Chlorhexidine Gluconate Versus Mupirocin Ointment in the Prevention of Peritoneal Dialysis-Related Infection (COSMO-PD)

Efficacy and Safety of Local Application of Chlorhexidine Gluconate Versus Mupirocin Ointment in the Prevention of Peritoneal Dialysis-Related Infection: A Double-Blind, Stratified Randomized Controlled Trial

This pilot study aims to evaluate effectiveness, safety, and cost-utility of chlorhexidine gluconate (CHG)-soaked cloths compares to mupirocin ointment and exit site usual care (normal saline) with aseptic technique in prevention of PD-related infection. It is a multicenter, double-blind, stratified randomized controlled trial. Participants will be randomized to three arms mupirocin, usual care, or CHG-soaked cloths in a ratio of 1:1:1. They will be followed up 24 months or completion of PD. The primary outcome is PD-related infection (PD-related peritonitis of exit-site and tunnel infection). Secondary outcomes are infection-related catheter removal and technique failure, nasal and exit-site Staphylococcus aureus colonization, health-related quality of life, mental health, medication adherence, safety, adverse events related to treatments such as skin irritation, rash, etc. Costs include providers and patients expenses. The utility is assessed using the EuroQol (EQ), five-dimensional (5D), five-level (5L) version. The results of this study are anticipated nephrologists and health care professional involving to PD in decision-making for a plan to prevent PD-related infection. In addition, the results will lead to clinical guideline development a prevention of PD-related infection.

Study Overview

• Status: Unknown
• Conditions: Peritoneal Dialysis; End Stage Renal Disease
• Intervention / Treatment: Other: Normal saline; Other: Chlorhexidine gluconate-soaked cloths; Other: mupirocin ointment

Detailed Description

Peritoneal dialysis (PD) is one of renal replacement therapy used for end-stage renal disease. Since 2011, there has been increasing numbers of patients under "PD First" policy of the Thai government. The most common PD related complication is PD-related infection categorized PD-related peritonitis, and exit site and tunnel infection. Although possible to treat PD-related infection, the incidence of technical failure and death due to peritonitis are still high in Thailand. PD-related infections mainly caused by Staphylococcus aureus. To prevent PD-related infection, cleaning with aseptic solvents using aseptic technique and prevent infection by prescribing prophylactic antibiotics are recommended. The International Society for Peritoneal Dialysis (ISPD) has recommended position statement of the regular use of mupirocin ointment around the catheter exits point and apply in nasal cavity. However, there is rising concern of long term use of mupirocin for mupirocin resistance of S. aureus. CHG is antiseptic use in clinical practice. It can coat at least 12 hours on skin and has anti-bacterial covered in both grams negative and positive. Several meta-analysis studies showed effectiveness of CHG in the prevention of hospitals infection i.e. reduces catheter-related sepsis, postoperative infection, and microbial resistance. According to PD-related infection, CHG has very little evidence of its effectiveness. This pilot study aims to evaluate effectiveness, safety, and cost-utility of CHG-soaked cloths compares to mupirocin ointment and exit site usual care (normal saline and povidone-iodine) with aseptic technique in prevention of PD-related infections. It is a multicenter, double-blind, stratified randomized controlled trial. Participants will be randomized to three arms mupirocin, usual care, or CHG-soaked cloths. They will be followed up 24 months or completetion of PD. The primary outcome is PD-related infection (PD-related peritonitis or exit-site and tunnel infection). Secondary outcomes are infection-related catheter removal and technique failure, nasal and exit-site Staphylococcus aureus colonization, health-related quality of life, mental health, medication adherence, safety, adverse events related to treatments such as skin irritation, rash, etc. For cost-utility analysis, costs include providers and patients expenses. The Utility is assessed using EQ-5D-5L.

• Study Type: Interventional
• Enrollment (Anticipated): 354
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Surapon Nochaiwong; Phone Number: +6653991507; Email: surapon.nochaiwong@gmail.com
• Study Contact Backup: Name: Chidchanok Ruengorn; Phone Number: +6653991507; Email: mei.ruengorn@gmail.com

Study Locations

• Thailand
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • Maharaj Nakorn Chiang Mai Hospital
    • Contact: Kajohnsak Noppakun, Nephrologist; Phone Number: +6653946452; Email: knoppaku@med.cmu.ac.th
    • Contact: Chayutthaphong Chaisai, Pharmacist; Phone Number: +6653941507; Email: c.chayutthaphong@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with end-stage renal disease who were undergoing peritoneal dialysis; either continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD)

Exclusion Criteria:

1. History of psychological illness or condition that interferes with the ability to understand or comply with the requirements of the study
2. Recent (within 1 month) exit-site or tunnel infection, or peritonitis
3. Known hypersensitivity to, or intolerance of, chlorhexidine gluconate, or mupirocin
4. Current or recent (within 1 month) treatment with antibiotics administered by any route
5. Nasal carriage of mupirocin-resistant Staphylococcus aureus or chlorhexidine-resistant S. aureus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chlorhexidine gluconate; Chlorhexidine gluconate-soaked cloths, clean topical area around catheter exit site with CHG 2% soaked cloths	Other: Chlorhexidine gluconate-soaked cloths
Active Comparator: Normal saline (usual care); Normal saline, clean topical area around catheter exit site	Other: Normal saline
Active Comparator: Mupirocin ointment; Mupirocin ointment 2%, clean topical area around catheter exit site with Mupirocin ointment	Other: mupirocin ointment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of PD-related infections	Peritonitis or exit-site and tunnel infection	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of infection-related catheter removal	Peritonitis or exit-site and tunnel infection-related catheter removal	24 months
Incidence of hospitalization due to PD-related infection		24 months
Incidence of PD technical failure (change of modal of dialysis)	change of modal of dialysis	24 months
Incidence of death due to PD-related infection	Death due to peritonitis or exit-site and tunnel infection	24 months
Rate of Staphylococcus aureus colonization	Incidence of nasal or exit-site S. aureus colonization	24 months
Changes in health-related quality of life	Using the Kidney Disease Quality of Life-36 (KDQOL-36), EuroQoL-5 dimension-5 level (EQ-5D-5L)	24 months
Number of participants with depression	Using the Beck Depression Inventory II (BDI-II)	24 months
Changes in medication adherence	Using (i) directly observed to record the use of investigational medicinal products via return plastic sachets and ointment tubes; (ii) global rating on medication adherence by visual analog scale; and (iii) Medication-taking behavior measure for Thai patients (MTB-Thai questionnaire	24 months
Total healthcare costs	Direct medical costs, direct non-medical costs, and indirect costs	24 months
Incidence of skin reactions		24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profiles	Safety of investigational medicinal products related to potential harm (e.g. participant survival, hospitalization, and emergency visit)	24 months

Collaborators and Investigators

• Sponsor: Chiang Mai University
• Collaborators: Health Systems Research Institute, Thailand
• Investigators: Study Director: Chidchanok Ruengorn, Faculty of Pharmacy CMU

Publications and helpful links

General Publications

• Nochaiwong S, Ruengorn C, Noppakun K, Panyathong S, Dandecha P, Sood MM, Saenjum C, Awiphan R, Sirilun S, Mongkhon P, Chongruksut W, Thavorn K; Thai Renal Outcomes Research (THOR) Investigators. 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. Trials. 2019 Dec 19;20(1):754. doi: 10.1186/s13063-019-3953-8.

Helpful Links

• Faculty of Pharmacy, Chiang Mai University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: September 7, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: July 26, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Peritoneal dialysis; Normal saline; Chlorhexidine gluconate; Peritonitis; Mupirocin ointment
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Dermatologic Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Disinfectants; Mupirocin; Chlorhexidine; Chlorhexidine gluconate
• Other Study ID Numbers: THOR-PD Group

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No