110 Bromelain-based Enzymatic Debridement of Large Burns

Abstract

Introduction

Bromelain based enzymatic debridement (BBED) is currently an investigational product in the US, however in Europe it has already been approved since 2012 for the treatment of deep thermal burns up to 15% TBSA and >3000 patients have been treated there since. Its growing use has lead to interest in the treatment of large burns. The objectives of this study were to assess the safety, efficacy and pharmacokinetic (PK) profile of BBED in patients with deep burns up to 30% TBSA.

Methods

A multi-center, open label, single-arm study was conducted in patients aged 4–70 years old suffering from 4–30% TBSA deep partial to full thickness thermal burns. Patients were treated with a 4 hour BBED application. In cases where the treated TBSA exceeded 15% or when the investigators elected to treat the burn area with 2 applications - a second application was performed immediately after the removal of the first application. Blood samples for a PK profile where obtained at 0, 2, 4, 12, 24 and 48 hours post BBED application in case of a single application, and at 0, 0.5, and 4 hours post 1^st BBED application and at 0.5, 4, 24 and 48 hours post 2^nd BBED application in case of 2 applications. Additional endpoints were investigated including safety, enzymatic debridement efficacy and time to complete eschar removal.

Results

Thirty-six patients were enrolled and treated with BBED, 22 with a single application and 14 with two applications, each up to 15% TBSA (mean dose 22.8gr, maximal dose of 60 gr). Complete eschar removal was achieved in 89% of cases, in an average of 0.83 days from enrollment (2.16 days from injury). The safety profile in patients treated up to 15% TBSA was comparable to that of patients treated between 15–30% TBSA, with no safety findings associated with increased TBSA or number of applications. PK profile in patients treated with 1 or 2 applications was found to be similar; BBED blood concentration reached Cmax by 2–4 hours and then declined with a mean T1/2 of 12 ± 4.4 hours. Quantifiable serum concentrations were measured through 48 hours after dose administration. BBED systemic exposure increases with dose and %TBSA, and a small increase in the average PK parameters was observed after the second application.

Conclusions

BBED use was shown to be safe and the efficacy results are consistent with previous studies. The pharmacokinetic profiles following 1^st and 2^nd topical applications were comparable, suggesting no concern with accumulation following a second topical application up to a total treatment area of 30% TBSA. A half-life of 12 hours implies additional applications may be possible 24–48 hours post initial applications, according to the TBSA treated, however this necessitates further trials.

Applicability of Research to Practice

The use of BBED in approved regions and future use in the US (pending authorization) appear to be safe up to 30% TBSA.