Oxandrolone to Heal Pressure Ulcers

• Sponsor: US Department of Veterans Affairs (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT00101361
• Collaborator: (none)
• Enrollment: 212
• Locations: 16
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 13.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pressure Ulcer	Drug: Oxandrolone; Drug: Placebo	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: CSP #535 - Anabolic Steroid Therapy on Pressure Ulcer Healing in Persons With Spinal Cord Injury
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 oxandrolone	Drug: Oxandrolone; Patients will receive oxandrolone (10mg BID) until full healing occurs or for 24 weeks, which ever comes first.
Placebo Comparator: 2 placebo	Drug: Placebo; Patients will receive an identically appearing placebo capsule until full healing occurs or for 24 weeks, which ever comes first.

Outcome Measures

Primary Outcome Measures

1. A Healed Pressure Ulcer [healing was measured from randomization to full healing or 24 weeks, whichever occured first.]

   Patients remained in treatment until full healing of the target pressure ulcer (defined as re-epithelialization to a cicatrix with a dry surface and zero open area for a minimum of 96 hours) or 24 weeks, whichever occured first.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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;

1. Clinical and/or laboratory evidence suggestive of prostate cancer;

2. Elevated liver function tests (AST >112 IU/L or bilirubin >3mg/dl);

3. Diabetes mellitus with less than optimal glycemic control (HbA1c >8.0%);

4. 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;

5. Initiating or continuing therapy with appetite stimulants (e.g., Megase);

6. Current pharmacological therapy for hepatitis B or C infection;

7. Pregnancy or lactating female;

8. 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;

9. Expected use of oral anticoagulants (e.g. warfarin sodium) during the treatment phase;

10. Hypercalcemia;

11. Coronary athersclerosis with unstable angina pectoris or a history within the past 3 months of an acute myocardial event or decompensated congestive heart failure;

12. Participation in another active treatment clinical trial;

13. Inability or unwillingness of the subject or surrogate to provide informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Medical Center, Long Beach	Long Beach	California	United States	90822
2	VA Palo Alto Health Care System	Palo Alto	California	United States	94304-1290
3	VA San Diego Healthcare System, San Diego	San Diego	California	United States	92161
4	VA Medical Center, Miami	Miami	Florida	United States	33125
5	James A. Haley Veterans Hospital, Tampa	Tampa	Florida	United States	33612
6	VA Medical Center, Augusta	Augusta	Georgia	United States	30904
7	Edward Hines, Jr. VA Hospital	Hines	Illinois	United States	60141-5000
8	VA Boston Healthcare System, Brockton Campus	Brockton	Massachusetts	United States	02301
9	VA Medical Center, St Louis	St Louis	Missouri	United States	63106
10	VA Medical Center, Bronx	Bronx	New York	United States	10468
11	VA Medical Center, Cleveland	Cleveland	Ohio	United States	44106
12	VA North Texas Health Care System, Dallas	Dallas	Texas	United States	75216
13	Michael E. DeBakey VA Medical Center (152)	Houston	Texas	United States	77030
14	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia	United States	23249
15	Zablocki VA Medical Center, Milwaukee	Milwaukee	Wisconsin	United States	53295-1000
16	VA Medical Center, San Juan	San Juan		Puerto Rico	00921

Sponsors and Collaborators

• US Department of Veterans Affairs

Investigators

• Study Chair: William Bauman, MD, VA Medical Center, Bronx

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT00101361
• Other Study ID Numbers: 535
• First Posted: Jan 10, 2005
• Last Update Posted: Dec 20, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by US Department of Veterans Affairs: dermatologic; skin; clinical trial; androgen/anabolic
• Additional relevant MeSH terms: Pressure Ulcer; Ulcer; Oxandrolone

Study Results

Participant Flow

Recruitment Details	enrollment started 08/01/2005 and ended 10/10/2008 at 15 VA Medical Centers. Subjects were randomized only after a four week screening phase.
Pre-assignment Detail	Potential participants were screened for four weeks to determine eligibility based on documentation of a difficult-to-heal or worsening status of the pressure ulcer as an inpatient.

Arm/Group Title	1 Oxandrolone	2 Placebo
Arm/Group Description	oxandrolone - two 5mg capsules twice daily	placebo - two capsules twice daily
Period Title: Overall Study
STARTED	108	104
COMPLETED	108	104
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Oxandrolone	Placebo	Total
Arm/Group Description	Oxandrolone	placebo	Total of all reporting groups
Overall Participants	108	104	212
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	82 75.9%	83 79.8%	165 77.8%
>=65 years	26 24.1%	21 20.2%	47 22.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.4 (10.4)	57.3 (11.6)	57.9 (11.1)
Sex: Female, Male (Count of Participants)
Female	2 1.9%	0 0%	2 0.9%
Male	106 98.1%	104 100%	210 99.1%
Region of Enrollment (participants) [Number]
United States	107 99.1%	103 99%	210 99.1%
Puerto Rico	1 0.9%	1 1%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	A Healed Pressure Ulcer
Description	Patients remained in treatment until full healing of the target pressure ulcer (defined as re-epithelialization to a cicatrix with a dry surface and zero open area for a minimum of 96 hours) or 24 weeks, whichever occured first.
Time Frame	healing was measured from randomization to full healing or 24 weeks, whichever occured first.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 Oxandrolone	2 Placebo
Arm/Group Description	oxandrolone - two 5mg capsules twice daily	placebo - two capsules twice daily
Measure Participants	108	104
Number [participants]	26 24.1%	31 29.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1 Oxandrolone, 2 Placebo
	Comments	For spinal cord injury patients with a Stage III or IV pressure ulcer of the pelvic region who receive 24 weeks or less of optimized clinical care (i.e., guideline-driven care with nutritional support) compared with optimized clinical care and an oral anabolic steroid agent (oxandrolone) there will be no difference in the percent of healed pressure ulcers.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	the required sample size of 400 participants provided 85% power to detect an increase in healing from 25% in the placebo group to 40% in the oxandrolone group, as assuming a 0.05 (2-sided) type I error, 13% rate of loss to follow up, and a test of proportions by using an arcsine transformation.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.7
	Confidence Interval	(2-Sided) 95%; -17.5 to 6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	years, 5 months
Adverse Event Reporting Description	Adverse events were reported for each event not each subject, therefore participants could have one or more events. The total events as reported is expected to surpass the total participants. The total participants with at least one adverse event (AE) is 95 oxandrolone and 85 placebo.
Arm/Group Title	1 Oxandrolone		2 Placebo
Arm/Group Description	oxandrolone - two 5mg capsules twice daily		placebo - two capsules twice daily
All Cause Mortality
	1 Oxandrolone		2 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1 Oxandrolone		2 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/108 (8.3%)		16/104 (15.4%)
Gastrointestinal disorders
small bowel obstruction, renal failure	0/108 (0%)	0	1/104 (1%)	1
Infections and infestations
death	0/108 (0%)	0	1/104 (1%)	1
Metabolism and nutrition disorders
death	0/108 (0%)	0	1/104 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
oral cancer	0/108 (0%)	0	1/104 (1%)	1
Respiratory, thoracic and mediastinal disorders
death	3/104 (2.9%)	3	3/104 (2.9%)	3
Surgical and medical procedures
elective bladder stone removal	1/108 (0.9%)	1	0/104 (0%)	0
myocutaneous flap surgery	5/108 (4.6%)	5	9/104 (8.7%)	9
Other (Not Including Serious) Adverse Events
	1 Oxandrolone		2 Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	95/108 (88%)		85/104 (81.7%)
Blood and lymphatic system disorders
anemia	17/108 (15.7%)	17	4/104 (3.8%)	4
Gastrointestinal disorders
constipation or diarrhea	8/108 (7.4%)	8	10/104 (9.6%)	10
nausea / vomitting	10/108 (9.3%)	10	10/104 (9.6%)	10
Infections and infestations
infection	13/108 (12%)	13	9/104 (8.7%)	9
osteomylitis	5/108 (4.6%)	5	6/104 (5.8%)	6
pneumonia	14/108 (13%)	14	6/104 (5.8%)	6
urinary tract infection	37/108 (34.3%)	37	28/104 (26.9%)	28
Injury, poisoning and procedural complications
fever	17/108 (15.7%)	17	10/104 (9.6%)	10
Investigations
elevated liver enzyme levels	35/108 (32.4%)	35	3/104 (2.9%)	3
Skin and subcutaneous tissue disorders
non-Target Pressure Ulcer (TPU) skin ulcer	13/108 (12%)	13	8/104 (7.7%)	8
skin rash / complication	15/108 (13.9%)	15	10/104 (9.6%)	10

Limitations/Caveats

Selection of severe wounds may have reduced treatment response. The study was terminated after a futility analysis showed a low probability of detecting a significant difference between groups.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.