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

This study has been completed.
Sponsor:
Collaborators:
Boston Medical Center
University of Illinois at Chicago
Icahn School of Medicine at Mount Sinai
University of Tennessee Health Science Center
Schneider Children's Medical Center, Israel
Information provided by (Responsible Party):
Susan P. Perrine, Boston University
ClinicalTrials.gov Identifier:
NCT00004412
First received: October 18, 1999
Last updated: March 18, 2015
Last verified: March 2015

October 18, 1999
March 18, 2015
September 1997
December 2002   (final data collection date for primary outcome measure)
Healing Defined as a Decrease in Ulcer Area by at Least 25% of the Initial Area [ Time Frame: participants were followed for an average of 3 months ] [ Designated as safety issue: No ]

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.

Not Provided
Complete list of historical versions of study NCT00004412 on ClinicalTrials.gov Archive Site
% Ulcers Which Completely Healed in Each Group, After 3 Months [ Time Frame: two additional courses of 8 week cycles ] [ Designated as safety issue: No ]
Control Arm: given option to crossover to Treatment Arm if, ulcers have not closed after 12 weeks standard local care alone.
Not Provided
Not Provided
Not Provided
 
Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers
Phase II Trial of Arginine Butyrate for Treatment of Refractory Leg Ulcers in Sickle Cell Disease or Beta Thalassemia

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Skin Ulcers
  • Sickle Cell Anemia
  • Drug: Arginine Butyrate
    To determine if Arginine Butyrate accelerates healing of refractory leg ulcers over Standard Local Care alone.
  • Other: Standard local care dressing
    To heal leg ulcers.
  • Standard local care dressing
    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.
    Intervention: Other: Standard local care dressing
  • Experimental: Arginine Butyrate
    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.
    Interventions:
    • Drug: Arginine Butyrate
    • Other: Standard local care dressing
  • 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 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.
    Interventions:
    • Drug: Arginine Butyrate
    • Other: Standard local care dressing
McMahon L, Tamary H, Askin M, Adams-Graves P, Eberhardt RT, Sutton M, Wright EC, Castaneda SA, Faller DV, Perrine SP. A randomized phase II trial of Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers. Br J Haematol. 2010 Dec;151(5):516-24. doi: 10.1111/j.1365-2141.2010.08395.x. Epub 2010 Oct 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
23
February 2005
December 2002   (final data collection date for primary outcome measure)

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

Both
16 Years to 60 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00004412
199/13302, BUSM-FDR001376, IND 36,957
No
Not Provided
Not Provided
Susan P. Perrine, Boston University
Susan P. Perrine
  • Boston Medical Center
  • University of Illinois at Chicago
  • Icahn School of Medicine at Mount Sinai
  • University of Tennessee Health Science Center
  • Schneider Children's Medical Center, Israel
Study Chair: Douglas V. Faller Boston University
Boston University
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP