Effects of Therapy With Sulfamylon® 5% Topical Solution Compared to a Historical Control Group

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).

• Sulfamylon® For 5 % Topical Solution (Drug), also known as mafenide acetate: 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 (Drug), also known as Bacitracin; Amphotericin B; others noted below.: 'Topical Antimicrobial/Antifungal Medications' Various topical antimicrobials and antifungals include: Bacitracin; Amphotericin B; Silver Sulfadiazine; Cefazolin; Vancomycin; Nystatin; Fluconazole; Piperacillin Sodium with Tazobactam.

Primary outcomes

• 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 outcomes

• 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 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 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.
• 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.

Sex: All, ages: 3 Months to any

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

Participant flow

Outcome results

• Percentage of Participants With Graft Loss After Initial Meshed Autograft Procedure on Days 5-7. (Primary), Number, Percentage of Participants: Historical Control 4.9; Prospective Patients/Active Drug 4.3
• Percentage of Participants With All-cause Graft Loss at Days 12 to 14 in the FAS Population (Secondary), Number, Percentage of participants: Historical Control 20.3; Prospective Patients/Active Drug 2.7
• Percentage of Participants With All-cause Graft Loss at Days 18 to 21 in the FAS Population (Secondary), Number, Percentage of participants: Historical Control 4.5; Prospective Patients/Active Drug 6
• Percentage of Participants With Treatment Failure at Days 5 to 7 in the FAS Population (Secondary), Number, Percentage of participants: Historical Control 13.4; Prospective Patients/Active Drug 1.4
• Percentage of Participants With Infectious Graft Loss at Days 5 to 7 in the FAS Population (Secondary), Number, Percentage of participants: Historical Control 2.4; Prospective Patients/Active Drug 0.7
• Percentage of Participants With Infectious Graft Loss at Days 12 to 14 in the FAS Population (Secondary), Number, Percentage of participants: Historical Control 3.4; Prospective Patients/Active Drug 0.0
• Percentage of Participants With Infectious Graft Loss at Days 18 to 21 in the FAS Population (Secondary), Number, Percentage of participants: Historical Control 0.0; Prospective Patients/Active Drug 1.3

Adverse events

Serious adverse events by term

Other adverse events by term

Limitations and caveats: The study was terminated on 17 June 2013 due to the recommendation and request by the FDA to design a superiority clinical study to satisfy the sponsor's post marketing study commitment for SS5%.

• Eric Davis, MD, Study director, Mylan Inc.