Pharmacokinetics Study of Intraperitoneal Administration of Daptomycin in Peritoneal Infection (DAPTODP)

Caen University Hospital

Status

Completed

Conditions

Peritoneal Infection

Treatments

Drug: intraperitoneal daptomycin

Study type

Interventional

Funder types

Other

Identifiers

NCT02000414

2012-005699-33

Details and patient eligibility

About

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.

Full 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

Enrollment

8 patients

Sex

All

Ages

18 to 100 years old

Volunteers

No Healthy Volunteers

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