Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers

Susan P. Perrine

Status and phase: Completed; Phase 2

Conditions: Skin Ulcers; Sickle Cell Anemia

Treatments: Drug: Arginine Butyrate; Other: Standard local care dressing

Study type: Interventional

Funder types: Other

Identifiers

NCT00004412

IND 36,957 (Other Identifier)

199/13302

BUSM-FDR001376 (Other Identifier)

Details and patient eligibility

About

OBJECTIVES: I. Compare the efficacy of local care alone vs local care plus arginine butyrate in terms of healing rate in patients with refractory sickle cell ulcers.

II. Determine the effect of arginine butyrate therapy on tissue factors related to promotion or inhibition of wound healing in these patients.

III. Determine whether the regimen used in this study is appropriate for testing in pivotal trials.

Full description

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive arginine butyrate IV over 6-9 hours at night 5 days a week for 12 weeks, plus concurrent standard local therapy consisting of cleaning, saline irrigation, and dressing changes as prescribed by each patient's physician. Patients who experience progressive healing receive arginine butyrate 3-4 times a week. Arginine butyrate treatment may be discontinued and reinstated following a single 2 week medical complication.

Arm II: Patients receive standard local therapy alone for 12 weeks. Patients randomized to arm II may cross over to receive arginine butyrate if no or less than 25% healing is observed after 12 weeks.

Patients whose ulcers have closed by at least 15% per cycle may receive 2 additional 8-week cycles of arginine butyrate therapy and are followed for 2 months after healing is completed.

Enrollment: 23 patients

Sex: All

Ages: 16 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

PROTOCOL CRITERIA

INCLUSION:

--Disease Characteristics-- Significant sickle cell syndrome including Hemoglobin SS (HbSS), Hemoglobin S-beta thalassemia, and hemoglobin variants. Lower extremity or ankle ulcer (or ulcers) present for at least 6 months without healing --Patient Characteristics-- Age: 16-60 yrs Performance status: Not specified Hematopoietic: Not specified Hepatic: No hepatic compromise Transaminases no greater than 250 IU Renal: No renal compromise Creatinine no greater than 1.2 mg/mL (adults) Creatinine no greater than 0.9 mg/mL (teenagers) Other: Not pregnant Fertile patients must use effective contraception No poorly controlled seizure disorders No other secondary conditions that might inhibit immune function

• Prior/Concurrent Therapy Other: Must be treated with antibiotics prior to entry for complicating cellulitis or secondary infections

EXCLUSION :

--Prior/Concurrent Therapy-- Biologic therapy: chronic transfusion therapy Chemotherapy: prior or concurrent cancer chemotherapy concurrent butyrate derivatives Endocrine therapy: concurrent corticosteroid therapy Radiotherapy: Not specified Surgery: Not specified --Patient Characteristics-- Hepatic: hepatic compromise Transaminases greater than 250 IU Renal: renal compromise Creatinine greater than 1.2 mg/mL (adults) Creatinine greater than 0.9 mg/mL (teenagers) Other: pregnant; Fertile patients with no effective contraception Poorly controlled seizure disorders other secondary conditions that might inhibit immune function

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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23 participants in 3 patient groups

Standard local care dressing

Other group

Description:

Each subject provided his/her own dressing e.g,standard local care includes cleaning, saline irrigation, dressing changes only for 8 weeks twice a week.

Treatment:

Other: Standard local care dressing

Arginine Butyrate

Experimental group

Description:

Arginine Butyrate IV plus Standard local care dressing for a total of 12 weeks. Low dose 500 mg/kg or, increased dose 750 mg/kg. First week AB given 5 days in a row, over 6 to 12hours.

Treatment:

Drug: Arginine Butyrate

Other: Standard local care dressing

Crossover

Other group

Description:

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.

Treatment:

Drug: Arginine Butyrate

Other: Standard local care dressing