Comparing Cefepime Versus Cefazolin Plus Ceftazidime for CAPD-associated Peritonitis

Peritoneal Dialysis Associated Peritonitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02872038
• Other study ID #: MONOCEF
• Status: Completed
• Phase: Phase 4
• First received: July 25, 2016
• Last updated: October 30, 2017
• Start date: August 2015
• Est. completion date: November 30, 2016

Study information

• Verified date: October 2017
• Source: Chulalongkorn University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: November 30, 2016
• Est. primary completion date: November 30, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Peritoneal Dialysis Associated Peritonitis
• Peritonitis

Intervention

Drug:
• Cefepime
Cefepime intraperitoneal continuous dosing
• Cefazolin plus Ceftazidime

Locations

Country	Name	City	State
Thailand	Chulalongkorn University	Bangkok

Sponsors (3)

Lead Sponsor	Collaborator
Chulalongkorn University	Siam Pharmaceutical Co Ltd, The Kidney Foundation of Thailand

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Complete cure rate	Complete resolution without relapse or recurrent within 28 days after completion of antibiotics.	28 days after completion of antibiotics
Other	Relapse peritonitis rate	Recur of peritonitis with the same organism or sterile culture within 28 days after completion antibiotics	28 days after completion antibiotics
Other	Recurrent peritonitis rate	Recur of peritonitis with different organism within 28 days after completion antibiotics	28 days after completion antibiotics
Other	Death rate	Death from any cause	28 days after completion antibiotics
Primary	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	Initial response rate	Resolution of clinical peritonitis and peritoneal dialysis fluid WBC < 100 /µL with PMN < 50% at day 5	day 5 of treatment