Burns
Conditions
Keywords
thermal injuries, burns, Burn Patients
Brief summary
The primary objective is to compare the effectiveness of treatment with Sulfamylon® solution as the initial topical moist dressing over meshed autografts following the initial graft procedure on preventing graft loss in a prospective cohort of subjects versus a historical control group in a non-inferiority trial.
Detailed description
This is a prospective, non-inferiority, multi-center, historically controlled, open label study that will evaluate the effects of topical therapy with Sulfamylon® For 5% Topical Solution on autograft healing in subjects with thermal injuries requiring meshed autografts against a similar historic control population in which Sulfamylon® For 5% Topical Solution or mafenide acetate or other mafenide salt forms were not used. Prospective subjects meeting the entrance criteria will receive Sulfamylon® solution as topical antimicrobial treatment on moist dressings following initial meshed autograft procedure (Day 1). Sulfamylon® solution will be used every 6-8 hours, or as needed, to keep the dressing moist. The graft will be evaluated on Days 5-7, Days 12-14 and Days 18-21, unless the subject is discharged, dies, or experiences graft loss / regrafting of the initial meshed autograft prior to Assessment 4 (Days 18-21).
Interventions
DRUGSulfamylon® For 5 % Topical Solution
Sulfamylon® For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds.
'Topical Antimicrobial/Antifungal Medications' Various topical antimicrobials and antifungals include: Bacitracin; Amphotericin B; Silver Sulfadiazine; Cefazolin; Vancomycin; Nystatin; Fluconazole; Piperacillin Sodium with Tazobactam.
Sponsors
Mylan Bertek Pharmaceuticals
Mylan Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to No maximum
Healthy volunteers
No
Inclusion criteria
In order for prospective subjects to be eligible for entry into the study: * Subjects must have thermal injuries of 20-60% TBSA requiring at least one meshed autograft on the chest, abdomen, or proximal upper and lower extremities following surgical excision of the burn injury. Refer to Supplement 20.3.2: Lund Browder charts * Subjects may be male or female, 3 months of age or older * Females of childbearing potential must have a negative urine pregnancy test upon admission and agree to avoid pregnancy throughout the course of the study. Since this population is hospitalized for the duration of the study, an agreement of sexual abstinence is appropriate for this trial. Those subjects who do not wish to commit to sexual abstinence for the duration of this study must agree to avoid pregnancy by using a medically supervised method of contraception (such as hormonal contraception in conjunction with a vaginal spermicide or a tubal ligation at least 3 months prior to study entry) * Subjects must be willing and able to provide written informed consent. If subjects are unable to provide written informed consent, then the subject's legally acceptable representative may provide written informed consent in accordance with the IRB/IEC, and federal, state and local regulations.
Exclusion criteria
Prospective subjects will be excluded from the study for the following reasons: * Non-thermal burn injuries * Inhalation injuries resulting in a PaO2 /FIO2 ratio \< 300 mmHg on more than one arterial blood gas in the first 48 hours post-admission * Females who are currently pregnant or breast feeding, or who intend to become pregnant during the course of the study * Subjects with acute renal failure * Subjects with known systemic allergy to sulfonamides or to sulfur-containing medication * Time interval between burn injury and excision and grafting is greater than 7 days * Grafting procedures that are conducted and/or evaluated on an outpatient basis * Inability to use a meshed autograft as part of the initial grafting procedure * Inability to use SS5% as the only initial prophylactic topical antimicrobial therapy on meshed autografts * Thermal burn injuries less than 20% or greater than 60% TBSA * Subjects who are participating in any other clinical studies involving any investigational product, or who have participated in such a study within the previous 30 days * Subjects with known glucose-6-phosphate dehydrogenase deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Graft Loss After Initial Meshed Autograft Procedure on Days 5-7. | The primary analysis will compare the percent of subjects with All Cause Graft Loss of the initial meshed autograft procedure at Days 5-7. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With All-cause Graft Loss at Days 18 to 21 in the FAS Population | Days 18 to 21 | All cause graft loss is defined as graft adhesion of \< 85% for the initial meshed autograft procedure. |
| Percentage of Participants With Treatment Failure at Days 5 to 7 in the FAS Population | Days 5-7 | Treatment failure is defined as a change in topical antimicrobial therapy of initial meshed autograft due to suspected infection within the first 7 days or infectious graft loss. |
| Percentage of Participants With All-cause Graft Loss at Days 12 to 14 in the FAS Population | Secondary analyses will include the percent of subjects with All Cause Graft Loss at Days 12-14 | All cause graft loss is defined as graft adhesion of \< 85% for the initial meshed autograft procedure. |
| Percentage of Participants With Infectious Graft Loss at Days 12 to 14 in the FAS Population | Days 12-14 | Graft adhesion of \< 85% for the initial meshed autograft procedure due to infection. |
| Percentage of Participants With Infectious Graft Loss at Days 18 to 21 in the FAS Population | Days 18-21 | Graft adhesion of \< 85% for the initial meshed autograft procedure due to infection. |
| Percentage of Participants With Infectious Graft Loss at Days 5 to 7 in the FAS Population | Days 5-7 | Graft adhesion of \< 85% for the initial meshed autograft procedure due to infection. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Historical Control Treated within the last 5 years (if possible) with topical prophylactic therapies that did not include mafenide acetate or mafenide salt forms (with the sponsor's prior approval, sites may obtain historical control subjects treated longer than 5 years ago)
Sulfamylon® (mafenide acetate) For 5 % Topical Solution: Sulfamylon® For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds. | 82 |
| Prospective Patients/Active Drug Prospective subjects with thermal injuries of 20-60% TBSA on the chest, abdomen, or proximal upper and lower extremities requiring meshed autografts on these areas will receive SS5% as the initial topical moist dressing over the meshed autograft(s) placed at the initial graft procedure (Day 1).
Sulfamylon® (mafenide acetate) For 5 % Topical Solution: Sulfamylon® For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds. | 138 |
| Total | 220 |
Baseline characteristics
| Characteristic | Historical Control | Prospective Patients/Active Drug | Total |
|---|---|---|---|
| Age, Continuous | 38.9 years STANDARD_DEVIATION 18.91 | 44.7 years STANDARD_DEVIATION 17.87 | 42.6 years STANDARD_DEVIATION 18.44 |
| Age, Customized <18 years | 11 participants | 5 participants | 16 participants |
| Age, Customized >= 18 years | 71 participants | 133 participants | 204 participants |
| Region of Enrollment United States | 82 participants | 138 participants | 220 participants |
| Sex/Gender, Customized Female | 19 participants | 29 participants | 48 participants |
| Sex/Gender, Customized Male | 63 participants | 109 participants | 172 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 74 / 82 | 130 / 138 |
| serious Total, serious adverse events | 9 / 82 | 27 / 138 |
Outcome results
Primary
Percentage of Participants With Graft Loss After Initial Meshed Autograft Procedure on Days 5-7.
Time frame: The primary analysis will compare the percent of subjects with All Cause Graft Loss of the initial meshed autograft procedure at Days 5-7.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Historical Control | Percentage of Participants With Graft Loss After Initial Meshed Autograft Procedure on Days 5-7. | 4.9 Percentage of Participants |
| Prospective Patients/Active Drug | Percentage of Participants With Graft Loss After Initial Meshed Autograft Procedure on Days 5-7. | 4.3 Percentage of Participants |
Secondary
Percentage of Participants With All-cause Graft Loss at Days 12 to 14 in the FAS Population
All cause graft loss is defined as graft adhesion of \< 85% for the initial meshed autograft procedure.
Time frame: Secondary analyses will include the percent of subjects with All Cause Graft Loss at Days 12-14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Historical Control | Percentage of Participants With All-cause Graft Loss at Days 12 to 14 in the FAS Population | 20.3 Percentage of participants |
| Prospective Patients/Active Drug | Percentage of Participants With All-cause Graft Loss at Days 12 to 14 in the FAS Population | 2.7 Percentage of participants |
Secondary
Percentage of Participants With All-cause Graft Loss at Days 18 to 21 in the FAS Population
All cause graft loss is defined as graft adhesion of \< 85% for the initial meshed autograft procedure.
Time frame: Days 18 to 21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Historical Control | Percentage of Participants With All-cause Graft Loss at Days 18 to 21 in the FAS Population | 4.5 Percentage of participants |
| Prospective Patients/Active Drug | Percentage of Participants With All-cause Graft Loss at Days 18 to 21 in the FAS Population | 6 Percentage of participants |
Secondary
Percentage of Participants With Infectious Graft Loss at Days 12 to 14 in the FAS Population
Graft adhesion of \< 85% for the initial meshed autograft procedure due to infection.
Time frame: Days 12-14
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Historical Control | Percentage of Participants With Infectious Graft Loss at Days 12 to 14 in the FAS Population | 3.4 Percentage of participants |
| Prospective Patients/Active Drug | Percentage of Participants With Infectious Graft Loss at Days 12 to 14 in the FAS Population | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Infectious Graft Loss at Days 18 to 21 in the FAS Population
Graft adhesion of \< 85% for the initial meshed autograft procedure due to infection.
Time frame: Days 18-21
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Historical Control | Percentage of Participants With Infectious Graft Loss at Days 18 to 21 in the FAS Population | 0.0 Percentage of participants |
| Prospective Patients/Active Drug | Percentage of Participants With Infectious Graft Loss at Days 18 to 21 in the FAS Population | 1.3 Percentage of participants |
Secondary
Percentage of Participants With Infectious Graft Loss at Days 5 to 7 in the FAS Population
Graft adhesion of \< 85% for the initial meshed autograft procedure due to infection.
Time frame: Days 5-7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Historical Control | Percentage of Participants With Infectious Graft Loss at Days 5 to 7 in the FAS Population | 2.4 Percentage of participants |
| Prospective Patients/Active Drug | Percentage of Participants With Infectious Graft Loss at Days 5 to 7 in the FAS Population | 0.7 Percentage of participants |
Secondary
Percentage of Participants With Treatment Failure at Days 5 to 7 in the FAS Population
Treatment failure is defined as a change in topical antimicrobial therapy of initial meshed autograft due to suspected infection within the first 7 days or infectious graft loss.
Time frame: Days 5-7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Historical Control | Percentage of Participants With Treatment Failure at Days 5 to 7 in the FAS Population | 13.4 Percentage of participants |
| Prospective Patients/Active Drug | Percentage of Participants With Treatment Failure at Days 5 to 7 in the FAS Population | 1.4 Percentage of participants |