Prophylaxis of Wound Infections- Antibiotics in Renal Donation (POWAR): A Multicentre UK Double Blinded Placebo Controlled Randomised Trial

Abstract

Background: Postoperative infection following hand assisted laparoscopic donor nephrectomy (HALDN) confers significant morbidity to a healthy patient group. Current UK guidelines cite a lack of evidence for routine antibiotic prophylaxis. This trial assessed if a single preoperative antibiotic dose could reduce post HALDN infections. Methods: Eligible donors were randomly and blindly allocated to preoperative single dose intravenous co-amoxiclav or saline. The primary composite endpoint was clinical evidence of any postoperative infection at 30 days including surgical site infection (SSI), urinary tract infection (UTI) and lower respiratory tract infection (LRTI). The study aimed to detect a 10% or greater reduction in the primary endpoint with 90% power (α 0·05). All analyses were by intention to treat (ITT). Findings: 293 participants underwent HALDN (148 antibiotic arm and 145 placebo arm). 99% (291 of 293) completed follow up. The total infection rate was 40.7% (59 of 145) in the placebo group and 23% (34 of 148) in the antibiotic group (p=0·001). Superficial SSIs were 20·7% (30 of 145 patients) in the placebo group vs 10.1% (15 of 148 patients) in the antibiotic group (p=0·012). LRTIs were 9% (13 of 145) in the placebo group and 3.4% (5 of 148) in the antibiotic group (p=0.046). UTIs were 4.1% (6 of 145) in the placebo group and 3.4% (5 of 148) in the antibiotic group (p=0.72). Reportable adverse events occurred in 22 patients per group (14·7% (antibiotic) vs 15·2% (placebo), p=0·54). Antibiotic prophylaxis conferred a 17.7% (95% CI 7.2–28.1%), absolute risk reduction (ARR) in developing postoperative infection, with 6 donors requiring treatment (NNT) to prevent one infection. Interpretation: Single dose preoperative antibiotic prophylaxis dramatically reduces post HALDN infection rates, mainly impacting SSIs and LRTIs. Trial Registration Number: Trial registration was with the European Union clinical trials register, no 2012-000942-36. Funding Statement: National Institute for Health Research (Project Number PB-PG-1010-23108). Declaration of Interests: We declare the authors have no competing interests. Ethics Approval Statement: Ethical approval for the study was granted by the London Harrow Research Ethics Committee and regulatory approval by the Medicines and Healthcare Products Regulatory Agency (MHRA). All subjects provided written consent.