Clinical trial NCT00748345: Pharmacokinetics of Caspofungin in Burn Patients
Official title: Pharmacokinetics of Caspofungin in Burn Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Thermal Injury
Keywords: Caspofungin,
burn patients,
pharmacokinetics,
optimal dose,
antifungal treatment
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2008-09-08
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Drug pharmacokinetics of antimicrobial agents is significantly altered in the burn patients. Additionally, burn patient population exhibits a wide inter- and intrapatient variation in drug handling. Several investigations carried out in burn patients treated with e.g. fluconazole showed the requirement to increase daily dose in comparison with healthy volunteers. However, no pharmacokinetic data are available of caspofungin in the burn population. The aim of this investigation is to investigate pharmacokinetics of caspofungin in burn patients after a single usual dose (70 mg i.v.), in order to determine the optimal dose in this population.

Detailed description: The aim of this investigation is to investigate pharmacokinetics of caspofungin in burn patients after a single usual dose (70 mg i.v.). Blood samples are drawn just before administration and 0.25, 0.5,1 1.5, 3, 6, 12, 24, 48, 72, 96 and 120 hours after administration. Caspofungin plasma concentrations are measured by liquid-chromatography spectrometry mass tandem.The primary end-points are :

* area under the curve of caspofungin plasma concentrations over 24 hours
* mean peak level and trough concentration (24 hours after dosing)

The secondary end-points are :

* mean total clearance
* mean distribution volume These parameters will be compared to those usually observed in non burn patients. The optimal dose in burn patients is the dose achieving an exposure similar to that in non burn patients.

Eligibility criteria: Inclusion Criteria:

* 18 - 60 years old
* burn surface : 20-60% total body surface area
* delay of injury time : 8-15 days
* lack of fungal infection
* delay of hospitalization : \> 5 days
* written informed consent
* last biological picture in 24 hours before inclusion

Exclusion Criteria:

* survival inferior to 5 days
* surgical intervention planned in the next five days following inclusion
* moderate or severe hepatic impairment according to Child Plug B \> 9
* pregnancy
* allergy to caspofungin or excipients (saccharose, mannitol and frozen acetic acid)
* patient already included in other study
* concomitant administration of CYP450 inducers : rifampicin, efavirenz, phenobarbital, phenytoin, carbamazepine
* withdrawal of consent
* event (during the first 48 hours following administration) susceptible to modify pharmacokinetic parameters
* Investigator decision
* no social security insurance

Primary outcomes:
measure: area under the curve of caspofungin plasma concentrations over 24 hours mean peak level and trough concentration (24 hours after dosing)
timeFrame: 18 months
Secondary outcomes:
measure: mean total clearance
timeFrame: 18 months
measure: mean distribution volume
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Cochin
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Christophe Vinsonneau, MD
role: PRINCIPAL_INVESTIGATOR
References: