Trial Outcomes & Findings for Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers (NCT NCT00004412)
NCT ID: NCT00004412
Last Updated: 2015-03-31
Results Overview
Treatment Arm: The AB is given as an IV infusion at 500 mg/kg over 6-9 hrs. 5 days per week for 12 weeks. After 12 weeks of therapy, if he ulcer has decreased by 25% , the AB may be continued for additional 8 weeks (twice) or, until ulcer closes plus 2 weeks, additionally. Ulcers photographed, traced, and ulcer areas calculated by computerized planimetry.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
23 participants
Primary outcome timeframe
participants were followed for an average of 3 months
Results posted on
2015-03-31
Participant Flow
Study began 1998, contacted physicians at several medical centers with patients under their care for SCD with refractory leg ulcers. Electronic materials describing the study and its sponsor were transmitted to medical centers.
Participant milestones
| Measure |
Standard Local Care Dressing
Standard local care includng cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.
|
Arginine Butyrate
Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours.
|
Crossover
Patients are randomly assigned (following a table of random numbers prepared by a blinded statistician) between two arms of the study. Arm I is Allevyn Hydrophilic PU dressing (standard local care) only, and Arm II is standard local care plus Arginine Butyrate (AB), the Investigational New Drug. Ulcers observed \& traced weekly. Ulcer area calculated by computerized planimetry. After 12 weeks of therapy, if the ulcer size decreased by at least 25%, the AB may be continued for another 8 weeks (twice), or until the ulcer closes, plus an additional 2 weeks. The patients randomized to the Control Arm ( standard local care) were given the option of crossing over to Arm II If, ulcers did not close after 8 weeks of standard local care.
|
|---|---|---|---|
|
Randomized Period
STARTED
|
11
|
12
|
0
|
|
Randomized Period
COMPLETED
|
8
|
12
|
0
|
|
Randomized Period
NOT COMPLETED
|
3
|
0
|
0
|
|
Crossover Period
STARTED
|
8
|
12
|
3
|
|
Crossover Period
COMPLETED
|
8
|
12
|
3
|
|
Crossover Period
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Standard Local Care Dressing
Standard local care includng cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.
|
Arginine Butyrate
Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours.
|
Crossover
Patients are randomly assigned (following a table of random numbers prepared by a blinded statistician) between two arms of the study. Arm I is Allevyn Hydrophilic PU dressing (standard local care) only, and Arm II is standard local care plus Arginine Butyrate (AB), the Investigational New Drug. Ulcers observed \& traced weekly. Ulcer area calculated by computerized planimetry. After 12 weeks of therapy, if the ulcer size decreased by at least 25%, the AB may be continued for another 8 weeks (twice), or until the ulcer closes, plus an additional 2 weeks. The patients randomized to the Control Arm ( standard local care) were given the option of crossing over to Arm II If, ulcers did not close after 8 weeks of standard local care.
|
|---|---|---|---|
|
Randomized Period
Moved to Crossover Period
|
3
|
0
|
0
|
Baseline Characteristics
Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers
Baseline characteristics by cohort
| Measure |
Standard Local Care Dressing
n=8 Participants
Standard local care dressing including cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.
|
Arginine Butyrate
n=12 Participants
Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours.
|
Crossover
n=3 Participants
Patients are randomly assigned (following a table of random numbers prepared by a blinded statistician) between two arms of the study. Arm I is Standard local care dressing only, and Arm II is standard local care plus Arginine Butyrate (AB), the Investigational New Drug. Ulcers observed \& traced weekly. Ulcer area calculated by computerized planimetry. After 12 weeks of therapy, if the ulcer size decreased by at least 25%, the AB may be continued for another 8 weeks (twice), or until the ulcer closes, plus an additional 2 weeks. The patients randomized to the Control Arm ( standard local care) were given the option of crossing over to Arm II If, ulcers did not close after 8 weeks of standard local care.
|
Total
n=23 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
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
31 years
STANDARD_DEVIATION 12.57478 • n=5 Participants
|
33 years
STANDARD_DEVIATION 9.14985 • n=7 Participants
|
31 years
STANDARD_DEVIATION 2.3094 • n=5 Participants
|
32 years
STANDARD_DEVIATION 1.1547 • n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
12 participants
n=7 Participants
|
2 participants
n=5 Participants
|
22 participants
n=4 Participants
|
|
Region of Enrollment
Israel
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: participants were followed for an average of 3 monthsPopulation: Per protocol
Treatment Arm: The AB is given as an IV infusion at 500 mg/kg over 6-9 hrs. 5 days per week for 12 weeks. After 12 weeks of therapy, if he ulcer has decreased by 25% , the AB may be continued for additional 8 weeks (twice) or, until ulcer closes plus 2 weeks, additionally. Ulcers photographed, traced, and ulcer areas calculated by computerized planimetry.
Outcome measures
| Measure |
Standard Local Care Dressing
n=25 number of ulcers
Standard local care includng cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.
|
Arginine Butyrate
n=37 number of ulcers
Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours.
|
|---|---|---|
|
Healing Defined as a Decrease in Ulcer Area by at Least 25% of the Initial Area
|
24 percentage of healed ulcers
|
78 percentage of healed ulcers
|
SECONDARY outcome
Timeframe: two additional courses of 8 week cyclesPopulation: Per Protocol
Control Arm: given option to crossover to Treatment Arm if, ulcers have not closed after 12 weeks standard local care alone.
Outcome measures
| Measure |
Standard Local Care Dressing
n=25 Number of ulcers
Standard local care includng cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.
|
Arginine Butyrate
n=48 Number of ulcers
Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours.
|
|---|---|---|
|
% Ulcers Which Completely Healed in Each Group, After 3 Months
|
8 percentage of completely healed ulcers
|
31 percentage of completely healed ulcers
|
Adverse Events
Standard Local Care Dressing
Serious events: 5 serious events
Other events: 1 other events
Deaths: 0 deaths
Arginine Butyrate
Serious events: 9 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard Local Care Dressing
n=11 participants at risk
Standard local care including cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.
|
Arginine Butyrate
n=15 participants at risk
Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours.
|
|---|---|---|
|
Blood and lymphatic system disorders
Vaso-occlusive crisis (VOC))
|
36.4%
4/11 • Number of events 13
|
46.7%
7/15 • Number of events 9
|
|
Vascular disorders
Thrombosis
|
0.00%
0/11
|
13.3%
2/15 • Number of events 2
|
|
Infections and infestations
Septic arthritis
|
0.00%
0/11
|
6.7%
1/15 • Number of events 1
|
|
Vascular disorders
Clotted Portacath
|
0.00%
0/11
|
6.7%
1/15 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Chronic Limb Pain
|
0.00%
0/11
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Head & Eye Pain
|
9.1%
1/11 • Number of events 1
|
0.00%
0/15
|
|
Vascular disorders
Hypotension
|
9.1%
1/11 • Number of events 1
|
0.00%
0/15
|
|
Gastrointestinal disorders
Bloody Diarrhea
|
9.1%
1/11 • Number of events 1
|
0.00%
0/15
|
|
Infections and infestations
Ulcer Infection
|
0.00%
0/11
|
6.7%
1/15 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Possible Celluitis
|
0.00%
0/11
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Pre-existing Osteomyelitis of Left Foot
|
0.00%
0/11
|
6.7%
1/15 • Number of events 1
|
|
Cardiac disorders
Pleural effusion and Pericardial Effusion
|
0.00%
0/11
|
6.7%
1/15 • Number of events 1
|
|
Cardiac disorders
Chest Pain , SOB
|
9.1%
1/11 • Number of events 1
|
0.00%
0/15
|
Other adverse events
| Measure |
Standard Local Care Dressing
n=11 participants at risk
Standard local care including cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.
|
Arginine Butyrate
n=15 participants at risk
Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 250 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 8 to 12hours.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
9.1%
1/11 • Number of events 1
|
0.00%
0/15
|
|
General disorders
Headache
|
9.1%
1/11 • Number of events 1
|
0.00%
0/15
|
|
Gastrointestinal disorders
Decreased Appetite
|
9.1%
1/11 • Number of events 1
|
0.00%
0/15
|
Additional Information
Douglas V. Faller, Ph.D., M.D., Susan P. Perrine, M.D.
Boston University School of Medicine
Phone: (617) 638-5639
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place