Leg Ulcer, Varicose Ulcer
Conditions
Keywords
wound, leg, venous, chronic, wound healing
Brief summary
This pilot study was designed to test the safety of Celaderm(TM) in treating venous leg ulcers and to give preliminary information about the efficacy of two different Celaderm(TM) dosing regimens.
Detailed description
Celaderm(TM) weekly for four weeks or biweekly for four treatments combined with Profore(R) compression vs. Profore(R) compression alone.
Interventions
DEVICECeladerm (Frozen Cultured Epidermal Allograft)
Four biweekly applications of Celaderm plus compression therapy
DEVICEControl (compression bandaging)
Multi-layer compression bandaging
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* venous ulcer \> 1 month and \< 12 months in duration; 2 to 20 sq cm in surface area; not infected * confirmatory venous ultrasound showing prior DVT and concurrent venous reflux * ankle-brachial index 0.80 or greater
Exclusion criteria
* cutaneous malignancy * recent treatment with corticosteroids or chemotherapeutic agents * wound exposed bone, tendon or neurovascular structure * wound infected and requiring antibiotics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Treatment Period, as Judged by the Investigator's Direct Observation. | 12 weeks | The primary efficacy observation was the proportion of wounds that achieved complete wound closure after 12 weeks of active treatment (i.e. of of Week 15 including screening/wash-in phase.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy: Proportion of Patients Achieving 90% Re-epithelialization After 12 Weeks of Active Treatment. | 12 Weeks | Re-epithelialization was judged by the Medical Monitor based upon computerized planimetry of serial wound photographs. |
| Secondary Efficacy: Durability of Wound Closure Through 12 Weeks After the End of the Treatment Period. | Variable - minimum of 12 weeks of follow-up. | The proportion of patients who had a recurrence of the study ulcer during follow-up after achieving wound closure during the active treatment period. |
| Secondary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Follow-up Period (24 Weeks). | 24 weeks | The proportion of patients achieving wound closure by the end of the study follow-up period, 90 days after the end of the active treatment period. |
Countries
United States
Participant flow
Recruitment details
An enrollment of 55 patients was planned to produce an expected yield of approximately 45 evaluable patients at up to nine study centers.
Pre-assignment details
72 patients were consented in this study. Eighteen failed screening: eight had HbA1c \> 7%; six failed wound size criteria; one was positive for HIV; one had a normal venous ultrasound; and two withdrew consent. Of the remaining 54 patients, 14 were not randomized: 11 healed \> 50% during screening; one had a severe AE; and two more withdrew.
Participants by arm
| Arm | Count |
|---|---|
| Group I - Weekly Celaderm Weekly topical applications of Celaderm, up to a maximum of four (4) applications, in combination with Adaptic and Profore four-layer compression dressing | 13 |
| Group II - Bi-weekly Celaderm Bi-weekly topical applications of Celaderm, up to a maximum of four (4) applications, in combination with Adaptic and Profore four-layer compression dressing | 15 |
| Group III - Control Adaptic and Profore four-layer compression dressing | 12 |
| Total | 40 |
Baseline characteristics
| Characteristic | Group II - Bi-weekly Celaderm | Group III - Control | Group I - Weekly Celaderm | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 7 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 9 Participants | 6 Participants | 29 Participants |
| Age, Continuous | 60.40 years STANDARD_DEVIATION 8.75 | 64 years STANDARD_DEVIATION 12.85 | 67.54 years STANDARD_DEVIATION 12.65 | 65.28 years STANDARD_DEVIATION 11.5 |
| Region of Enrollment United States | 15 Participants | 12 Participants | 13 Participants | 40 Participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 10 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 13 | 2 / 15 | 2 / 12 |
| serious Total, serious adverse events | 1 / 13 | 2 / 15 | 5 / 12 |
Outcome results
Primary
Primary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Treatment Period, as Judged by the Investigator's Direct Observation.
The primary efficacy observation was the proportion of wounds that achieved complete wound closure after 12 weeks of active treatment (i.e. of of Week 15 including screening/wash-in phase.)
Time frame: 12 weeks
Population: Intent-to-Treat population (i.e. all subjects randomized to treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I - Weekly Celaderm | Primary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Treatment Period, as Judged by the Investigator's Direct Observation. | 1 participants |
| Group II - Bi-weekly Celaderm | Primary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Treatment Period, as Judged by the Investigator's Direct Observation. | 4 participants |
| Group III - Control | Primary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Treatment Period, as Judged by the Investigator's Direct Observation. | 3 participants |
Secondary
Secondary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Follow-up Period (24 Weeks).
The proportion of patients achieving wound closure by the end of the study follow-up period, 90 days after the end of the active treatment period.
Time frame: 24 weeks
Population: Intent-to-Treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I - Weekly Celaderm | Secondary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Follow-up Period (24 Weeks). | 3 participants |
| Group II - Bi-weekly Celaderm | Secondary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Follow-up Period (24 Weeks). | 7 participants |
| Group III - Control | Secondary Efficacy: Cumulative Proportion of Patients Completely Healed by the End of the Follow-up Period (24 Weeks). | 5 participants |
Secondary
Secondary Efficacy: Durability of Wound Closure Through 12 Weeks After the End of the Treatment Period.
The proportion of patients who had a recurrence of the study ulcer during follow-up after achieving wound closure during the active treatment period.
Time frame: Variable - minimum of 12 weeks of follow-up.
Population: Intent-to-treat population achieving primary outcome
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I - Weekly Celaderm | Secondary Efficacy: Durability of Wound Closure Through 12 Weeks After the End of the Treatment Period. | 0 participants |
| Group II - Bi-weekly Celaderm | Secondary Efficacy: Durability of Wound Closure Through 12 Weeks After the End of the Treatment Period. | 1 participants |
| Group III - Control | Secondary Efficacy: Durability of Wound Closure Through 12 Weeks After the End of the Treatment Period. | 0 participants |
Secondary
Secondary Efficacy: Proportion of Patients Achieving 90% Re-epithelialization After 12 Weeks of Active Treatment.
Re-epithelialization was judged by the Medical Monitor based upon computerized planimetry of serial wound photographs.
Time frame: 12 Weeks
Population: Intent-to-Treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group I - Weekly Celaderm | Secondary Efficacy: Proportion of Patients Achieving 90% Re-epithelialization After 12 Weeks of Active Treatment. | 1 participants |
| Group II - Bi-weekly Celaderm | Secondary Efficacy: Proportion of Patients Achieving 90% Re-epithelialization After 12 Weeks of Active Treatment. | 5 participants |
| Group III - Control | Secondary Efficacy: Proportion of Patients Achieving 90% Re-epithelialization After 12 Weeks of Active Treatment. | 3 participants |