title: Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program.
abstract: The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds. The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care. Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts. A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=-1.1 days [95% CI, -1.5 to -0.7]; p<0.0001). This agreed with unblinded direct clinical assessment (difference=-2.1 days [95% CI, -2.7 to -1.5]; p<0.0001). Adverse events possibly related to treatment were mild or moderate and mostly at the application site. TBG accelerates re-epithelialization of partial thickness wounds compared to the current standard of care, providing a well-tolerated contribution to burn care in practice.
authors.affiliation: Department of Plastic Surgery and Burns, University Hospital Vall d'Hebron, Passeig de la Vall d'Hebron 119-129, 08035 Barcelona, Spain. Electronic address: jpbarret@vhebron.net.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Barret
authors.affiliation: Department of Oral and Maxillofacial Surgery/Plastic Surgery, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. DZ7, 17475 Greifswald, Germany. Electronic address: podmelle@uni-greifswald.de.
authors.forename: Fred
authors.initials: F
authors.lastname: Podmelle
authors.affiliation: Department for Burns and Reconstructive Surgery, University Hospital Brno, Jihlavská 20, Brno, Czech Republic.
authors.forename: Břetislav
authors.initials: B
authors.lastname: Lipový
authors.affiliation: Division of Plastic and Aesthetic Surgery, Burn Surgery, Klinikum Leverkusen, Am Gesundheitspark 11, 51375 Leverkusen, Germany.
authors.forename: Hans-Oliver
authors.initials: HO
authors.lastname: Rennekampff
authors.affiliation: Catholic University of Applied Sciences, Karlstrasse 36, 79104 Freiburg, Germany; Department of Dermatology, University Medical Center Freiburg, Hauptstrasse 7, 79104 Freiburg, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Schumann
authors.affiliation: Department of Pediatric Dermatology, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland.
authors.forename: Agnes
authors.initials: A
authors.lastname: Schwieger-Briel
authors.affiliation: Birken AG (An Amryt Pharma Company), Streiflingsweg 11, 75223 Niefern-Öschelbronn, Germany.
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Zahn
authors.affiliation: Department of Oral and Maxillofacial Surgery/Plastic Surgery, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. DZ7, 17475 Greifswald, Germany.
authors.forename: Hans-Robert
authors.initials: HR
authors.lastname: Metelmann
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D002056:Burns / Q000628:therapy*; D005260:Female; D005782:Gels / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062326:Re-Epithelialization; D016038:Skin Transplantation; D000072836:Surgical Wound / Q000188:drug therapy*; D016896:Treatment Outcome; D014315:Triterpenes / Q000627:therapeutic use*; D000094062:Betulinic Acid
chemical_list: D005782:Gels; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid
keywords: Intra-individual comparison; Split thickness skin graft; Topical betulin gel; Wound closure; Wound healing