Burns
Conditions
Keywords
Second Degree Burn Injuries
Brief summary
This is a randomized, within-patient controlled study to compare the clinical performance of the ReCell Device with that of Split-thickness Meshed Skin Grafts for the treatment of second degree burns. The hypothesis to be supported are: 1) non-inferiority with the primary efficacy endpoint defined as recipient site wound closure at week 4 follow-up visit of the ReCell-treated area as compared to that of the STMSG-treated area, and 2)superiority in the healing of the ReCell donor site as compared to the STMSG donor site at week 1.
Interventions
DEVICEReCell and Split-thickness skin graft
The surgeon will be required to select two similar non-contiguous injury areas with both areas being at least 100cm2 and second degree depth/severity. One area will be treated using ReCell and the second using Split-thickness Skin Graft.
Sponsors
United States Department of Defense
Royal Perth Hospital
MedDRA Assistance Inc
BioStat International, Inc.
Avita Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The subject requires primary skin grafting as a result of an acute thermal burn injury * The area of the burn injury is at least 200cm2 (1% TBSA in adults) if a contiguous wound, or at least 100cm2 for each of 2 noon-contiguous wounds * The area of total burn injury is 1-20% TBSA * The burn injured area can be divided into two treatment areas ( control and treatment) with 100-320cm2 area for each treatment type * The study treatment area is a second degree burn injury * The subject is between 18-65 years of age * The subject is willing to complete all follow-up evaluations required by the study protocol * The subject is to abstain from any other treatment of the wound(s) for the duration of the study unless medically necessary * The subject agrees to abstain from enrollment in any other clinical trial for the duration of the study * The subject and/or guardian are able to read and understand instructions and give informed, voluntary, written consent * The subject is able and willing to follow the protocol requirements
Exclusion criteria
* The subject's burn injuries were caused by chemicals, electricity, and/or radioactive substances * The total subject burn injury is less than 1% or more than 20% TBSA * The subject has a microbiologically proven pre-existing local or systemic bacterial infection * The subject has been receiving a systemic antibiotic for more than 48 hours prior to grafting * The subject is known to have a pre-existing condition that may interfere with wound healing ( e.g. malignancy, diabetes, or autoimmune disease) * The subject is unable to follow the protocol * The subject is taking medication known to have an effect on wound healing or skin pigmentation ( e.g. systemic corticosteroids, retinoids, etc) * The subject has other concurrent conditions that in the opinion of the investigator may compromise patient safety or study objectives * The subject has a known hypersensitivity to Trypsin or Compound sodium Lactate for Irrigation (Hartmann's) solution
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority) | 4 weeks | Recipient site wound closure for both ReCell and STMSG will be defined as the presence of \>=95% epithelialization with contiguous layer of viable epithelium without the need for secondary surgical intervention. Factors considered during the assessment included color, presence of granulation tissue, and whether or not the entire wound is covered with a contiguous layer of viable epithelium. Using this definition, some small degree of punctate blistering was acceptable as long as the wound was \>=95% epithelialized. |
| Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority) | 1 week | Donor site healing will be considered as complete (100%) wound closure if the following criteria were met: an ability to separate the dressing from the wound bed with visible presence over the entirety of the wound of dry, opalescent-pink external surface representing the newly formed outer cornfield layer of the epidermis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Epithelialization at Each Visit Through Week 16 | Each visit through Week 16 | The percent epithelialization of the RECELL and Control treated sites will be assessed using standardized planimetry/tracing procedures. The tracings were uploaded to a Central Reading Facility for calculation of percent epithelialization using a computerized measurement technique. |
| Wound Closure at Week 2 (Based on Investigators Assessment) | Week 2 | The proportion of recipient sites achieving wound closure at Week 2 was evaluated using the Investigators assessment of wound healing. |
| Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Pain (Weeks 1-16) and Appearance (Weeks 16-52) | Subject assessment of pain at the RECELL and Control recipient sites was performed at all study follow-up visits up to Week 16. Subjects also assessed the satisfaction with the appearance of the treatment sites at the Week 16, 24, and 52 study follow-up visits. The subject assessments were performed using VAS (visual analogue scale) style questionnaires. Pain VAS 0-100 where 0=non-existent pain and 100=severe pain. Appearance VAS 0-100 where 0=terrible and 100=exceptional |
| Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Pain (Weeks 1-16) and Appearance (Weeks 16-52) | Subject assessment of pain at the RECELL and Control donor sites was performed at all study follow-up visits up to Week 16. Subjects also assessed the satisfaction with the appearance of the donor sites at the Week 16, 24, and 52 study follow-up visits. The subject assessments were performed using VAS (visual analogue scale) style questionnaires. Pain VAS 0-100 where 0=non-existent pain and 100=severe pain. Appearance VAS 0-100 where 0=terrible and 100=exceptional. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental: All Participants (Within Patient Control) Every subject received both interventions (RECELL and 2:1 meshed split-thickness autograft). Two distinct but similar areas of burn injury at least 100 cm2 and second degree depth will be treated according to random assignment (Area A and Area B). One burn injury area receives RECELL (Investigational Treatment) and the other area 2:1 meshed autograft (Control). | 101 |
| Total | 101 |
Baseline characteristics
| Characteristic | Experimental: All Participants (Within Patient Control) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 101 Participants |
| Age, Continuous | 39.5 years STANDARD_DEVIATION 13.06 |
| Race/Ethnicity, Customized Race American Indian | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants |
| Race/Ethnicity, Customized Race Black | 20 Participants |
| Race/Ethnicity, Customized Race Hispanic | 19 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants |
| Race/Ethnicity, Customized Race White | 59 Participants |
| Region of Enrollment United States | 101 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 101 |
| serious Total, serious adverse events | 10 / 101 |
Outcome results
Primary
Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority)
Donor site healing will be considered as complete (100%) wound closure if the following criteria were met: an ability to separate the dressing from the wound bed with visible presence over the entirety of the wound of dry, opalescent-pink external surface representing the newly formed outer cornfield layer of the epidermis.
Time frame: 1 week
Population: Analysis was performed on ITT, PP, and MPP populations. Note: The number of participants with evaluable donor sites differs than number of participants with evaluable recipient sites.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RECELL | Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority) | Intent to Treat (ITT) | 22 Participants |
| RECELL | Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority) | Per Protocol (PP) | 19 Participants |
| RECELL | Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority) | Modified Per Protocol (MPP) | 18 Participants |
| Control | Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority) | Intent to Treat (ITT) | 10 Participants |
| Control | Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority) | Per Protocol (PP) | 10 Participants |
| Control | Incidence of RECELL Donor Site Healing Compared to Control at 1 Week (Superiority) | Modified Per Protocol (MPP) | 10 Participants |
Primary
Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority)
Recipient site wound closure for both ReCell and STMSG will be defined as the presence of \>=95% epithelialization with contiguous layer of viable epithelium without the need for secondary surgical intervention. Factors considered during the assessment included color, presence of granulation tissue, and whether or not the entire wound is covered with a contiguous layer of viable epithelium. Using this definition, some small degree of punctate blistering was acceptable as long as the wound was \>=95% epithelialized.
Time frame: 4 weeks
Population: Analysis to evaluate non-inferiority of recipient site wound closure was performed on the ITT, PP, and MPP populations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RECELL | Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority) | Per Protocol Population (PP) | 82 Participants |
| RECELL | Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority) | Modified Per Protocol Population (MPP) | 82 Participants |
| RECELL | Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority) | Intent to Treat (ITT) | 84 Participants |
| Control | Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority) | Per Protocol Population (PP) | 87 Participants |
| Control | Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority) | Modified Per Protocol Population (MPP) | 83 Participants |
| Control | Incidence of RECELL-treated Area Closure Compared to Control at 4 Weeks (Non-inferiority) | Intent to Treat (ITT) | 97 Participants |
Secondary
Mean Pain and Appearance Scores at Donor Sites (Subject Assessment)
Subject assessment of pain at the RECELL and Control donor sites was performed at all study follow-up visits up to Week 16. Subjects also assessed the satisfaction with the appearance of the donor sites at the Week 16, 24, and 52 study follow-up visits. The subject assessments were performed using VAS (visual analogue scale) style questionnaires. Pain VAS 0-100 where 0=non-existent pain and 100=severe pain. Appearance VAS 0-100 where 0=terrible and 100=exceptional.
Time frame: Pain (Weeks 1-16) and Appearance (Weeks 16-52)
Population: Per-Protocol Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 2 | 5.1 Scores on a Scale (0-100) | Standard Deviation 11.25 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 16 | 0.9 Scores on a Scale (0-100) | Standard Deviation 1.61 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 4 | 1.9 Scores on a Scale (0-100) | Standard Deviation 5.84 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Visual Appearance Week 16 | 89.8 Scores on a Scale (0-100) | Standard Deviation 16.87 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 3 | 1.9 Scores on a Scale (0-100) | Standard Deviation 3.87 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Visual Appearance Week 24 | 93.4 Scores on a Scale (0-100) | Standard Deviation 9.96 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 8 | 1.4 Scores on a Scale (0-100) | Standard Deviation 2.78 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Visual Appearance Week 52 | 91.2 Scores on a Scale (0-100) | Standard Deviation 14.84 |
| RECELL | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 1 | 21.9 Scores on a Scale (0-100) | Standard Deviation 26.35 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Visual Appearance Week 52 | 83.3 Scores on a Scale (0-100) | Standard Deviation 18.62 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 1 | 43.5 Scores on a Scale (0-100) | Standard Deviation 29.43 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 2 | 19.3 Scores on a Scale (0-100) | Standard Deviation 24.42 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 3 | 9.4 Scores on a Scale (0-100) | Standard Deviation 19.14 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 4 | 5.2 Scores on a Scale (0-100) | Standard Deviation 12.07 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 8 | 3.7 Scores on a Scale (0-100) | Standard Deviation 9.97 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Pain Scores at Week 16 | 1.5 Scores on a Scale (0-100) | Standard Deviation 2.84 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Visual Appearance Week 16 | 75.1 Scores on a Scale (0-100) | Standard Deviation 26.36 |
| Control | Mean Pain and Appearance Scores at Donor Sites (Subject Assessment) | Mean Visual Appearance Week 24 | 81.1 Scores on a Scale (0-100) | Standard Deviation 21.55 |
Secondary
Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment)
Subject assessment of pain at the RECELL and Control recipient sites was performed at all study follow-up visits up to Week 16. Subjects also assessed the satisfaction with the appearance of the treatment sites at the Week 16, 24, and 52 study follow-up visits. The subject assessments were performed using VAS (visual analogue scale) style questionnaires. Pain VAS 0-100 where 0=non-existent pain and 100=severe pain. Appearance VAS 0-100 where 0=terrible and 100=exceptional
Time frame: Pain (Weeks 1-16) and Appearance (Weeks 16-52)
Population: Per-Protocol Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 2 | 12.4 Scores on a Scale (0-100) | Standard Deviation 19.42 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 16 | 3.3 Scores on a Scale (0-100) | Standard Deviation 8.15 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 4 | 6.9 Scores on a Scale (0-100) | Standard Deviation 12.64 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Visual Appearance Week 16 | 77.7 Scores on a Scale (0-100) | Standard Deviation 23.96 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 3 | 9.6 Scores on a Scale (0-100) | Standard Deviation 14.39 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Visual Appearance Week 24 | 82.6 Scores on a Scale (0-100) | Standard Deviation 22.82 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 8 | 7.6 Scores on a Scale (0-100) | Standard Deviation 16.94 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Visual Appearance Week 52 | 83.1 Scores on a Scale (0-100) | Standard Deviation 22.07 |
| RECELL | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 1 | 24.1 Scores on a Scale (0-100) | Standard Deviation 23.31 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Visual Appearance Week 52 | 80.1 Scores on a Scale (0-100) | Standard Deviation 19.73 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 1 | 26.5 Scores on a Scale (0-100) | Standard Deviation 24.58 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 2 | 12.4 Scores on a Scale (0-100) | Standard Deviation 19.1 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 3 | 7.9 Scores on a Scale (0-100) | Standard Deviation 14.6 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 4 | 6.7 Scores on a Scale (0-100) | Standard Deviation 12.25 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 8 | 8.8 Scores on a Scale (0-100) | Standard Deviation 18.46 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Pain Scores at Week 16 | 4.3 Scores on a Scale (0-100) | Standard Deviation 10.56 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Visual Appearance Week 16 | 75.6 Scores on a Scale (0-100) | Standard Deviation 24.18 |
| Control | Mean Pain and Appearance Scores at RECELL and Control Recipient Sites (Subject Assessment) | Mean Visual Appearance Week 24 | 79.4 Scores on a Scale (0-100) | Standard Deviation 22.78 |
Secondary
Percent of Epithelialization at Each Visit Through Week 16
The percent epithelialization of the RECELL and Control treated sites will be assessed using standardized planimetry/tracing procedures. The tracings were uploaded to a Central Reading Facility for calculation of percent epithelialization using a computerized measurement technique.
Time frame: Each visit through Week 16
Population: Percent Epithelialization presented for Per Protocol Population (PP) based on subjects presented for healing evaluation per visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RECELL | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 1 | 66.1 percentage of epithelialization | Standard Deviation 40.94 |
| RECELL | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 2 | 92.1 percentage of epithelialization | Standard Deviation 20.38 |
| RECELL | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 3 | 95.8 percentage of epithelialization | Standard Deviation 14.9 |
| RECELL | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 4 | 97.7 percentage of epithelialization | Standard Deviation 11.98 |
| RECELL | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 8 | 99.8 percentage of epithelialization | Standard Deviation 1.42 |
| RECELL | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 16 | 100.0 percentage of epithelialization | Standard Deviation 0 |
| Control | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 8 | 100.0 percentage of epithelialization | Standard Deviation 0 |
| Control | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 1 | 74.0 percentage of epithelialization | Standard Deviation 41.25 |
| Control | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 4 | 100.0 percentage of epithelialization | Standard Deviation 0.07 |
| Control | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 2 | 99.8 percentage of epithelialization | Standard Deviation 1.16 |
| Control | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 16 | 100.0 percentage of epithelialization | Standard Deviation 0 |
| Control | Percent of Epithelialization at Each Visit Through Week 16 | % Epithelialization - Week 3 | 99.9 percentage of epithelialization | Standard Deviation 0.58 |
Secondary
Wound Closure at Week 2 (Based on Investigators Assessment)
The proportion of recipient sites achieving wound closure at Week 2 was evaluated using the Investigators assessment of wound healing.
Time frame: Week 2
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RECELL | Wound Closure at Week 2 (Based on Investigators Assessment) | RECELL and Control Healed | 70 Participants |
| RECELL | Wound Closure at Week 2 (Based on Investigators Assessment) | RECELL Healed and Control Not Healed | 1 Participants |
| RECELL | Wound Closure at Week 2 (Based on Investigators Assessment) | RECELL Not Healed and Control Healed | 16 Participants |
| RECELL | Wound Closure at Week 2 (Based on Investigators Assessment) | RECELL and Control Not Healed | 0 Participants |