Clinical trial NCT06601244: Pharmacokinetic Study in the Biliary Complications During Liver Transplantation
Official title: Pharmacokinetic Study of DALBAVANCINE in the Treatment of Biliary Complications During Liver Transplantation
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Liver Transplantation
Keywords: liver transplantation
Biliary complications
DALBAVANCINE
Pharmacokinetics
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with hepatic or biliary tract infection requiring prolonged antibiotic therapy with DALBAVANCINE.

Patients who have liver transplantation complicated by a bilioma or liver abscess.

Brief summary: Liver transplantation is the last treatment for severe liver diseases such as advanced cirrhosis or fulminant hepatitis. This is a heavy treatment can be associated with numerous complications, particularly biliary ones.

The management of biliary complications is mixed, combining endoscopic treatment with biliary protheses and antibiotics.

A cohort study carried out at the Grenoble Alpes University Hospital showed a high prevalence of Enterococcus Faecium during these biliary complications. This epidemiology complicates the treatment, because it presents a natural resistance to cephalosporins and penicillin (60% of resistance to amoxicillin in Grenoble hospital), the first line treatment for biliary infection.

Antibiotic used to treat this infection can be DALBAVANCIN, which are compatible with outpatient follow-up.

Although the results are interesting in term of efficacy, no study has investigated the biliary diffusion of this antibiotic.

Detailed description: This is a prospective observational descriptive monocentric study. As the biliary and blood samples taken are not part of standard patient management, this is a type 3 study involving human subjects.

In order to ascertain the value of antibiotic therapy with DALBAVANCINE for the treatment of biliary complications, it is important first to study the pharmacokinetics of these antibiotics to confirm their proper distribution at this site.

As concerns the study population, all liver transplant patients with biliary complications are eligible for inclusion. After diagnosis of a biliary complication and inclusion, the patient undergoes biliairy drainage (endoscopic or radiological) with bacteriological examination and antibiotic dosage in bile and blood.

Biliary drainage consists of placing biliary protheses repeatedly every 2 months for a year of follow-up. Endoscopic retrograde cholangiopancreatography allow an access to the biliary duct to change protheses and make bacteriological, mycological and antibiotic sample.

The antibiotic treatment consists of one perfusion of 1500 mg of DALBAVANCINE at J1, J7 and M2 after the biliary complication.

Plasma and biliary assays will be checked at M2 and M4 of treatment. These tests will be carried out at the time of changing biliary stents, which are part of routine care for these patients.

Clinical, biological and morphological trends are monitored for 6 months.

Eligibility criteria: Inclusion Criteria:

* Adult
* Social security coverage
* Liver transplant recipient
* Hospitalized at CHUGA
* Presenting biliary complications following liver transplantation, confirmed morphologically by ultrasound, CT scan, or liver MRI:

  * Biliomas / bilioperitoneum
  * Hepatic abscess as described by the radiologist
* Undergoing biliary endoscopy or radiological drainage following the initiation of antibiotic therapy (between H0-H96 and 6 weeks +/- 2 weeks)
* Having expressed their non-opposition to participate in this study.

Exclusion Criteria:

* Patients under guardianship or deprived of liberty. Persons referred to in Articles L1121-5 to L1121-8 of the Public Health Code.
* Patients not affiliated with social security.
* Contraindication to the use of DALBAVANCIN.

Secondary exclusion criteria:

- Discontinuation of antibiotic therapy before the completion of biliary dosage measurements.

Primary outcomes:
measure: Description of biliary diffusion of dalbavancin
timeFrame: At Month 2
Secondary outcomes:
measure: Description of the proportion of patients showing good clinical progress at Month 2 and Month 6.
timeFrame: at Month 2 and Month 6
measure: Description of the proportion of patients showing good biological progress at Month 2 and Month 6.
timeFrame: at Month 2 and Month 6
measure: Description of the proportion of patients showing good morphological progress at Month 2 and Month 6.
timeFrame: at Month 2 and Month 6
measure: Record the occurrence of serious adverse events to evaluate the tolerance of the antibiotic therapy.
timeFrame: at Month2, Month 4 and Month 6
measure: Description of the antibiotic concentrations in bile relative to the MIC of the causative pathogens at Month 2.
timeFrame: at Month 2
measure: Evaluation of the biliary concentration of DALBAVANCIN in comparison with the plasma concentration.
timeFrame: at Month 2 and Month 4
measure: Evaluation of the effectiveness of DALBAVANCIN antibiotic treatment at Month 2 and Month 6.
timeFrame: at Month2 and Month 6
Other outcomes:
Locations:
city: Grenoble
country: France
facility: University Hospital Of Grenoble
Study officials:
affiliation: CHU Grenoble Alpes
name: Salomé GALLET, MD
role: PRINCIPAL_INVESTIGATOR
References: