(CR-021) Comparison of Bromelain-Based Enzymatic Debridement to Collagenase SANTYL® Ointment - Analysis from the ChronEx Multicenter RCT

Keren David, MSc; Asi Haviv, DMD; Yael Katz-Levy, PhD; Ety Klinger, PhD, MBA; Felix Sigal, DPM; Robert Snyder, DPM, MBA, MSc

Introduction:

ChronEx, a multicenter randomized controlled trial, previously demonstrated that a novel bromelain-based enzymatic debridement (BBD) was superior to hydrogel placebo and non-surgical standard of care (NSSOC) in achieving complete debridement (CD) and complete granulation (CG), core components of wound bed preparation (WBP) for chronic venous leg ulcers (VLU). Collagenase SANTYL® Ointment, one of the permitted NSSOC treatments, is an FDA-approved agent indicated for debriding chronic dermal ulcers. This post hoc analysis evaluates the efficacy of BBD compared with SANTYL in the VLU subgroup of ChronEx.

Methods: Patients with chronic VLU were randomized 3:3:2 to daily BBD, placebo, or NSSOC for up to 14 days or until CD, followed by weekly NSSOC through 12 weeks. NSSOC included SANTYL, hydrogels, medical-grade honey, and non-active dressings; surgical or mechanical debridement was not allowed. Post hoc analyses assessed incidence and time to CD, CG, and WBP (defined as achieving both), comparing BBD with SANTYL, placebo, and NSSOC excluding SANTYL (NSSOCES). CD and CG were evaluated clinically. Time-to-event differences were tested with log-rank tests, and incidences with Fisher exact tests.

Results:

Among 119 randomized patients, 46 received BBD, 43 placebo, and 30 NSSOC (8 SANTYL; 22 NSSOCES). Baseline characteristics were comparable across groups.

Median time to CD was 9 days (95% CI 5–15) for BBD versus not achieved for SANTYL (22–NA, P = 0.023), 63 days (21–93) for placebo, and 44 days (21–67) for NSSOCES.
Incidence of CD within 2 weeks was 63.0% (47.5–76.8) for BBD versus 0% for SANTYL (P = 0.001), 30.2% (17.2–46.1) for placebo, and 18.2% (5.2–40.3) for NSSOCES.

Median time to CG and to WBP was 11 days (95% CI 7–50) for BBD versus not achieved for SANTYL (22–NA, P = 0.014), 85 days (24–99) for placebo, and 61 days (30–85) for NSSOCES.
Incidence of WBP was 78.3% (63.6–89.1) for BBD versus 37.5% (8.5–75.5) for SANTYL (P = 0.03), 60.5% (44.4–75.0) for placebo, and 68.2% (45.1–86.1) for NSSOCES.

Discussion: This post hoc analysis demonstrates that BBD outperforms SANTYL in accelerating CD, CG, and overall WBP, and in improving the incidence of WBP. These findings reinforce BBD as an effective modality for optimizing wound bed preparation in chronic VLU.