Comparing Cefepime Versus Cefazolin Plus Ceftazidime for CAPD-associated Peritonitis

A Multicenter, Randomized, Controlled Trial Comparing Cefepime Monotherapy Versus Combination of Cefazolin Plus Ceftazidime for Empirical Treatment of CAPD-associated Peritonitis

The purpose of this study is to compare the efficacy of empirical antibiotics of CAPD-associated peritonitis with intraperitoneal, continuous dosing of cefepime monotherapy versus combination of cefazolin and ceftazidime. Patients were randomized to be administered either intraperitoneal cefepime 1 g loading then 250 mg all exchanges (treatment group) or cefazolin and ceftazidime (control group) in the same dose.

Study Overview

• Status: Completed
• Conditions: Peritoneal Dialysis Associated Peritonitis
• Intervention / Treatment: Drug: Cefepime; Drug: Cefazolin plus Ceftazidime

Detailed Description

The International Society of Peritoneal Dialysis (ISPD) guideline suggest to use combination of antibiotics to cover both of gram positive and gram negative bacteria. The usual regimen in Thailand is cefazolin plus ceftazidime. Despite combination therapy, monotherapy is also possible for empirical treatment of CAPD-associated peritonitis since it helps to lowering staff burden and lowering risk of contamination. Cefepime could be an ideal antibiotic for empirical treatment of CAPD-associated peritonitis as it is an extended-spectrum cephalosporin, forth generation, covering most of gram positive and gram negative bacteria. In addition, cefepime is not broken down by many of the beta-lactamases and less beta-lactamases inducer. This study aims to prove the noninferiority of cefepime monotherapy to cefazolin plus ceftazidime for empirical treatment of CAPD-associated peritonitis.

CAPD-associated peritonitis was diagnosed by at least two of the following criteria: abdominal pain or cloudy peritoneal dialysis fluid (PDF); PDF white cell count > 100/μL with > 50% polymorphonuclear(PMN); and positive gram stain or culture. The patients were randomized into two groups by block of four randomization, sealed envelope. Treatment group was treated with intraperitoneal (IP) cefepime 1 g loading following by maintenance dose 250 mg IP all exchanges. Control group was treated with cefazolin 1 g IP loading and ceftazidime 1 g IP loading following by maintenance dose of cefazolin and ceftazidime 250 mg IP all exchanges. If a patient had residual urine ≥ 100 ml/day, dose of antibiotics would be increased by 25%.

On the first day, the initial blood tests for complete blood count, electrolyte, BUN, creatinine, calcium, phosphate and magnesium were obtained. While peritoneal dialysis fluid were collected using two methods of bacterial culture, both of centrifugation of 50 ml peritoneal dialysis fluid at 3,000 g for 15 minutes and bedside 5-10 ml of peritoneal dialysis fluid inoculated into the blood culture bottles. PDF gram stain and bacterial culture were done. The patients were followed on day 3, 5, 10, 14, 21 and 28 days after the completion of antibiotic course. If clinical improved, the antibiotics would be adjusted according to the culture result and sensitivity after day 5. If clinical not improved the antibiotics would be step up and Tenckhoff catheter removal was considered (on any day of treatment). The patients were treated at least 14 days or 21 days depend on the culture result (as the recommendation of ISPD guideline 2010).

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10500
    • Chulalongkorn University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age more than 18 years
• CAPD initiation more than 4 weeks

Exclusion Criteria:

• Exit site or tunnel infection
• Sepsis
• Previous CAPD-associated peritonitis treatment within 4 weeks
• Drug allergy to cephalosporin
• Tenckhoff catheter malfunction
• Hospitalization more than 48 hours
• Fungal or Mycobacterium infection
• Suspected secondary peritonitis
• Concomitant antibiotics.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Cefepime intraperitoneal continuous dosing	Drug: Cefepime; Cefepime intraperitoneal continuous dosing
Active Comparator: Control; Cefazolin plus Ceftazidime intraperitoneal continuous dosing	Drug: Cefazolin plus Ceftazidime; Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary response rate	Resolution of clinical peritonitis and peritoneal dialysis fluid WBC < 100 /μL with PMN < 50% at day 10	day 10 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial response rate	Resolution of clinical peritonitis and peritoneal dialysis fluid WBC < 100 /μL with PMN < 50% at day 5	day 5 of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete cure rate	Complete resolution without relapse or recurrent within 28 days after completion of antibiotics.	28 days after completion of antibiotics
Relapse peritonitis rate	Recur of peritonitis with the same organism or sterile culture within 28 days after completion antibiotics	28 days after completion antibiotics
Recurrent peritonitis rate	Recur of peritonitis with different organism within 28 days after completion antibiotics	28 days after completion antibiotics
Death rate	Death from any cause	28 days after completion antibiotics

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Collaborators: The Kidney Foundation of Thailand; Siam Pharmaceutical Co Ltd

Publications and helpful links

General Publications

• Kitrungphaiboon T, Puapatanakul P, Chuengsaman P, Tiskajornsiri K, Halue G, Siribamrungwong M, Matayart S, Chongthanakorn K, Poonvivatchaikarn U, Boonyakrai C, Somboonsilp W, Katavetin P, Praditpornsilpa K, Eiam-Ong S, Johnson DW, Kanjanabuch T. Intraperitoneal Cefepime Monotherapy Versus Combination Therapy of Cefazolin Plus Ceftazidime for Empirical Treatment of CAPD-Associated Peritonitis: A Multicenter, Open-Label, Noninferiority, Randomized, Controlled Trial. Am J Kidney Dis. 2019 Nov;74(5):601-609. doi: 10.1053/j.ajkd.2019.05.011. Epub 2019 Jul 19.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): November 30, 2016

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (Estimate): August 18, 2016

Study Record Updates

• Last Update Posted (Actual): October 31, 2017
• Last Update Submitted That Met QC Criteria: October 30, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Anti-Infective Agents; Anti-Bacterial Agents; Cefazolin; Ceftazidime; Cefepime
• Other Study ID Numbers: MONOCEF