Clinical trial NCT02000414: Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Peritoneal Infection
Official title: Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Patients With Peritoneal Dialysis and Peritoneal Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peritoneal Infection
Keywords: intraperitoneal
peritoneal dialysis
daptomycin
pharmacokinetics
peritonitis
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
First posted: 2013-12-04
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: dose-finding study
Primary purpose: TREATMENT

Brief summary: Peritoneal infection is still a frequent complication in peritoneal dialysis patients . In France, It contributes to the technique failure, responsible for about 20% of cases of transfer in hemodialysis. The risk of direct mortality is estimated at 1 to 6% according to studies. Peritoneal infection is involved in the dysfunction of the peritoneal membrane.

Based on the recommendations of the International Society for Peritoneal Dialysis, the intraperitoneal route is preferentially recommended. For many antibiotics, pharmacokinetics (intravenous and intraperitoneal) was studied and protocols for IP administration were validated.

Daptomycin, is a cyclic lipopeptide natural, active only on Gram-positive bacteria. It is presented as an alternative to vancomycin in infections resistant pathogens. The stability of daptomycin in peritoneal dialysis fluids (PDF) has been tested, and antimicrobial activity as well.

Seven patients were treated with daptomycin intraperitoneally successfully. But no study has reported pharmacokinetics of daptomycin via the IP route. We propose a pharmacokinetic study of daptomycin administered intraperitoneally in 12 patients on CAPD and with Gram-positive peritoneal infection.

Detailed description: Methodology:

Prospective, open-label, non-randomized pharmacokinetic study. Daptomycin will be given IP in the CAPD fluid (200mg in 2L Nutrineal) once daily, in a 6 hours-dwell time. The process of dialysis is done four times per day : three during the day (6,6,and 4 h) and one time at night (8h). Duration of treatment depends on bacteria identified (14 or 21 days).

Analyses will be performed on data from all patients meeting the criteria for inclusion and exclusion.

For each patient, plasma, dialysate and urine kinetics will be studied.

For each parameter, mean and standard deviation are calculated.

Number of centers \& patients:

One center, twelve patients.

Sample size justification:

This is an observational pharmacokinetic study of consecutive PD patients presenting to Caen University Hospital with peritoneal infection and who meet inclusion criterias over one year.

Population: CAPD patients with a Gram positive peritoneal infection

Eligibility criteria: Inclusion Criteria:

Patients \> 18 years

* Hospitalized CAPD patients with Gram positive peritoneal infection : ISPD criterias
* Presence of two clinical signs and symptoms : abdominal pain, nausea, vomiting, diarrhea, fever and cloudy dialysate
* Peritoneal dialysate WBC\>100/µL with at least 50% polymorphonuclear neutrophil cells
* Demonstration of bacteria on Gram stain or culture
* on peritoneal dialysis for at least 3 months
* written consent, obtained from either the patient, one of his/her relatives, the trusted person who was designated beforehand or, if not possible, emergency enrollment.
* patient has a life expectancy greater than 6 months

Exclusion Criteria:

* Known allergy to daptomycin
* Peritoneal infection with Gram negative only
* Patient with CPK\>5UNL
* patients already treated with antibiotics, antifungals within 4 weeks prior to the event
* Patient with hepatic impairment
* Patient with arguments for an extra-peritoneal site of infection
* Patient with severe intercurrent illness (eg, hematologic malignancies, patients on chemotherapy)
* Infection by daptomycin-resistant germ
* HMGCoA reductase, fibrates or ciclosporin treatment
* Pregnant or breast-feeding women

Primary outcomes:
measure: Pharmacokinetics
timeFrame: 14 days
Secondary outcomes:
measure: tolerance
timeFrame: 14 days
Other outcomes:
Locations:
city: Caen
country: France
facility: Néphrologie CHU de Caen
Study officials:
affiliation: University Hospital, Caen
name: Thierry Lobbedez, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Caen
name: Maxence FICHEUX, Dr
role: STUDY_DIRECTOR
References: