Venous Leg Ulcer
Conditions
Keywords
Venous leg ulcer, randomized trial, clinical trial, Dermagraft, compression therapy, surgical debridement, venous stasis, chronic ulcer, chronic wound, fibroblasts
Brief summary
This study randomly assigns patients with venous leg ulcers to receive standard therapy (compression) alone or compression plus Dermagraft(R). Dermagraft is a device containing live human fibroblasts grown on an absorbable Vicryl mesh. Patients are seen weekly until they heal or the 16-week treatment period is complete. Follow-up visits are conducted monthly for three months in order to assess patients for longer term safety.
Interventions
DEVICEDermagraft(R)
Weekly application of Dermagraft(R) with Profore compression as a secondary layer, in combination with systematic surgical wound debridement.
DEVICEProfore
Weekly application of Profore compression dressings, in combination with systematic surgical wound debridement.
Sponsors
Organogenesis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>18 years of age * ABI \> 0.80 * Three or fewer venous leg ulcers, if multiple must be separated by 2 cm * Ultrasound demonstrates venous reflux \>0.5 seconds * Study wound present for 1-24 months * Study wound 2-15 sq cm surface area * Clean, granulating wound * Patient able and willing to sign informed consent and comply with study procedures. * Women of childbearing potential must use birth control pills, barriers or abstinence and have a negative pregnancy test.
Exclusion criteria
* Wound etiology uncertain or not from venous hypertension. * BMI\>40 * Acute or chronic infectious skin disease * Allergy or intolerance to Profore(R) * Wound infection, cellulitis, osteomyelitis * \>2 weeks' treatment with immunosuppressive agents in recent past * Investigational drug use within 30 days * Severe malnutrition, drug and/or alcohol abuse * Malignant disease unless in remission for 5 years * History of radiation at the study site * Other conditions that could impede wound healing * Known history of HIV or AIDS * Prior participation in any Dermagraft study * Treatment with other bioengineered tissue products within 30 days * Unable to understand the aims and objectives of the trial * Inability to comply with study protocol * NYHA Class III or IV CHF * Uncontrolled diabetes mellitus * Dorsal foot ulcer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Healing of the Study Ulcer by Week 16. | 16 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-Complete Healing | From Week 0 visit to date subject's completely healed ulcer is 1st recorded as healed. If subject's ulcer not healed at 16 weeks, the time until CH was censored at 112 days. | Kaplan-Meier survival analysis of the time to achieve median (50%) Complete Healing response in each treatment group. |
Other
| Measure | Time frame |
|---|---|
| Complete Healing by Week 16: Ulcers <= 12 Months Duration | 16 weeks |
Countries
Austria, Estonia, Germany, Poland, South Africa, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Screening commenced in May 2009 and ended in November 2010. Study sites included vascular surgery, dermatology, and podiatry clinics. A total of 913 potential subjects were screened across 58 study centers; 395 subjects were screen failures. A total of 537 subjects were enrolled across 49 study centers.
Pre-assignment details
Prior to study enrollment, all subjects signing informed consent proceeded through a two-week run-in phase in which all subjects received standard-of-care study ulcer treatment. During this phase, any subject not meeting inclusion/exclusion criteria was considered a screen failure and removed from the study.
Participants by arm
| Arm | Count |
|---|---|
| Investigational Treatment (Dermagraft Plus Standard-of-Care) Weekly applications of Dermagraft and compression dressings, in combination with systematic surgical wound debridement. | 274 |
| Control (Standard-of-Care) Weekly application of compression dressings only, in combination with systematic surgical wound debridement. | 263 |
| Total | 537 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 7 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Other | 1 | 5 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 8 |
Baseline characteristics
| Characteristic | Investigational Treatment (Dermagraft Plus Standard-of-Care) | Control (Standard-of-Care) | Total |
|---|---|---|---|
| Age, Continuous | 63.1 Years STANDARD_DEVIATION 13.04 | 63.2 Years STANDARD_DEVIATION 14.46 | 63.1 Years STANDARD_DEVIATION 13.74 |
| Region of Enrollment Estonia | 10 participants | 9 participants | 19 participants |
| Region of Enrollment Germany | 8 participants | 8 participants | 16 participants |
| Region of Enrollment Poland | 81 participants | 74 participants | 155 participants |
| Region of Enrollment South Africa | 73 participants | 71 participants | 144 participants |
| Region of Enrollment Sweden | 2 participants | 1 participants | 3 participants |
| Region of Enrollment United Kingdom | 6 participants | 7 participants | 13 participants |
| Region of Enrollment United States | 94 participants | 93 participants | 187 participants |
| Sex: Female, Male Female | 158 Participants | 146 Participants | 304 Participants |
| Sex: Female, Male Male | 116 Participants | 117 Participants | 233 Participants |
| Ulcer Duration | 206 days | 228 days | 214 days |
| Ulcer Size | 5.75 centimeters-squared | 5.90 centimeters-squared | 5.9 centimeters-squared |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 168 / 274 | 157 / 263 |
| serious Total, serious adverse events | 28 / 274 | 24 / 263 |
Outcome results
Primary
Complete Healing of the Study Ulcer by Week 16.
Time frame: 16 weeks
Population: Intent-to-Treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational Treatment (Dermagraft Plus Standard-of-Care) | Complete Healing of the Study Ulcer by Week 16. | 201 participants |
| Control (Standard-of-Care) | Complete Healing of the Study Ulcer by Week 16. | 176 participants |
Comparison: H0: the proportion of responders in the Dermagraft group = the proportion of responders in the Control group.~HA: the proportion of responders in the Dermagraft group ≠ the proportion of responders in the Control group.~The proportion of responders in the Dermagraft group was compared with the proportion of responders in the control group using the uncorrected chi-square test for 2x2 contingency tables. The difference between the groups was expected to be 13%.p-value: 0.103Chi-squared
Secondary
Time-to-Complete Healing
Kaplan-Meier survival analysis of the time to achieve median (50%) Complete Healing response in each treatment group.
Time frame: From Week 0 visit to date subject's completely healed ulcer is 1st recorded as healed. If subject's ulcer not healed at 16 weeks, the time until CH was censored at 112 days.
Population: Intent-to-Treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Investigational Treatment (Dermagraft Plus Standard-of-Care) | Time-to-Complete Healing | 58 days |
| Control (Standard-of-Care) | Time-to-Complete Healing | 64 days |
p-value: 0.4046Log Rank
Other Pre-specified
Complete Healing by Week 16: Ulcers <= 12 Months Duration
Time frame: 16 weeks
Population: Pre-specified Subgroup of the Intent-to-Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational Treatment (Dermagraft Plus Standard-of-Care) | Complete Healing by Week 16: Ulcers <= 12 Months Duration | 158 participants |
| Control (Standard-of-Care) | Complete Healing by Week 16: Ulcers <= 12 Months Duration | 132 participants |
Comparison: Pre-specified subgroup analysis of the primary endpointp-value: 0.0239Chi-squared