Comparative Effectiveness of Local Application of Chlorhexidine Gluconate, Mupirocin Ointment, and Normal Saline for the Prevention of Peritoneal Dialysis-related Infections (COSMO-PD Trial): a multicenter randomized, double-blind, controlled protocol.

BACKGROUND: Current international guidelines recommend the use of a daily topical exit-site antimicrobial to prevent peritoneal dialysis (PD)-related infections. Although nonantibiotic-based therapies are appealing because they may limit antimicrobial resistance, no controlled trials have been conducted to compare topical antimicrobial agents with usual exit-site care for the prevention of PD-related infections among the Thai PD population. We propose a controlled three-arm trial to examine the efficacy and safety of a daily chlorhexidine gluconate-impregnated patch versus mupirocin ointment versus usual exit-site care with normal saline for the prevention of PD-related infections. METHODS/DESIGNS: This study is a randomized, double-blind, multicenter, active-controlled, clinical trial. Adult patients aged 18 years or older who have end-stage kidney disease and are undergoing PD will be enrolled at three PD Centers in Thailand. A total of 354 PD patients will be randomly assigned to either the 2% chlorhexidine gluconate-impregnated patch, mupirocin ointment, or usual exit-site care with normal saline dressing according to a computer-generated random allocation sequence. Participants will be followed until discontinuation of PD or completion of 24 months. The primary study outcomes are time to first PD-related infection (exit-site/tunnel infection or peritonitis) event and the overall difference in PD-related infection rates between study arms. Secondary study outcomes will include (i) the rate of infection-related catheter removal and PD technique failure, (ii) rate of nasal and exit-site Staphylococcus aureus colonization, (iii) healthcare costs, and (iv) skin reactions and adverse events. We plan to conduct a cost-utility analysis alongside the trial from the perspectives of patients and society. A Markov simulation model will be used to estimate the total cost and health outcome in terms of quality-adjusted life years (QALYs) over a 20-year time horizon. An incremental cost-effectiveness ratio in Thai Baht and U.S. dollars per QALYs gained will be illustrated. A series of probabilistic sensitivity analyses will be conducted to assess the robustness of the cost-utility analysis findings. DISCUSSION: The results from this study will provide new clinical and cost-effectiveness evidence to support the best strategy for the prevention of PD-related infections among the Thai PD population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02547103. Registered on September 11, 2015.

Effectiveness of Renin-Angiotensin-Aldosterone System Blockade on Residual Kidney Function and Peritoneal Membrane Function in Peritoneal Dialysis Patients: A Network Meta-Analysis.

We performed a network meta-analysis of randomised controlled trials (RCTs) and non-randomised studies in adult peritoneal dialysis patients to evaluate the effects of specific renin-angiotensin aldosterone systems (RAAS) blockade classes on residual kidney function and peritoneal membrane function. Key outcome parameters included the following: residual glomerular filtration rate (rGFR), urine volume, anuria, dialysate-to-plasma creatinine ratio (D/P Cr), and acceptability of treatment. Indirect treatment effects were compared using random-effects model. Pooled standardised mean differences (SMDs) and odd ratios (ORs) were estimated with 95% confidence intervals (CIs). We identified 10 RCTs (n = 484) and 10 non-randomised studies (n = 3,305). Regarding changes in rGFR, RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) were more efficacious than active control (SMD 0.55 [0.06-1.04] and 0.62 [0.19-1.04], respectively) with the protective effect on rGFR observed only after usage ≥12 months, and no differences among ACEIs and ARBs. Compared with active control, only ACEIs showed a significantly decreased risk of anuria (OR 0.62 [0.41-0.95]). No difference among treatments for urine volume and acceptability of treatment were observed, whereas evidence for D/P Cr is inconclusive. The small number of randomised studies and differences in outcome definitions used may limit the quality of the evidence.

A Clinical Risk Prediction Tool for Peritonitis-Associated Treatment Failure in Peritoneal Dialysis Patients.

A tool to predict peritonitis-associated treatment failure among peritoneal dialysis (PD) patients has not yet been established. We conducted a multicentre, retrospective cohort study among 1,025 PD patients between 2006 and 2016 in Thailand to develop and internally validate such a tool. Treatment failure was defined as either a requirement for catheter removal, a switch to haemodialysis, or peritonitis-associated mortality. Prediction model performances were analysed using discrimination (C-statistics) and calibration (Hosmer-Lemeshow test) tests. Predictors were weighted to calculate a risk score. In total, 435 patients with 855 episodes of peritonitis were identified; 215 (25.2%) episodes resulted in treatment failure. A total risk score of 11.5 was developed including, diabetes, systolic blood pressure <90 mmHg, and dialysate leukocyte count >1,000/mm3 and >100/mm3 on days 3-4 and day 5, respectively. The discrimination (C-statistic = 0.92; 95%CI, 0.89-0.94) and calibration (P > 0.05) indicated an excellent performance. No significant difference was observed in the internal validation cohort. The rate of treatment failure in the different groups was 3.0% (low-risk, <1.5 points), 54.4% (moderate-risk, 1.5-9 points), and 89.5% (high-risk, >9 points). A simplified risk-scoring scheme to predict treatment failure may be useful for clinical decision making regarding PD patients with peritonitis. External validation studies are needed.