Elliott Bennett-Guerrero1, Scott M Berry2, Sergio D Bergese3, Phillip R Fleshner4, Harold S Minkowitz5, Alvaro M Segura-Vasi6, Kamal M F Itani7, Karen W Henderson8, Felicia P Rackowski9, Laura H Aberle8, Martin E Stryjewski10, G Ralph Corey8, Kent S Allenby9. 1. Duke Clinical Research Institute, Duke University, Durham, NC, USA. Electronic address: Elliott.Bennett-Guerrero@stonybrookmedicine.edu. 2. CRC of Jackson, Jackson, MS, USA. 3. The Ohio State University Medical Center, Columbus, OH, USA. 4. Cedars-Sinai Medical Center, Los Angeles, CA, USA. 5. Memorial Hermann Memorial City Medical Center, Houston, TX, USA. 6. Shoals Clinical Research Associates, LLC, Florence, AL, USA. 7. V.A. Boston Healthcare System, Boston University and Harvard Medical School, Boston, MA, USA. 8. Duke Clinical Research Institute, Duke University, Durham, NC, USA. 9. Dr. Reddy's Laboratories, Inc., Princeton, NJ, USA. 10. Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires, Argentina.
Abstract
BACKGROUND: SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. STUDY DESIGN: In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. RESULTS: Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). CONCLUSION: In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. SUMMARY:Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI.
RCT Entities:
BACKGROUND: SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. STUDY DESIGN: In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. RESULTS: Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). CONCLUSION: In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. SUMMARY:Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI.
Authors: Gill Norman; Ross A Atkinson; Tanya A Smith; Ceri Rowlands; Amber D Rithalia; Emma J Crosbie; Jo C Dumville Journal: Cochrane Database Syst Rev Date: 2017-10-30
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Authors: O Zmora; Y Stark; O Belotserkovsky; M Reichert; G A Kozloski; N Wasserberg; H Tulchinsky; L Segev; A J Senagore; N Emanuel Journal: Tech Coloproctol Date: 2022-09-01 Impact factor: 3.699