futility analysis showed low probability of detecting a significant difference

This study is designed to determine whether the use of oxandrolone, an anabolic steroid, can heal pressure ulcers in persons with spinal cord injury (SCI). In a Feasibility Study, three VA SCI Units will screen and randomize patients into treatment with oxandrolone or with placebo. Eleven other sites will screen patients to determine eligibility but will not treat patients with the agent. Following the Feasibility Study, all sites will participate in a blinded, randomized treatment study. A total of 400 patients will be enrolled over a four-year period. Any patient in a participating unit who has chronic SCI and a difficult-to-heal pelvic ulcer will be eligible for the study if other entry criteria are met. All enrolled patients will be followed for a period of 24 weeks to determine whether their target pressure ulcers heal. Those who are healed will be followed for an additional four weeks to determine whether the ulcer remains healed.

The primary objective is to determine whether SCI inpatients with a chronic Stage III or IV pressure ulcer of the pelvic region who are randomized to receive 24 weeks of optimized clinical care and an oral anabolic steroid agent (oxandrolone) will have a greater percent of healed pressure ulcers than those who receive placebo and the same optimized clinical care. The major secondary objective is to determine whether the healed pressure ulcer will remain healed for at least 8 weeks.

Subjects are registered into a 4 week screening phase to be followed with weekly photos of the ulcer and if healed less than 30% (from the day 1 photo to the day 28 photo) with standard clinical care, they are introduced to the treatment phase (randomized) and followed for another 24 weeks on either oxandrolone or placebo. Wounds that heal (remain closed for at least 96 hours) are then subject to 2 four week follow up visits.

Criteria for entering the screening phase are simple: either gender, age 18 years or older, inpatient with SCI or equivalent spinal cord damage and at least 1 Stage III or IV (indicating a severe wound, <260cm2) pressure ulcer of the pelvic region.

September 2006 - year one report submitted and approved by Central Office. Plan to add up to 3 more sites in the next year.

January 2007 - site #16 (San Antonio) is approved by Veterans Affairs Cooperative Studies Program Central Office to be invited.

Inclusion Criteria:

SCREENING PHASE:

1. Male or female inpatient with SCI or equivalent spinal cord damage.
2. At least one Stage III or IV (including a severe wound, <260cm2) pressure ulcer of the pelvic region.

TREATMENT PHASE:

1. documentation (through screening phase) of difficult to heal (defined as <30% area reduction) or worsening status of the pressure ulcer for at least 28 days as inpatient (screening phase)

Exclusion Criteria:

SCREENING PHASE:

1. Persons who are candidates for and elect to have reconstructive flap surgery of the TPU;
2. Persons with known osteomyelitis who have not been, or refuse to be, adequately treated with appropriate antibiotic treatment for at least 6 weeks and/or appropriate surgical procedures, as determined by the patients' physician, as well as patients who have not had resolution of osteomyelitis after 3 months of antibiotic and/or surgical care.
3. Psychopathology (documentation in the medical record or history of self-abusive behavior specific to pressure ulcer healing which may or may not include major or minor psychiatric illness) that may conflict with study objectives;
4. Previously diagnosed active malignant disease;
5. Suspicion of skin cancer at the pressure ulcer site (a biopsy-negative patient is not excluded, nor is a biopsy-positive patient excluded after a curative excision of the lesion);
6. Radiation therapy in the pressure ulcer field at anytime during the patient's lifetime;
7. Life expectancy less than 12 months;
8. Nephrosis, hemodialysis or chronic ambulatory peritoneal dialysis therapy;
9. AIDS patients at immunological risk of infectious complications defined as any of the following: (1) CD4 count <100 cells/ L or (2) CD4 count 100 to 200 cells/ L and WBC < 4,000 cells/ L or (3) a confirmed viral load within the past 6 months;
10. Administration of oxandrolone or another anabolic agent (not including testosterone replacement therapy) within the past 6 months;
11. A known hypersensitivity to anabolic steroid medications (specifically oxandrolone);
12. Coronary athersclerosis with unstable angina pectoris or a history within the past 3 months of an acute myocardial event or decompensated congestive heart failure.
13. Inability or unwillingness of the subject or surrogate to provide informed consent.

TREATMENT PHASE:

1. TPU >200 cm2 surface area of the pelvic region
2. Pressure ulcers with a clinical impression that are not expected to heal, such as those with: osteomyelitis (defined as persons with known osteomyelitis who have not been, or refuse to be, adequately treated with appropriate antibiotic treatment for at least 6 weeks and/or appropriate surgical procedures, as determined by the patients' physician, as well as patients who have not had resolution of osteomyelitis after 3 months of antibiotic and/or surgical care), sinus tracts suggestive of active osteomyelitis, communication to the synovial space, or other conditions;
3. Patient had flap surgery of the TPU during the Screening Phase;
4. Multiple full-thickness pressure ulcers that have a body surface area totaling >500cm2;
5. Clinical and/or laboratory evidence suggestive of prostate cancer;
6. Elevated liver function tests (AST >112 IU/L or bilirubin >3mg/dl);
7. Diabetes mellitus with less than optimal glycemic control (HbA1c >8.0%);
8. Received moderate (equivalent to prednisone 40 to 60 mg/d) or high dose (equivalent to prednisone >60 mg/d) systemic corticosteroids for at least 4 weeks, immunosuppressive agents, anti-cancer agents, or any radiation therapy within 30 days prior to randomization or are likely to receive one of these therapies during study participation;
9. Initiating or continuing therapy with appetite stimulants (e.g., Megase);
10. Current pharmacological therapy for hepatitis B or C infection;
11. Pregnancy or lactating female;
12. Females of child-bearing potential who are unwilling to agree to abstinence from sexual intercourse or the use of two reliable forms of contraception during the study; males unwilling to agree to abstinence from sexual intercourse or use of a condom during the study;
13. Expected use of oral anticoagulants (e.g. warfarin sodium) during the treatment phase;
14. Hypercalcemia;
15. Coronary athersclerosis with unstable angina pectoris or a history within the past 3 months of an acute myocardial event or decompensated congestive heart failure;
16. Participation in another active treatment clinical trial;
17. Inability or unwillingness of the subject or surrogate to provide informed consent.