
0.267 Log Minutes
Standard Deviation 0.3516
|
0.145 Log Minutes
Standard Deviation 0.3124
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: modified Intent to Treat Population (mITT)
Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
Outcome measures
| Measure |
Cilostazol + L-Carnitine
n=69 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=65 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Change From Baseline in Peak Walking Time at Day 90
|
0.166 Log Minutes
Standard Deviation 0.3571
|
0.139 Log Minutes
Standard Deviation 0.3293
|
SECONDARY outcome
Timeframe: Baseline, Day 180Population: modified Intent to Treat Population (mITT)
Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. The time during the conduct of the exercise treadmill test at which the subject first reported claudication symptoms is referred to as the claudication onset time (COT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
Outcome measures
| Measure |
Cilostazol + L-Carnitine
n=66 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=66 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Change From Baseline in Claudication Onset Time at Day 180
|
1.065 Log Minutes
Standard Deviation 0.6680
|
0.896 Log Minutes
Standard Deviation 0.7364
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: modified Intent to Treat Population (mITT)
Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. The time during the conduct of the exercise treadmill test at which the subject first reported claudication symptoms is referred to as the claudication onset time (COT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
Outcome measures
| Measure |
Cilostazol + L-Carnitine
n=68 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=63 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Change From Baseline in Claudication Onset Time at Day 90
|
1.001 Log Minutes
Standard Deviation 0.6476
|
0.815 Log Minutes
Standard Deviation 0.7000
|
SECONDARY outcome
Timeframe: Baseline, Day 180Population: modified Intent to Treat Population (mITT)
Subjects completed the Walking Impairment Questionnaire (WIQ) whereby they were asked about their maximal walking distance before having to rest as a result of claudication symptoms associated with their peripheral artery disease (PAD). The WIQ was administered at the Baseline, Day 90, and Day 180 visits. On the WIQ subjects were asked a series of questions related to their degree of physical difficulty that best described how hard it was for the subject to walk on level ground without stopping to rest. The questions began by asking the degree of difficulty walking around indoors, then 50 feet, 150 feet, 300 feet, 600 feet, 900 feet, and lastly 1500 feet. The responses range from None (best outcome) to Slight, then Some, then Much, then lastly Unable (worst outcome). The walking distance score was calculated from the 7 questions in the section by way of a weighted sum. A score of 100 indicated no walking impairment. A score of 0 corresponded to the highest degree of walking impairment
Outcome measures
| Measure |
Cilostazol + L-Carnitine
n=68 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=68 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Change From Baseline in Walking Impairment Questionnaire for Walking Distance at Day 180
|
13.20 score on a scale
Standard Deviation 22.001
|
6.57 score on a scale
Standard Deviation 24.288
|
SECONDARY outcome
Timeframe: Baseline, Day 90Population: modified Intent to Treat Population (mITT)
Subjects completed the Walking Impairment Questionnaire (WIQ) whereby they were asked about their maximal walking distance before having to rest as a result of claudication symptoms associated with their peripheral artery disease (PAD). The WIQ was administered at the Baseline, Day 90, and Day 180 visits. On the WIQ subjects were asked a series of questions related to their degree of physical difficulty that best described how hard it was for the subject to walk on level ground without stopping to rest. The questions began by asking the degree of difficulty walking around indoors, then 50 feet, 150 feet, 300 feet, 600 feet, 900 feet, and lastly 1500 feet. The responses range from None (best outcome) to Slight, then Some, then Much, then lastly Unable (worst outcome). The walking distance score was calculated from the 7 questions in the section by way of a weighted sum. A score of 100 indicated no walking impairment. A score of 0 corresponded to the highest degree of walking impairment
Outcome measures
| Measure |
Cilostazol + L-Carnitine
n=71 Participants
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=66 Participants
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Change From Baseline in Walking Impairment Questionnaire for Walking Distance at Day 90
|
12.98 score on a scale
Standard Deviation 25.251
|
10.01 score on a scale
Standard Deviation 21.354
|
Adverse Events
Cilostazol + L-Carnitine
Cilostazol + Placebo
Serious adverse events
| Measure |
Cilostazol + L-Carnitine
n=80 participants at risk
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=83 participants at risk
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
1.2%
1/80 • Number of events 1
|
1.2%
1/83 • Number of events 1
|
|
Renal and urinary disorders
Prostate cancer
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Renal and urinary disorders
Urosepsis
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Vascular disorders
Arterial thrombosis limb
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Vascular disorders
Cerebrovascular accident
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/80
|
1.2%
1/83 • Number of events 1
|
|
General disorders
Abdominal hernia
|
2.5%
2/80 • Number of events 2
|
0.00%
0/83
|
|
Renal and urinary disorders
Ureteric fistula
|
1.2%
1/80 • Number of events 1
|
0.00%
0/83
|
|
Musculoskeletal and connective tissue disorders
Cervicobrachial syndrome
|
1.2%
1/80 • Number of events 1
|
0.00%
0/83
|
|
Musculoskeletal and connective tissue disorders
Cellulitis
|
1.2%
1/80 • Number of events 1
|
0.00%
0/83
|
|
Endocrine disorders
Pancreatitis acute
|
1.2%
1/80 • Number of events 1
|
0.00%
0/83
|
|
Cardiac disorders
Myocardial infarction
|
2.5%
2/80 • Number of events 3
|
0.00%
0/83
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.2%
1/80 • Number of events 1
|
0.00%
0/83
|
|
Cardiac disorders
Sick sinus syndrome
|
1.2%
1/80 • Number of events 1
|
0.00%
0/83
|
Other adverse events
| Measure |
Cilostazol + L-Carnitine
n=80 participants at risk
Levocarnitine tartrate : Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
Cilostazol + Placebo
n=83 participants at risk
cilostazol : Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.
Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
11.2%
9/80 • Number of events 16
|
9.6%
8/83 • Number of events 17
|
|
Nervous system disorders
Headache
|
12.5%
10/80 • Number of events 15
|
16.9%
14/83 • Number of events 17
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place