Clinical trial NCT03267225: Genetic Determinants of Clindamycin/Rifampin Interaction
Official title: Study on the Genetic Determinants of Clindamycin/Rifampin Interaction
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: VA Drug Interaction
Keywords: drug interaction
genetic polymorphism
Lead sponsor: Groupe Hospitalier Diaconesses Croix Saint-Simon
Sponsor class: OTHER
Collaborators: name: Fondation Ophtalmologique Adolphe de Rothschild
First posted: 2017-08-30
Enrollment: 84
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: patient treated for a bone or joint infection with a clindamycin/rifampin combination therapy, for at least 10 days

Brief summary: Main objective- To study the influence of the polymorphisms of nuclear receptor proteins pregnane X receptor (PXR), Liver X receptor alpha (LXRα), and Cytochrome P450 (CYP450) on the clindamycin clearance during clindamycin/rifampin combination therapy.

Secondary objectives To study the influence of these polymorphisms on clindamycin clearance, before combination therapy with rifampin (clindamycin monotherapy) To study the influence of these polymorphisms on CYP450 activity before combination therapy with rifampin (clindamycin monotherapy) To study the influence of these polymorphisms on the increase of CYP450 activity after clindamycin/rifampin combination therapy To study the difference between the expected and observed clindamycin serum concentrations after dosage adjustment, in patients with clindamycin dosage adjustment after combination therapy with rifampin

Detailed description: Eligible patients will be informed on the study during their hospitalisation in the unit for the treatment of bone and joint infection by the medical doctor. If they agree to participate in the study, the following samples will be performed :

* After at least 24 hours of clindamycin therapy and before combination therapy with rifampin:

  * 1 urine sample (5 mL) for CYP 450 activity phenotyping
  * 1 blood sample (5 mL on ethylenediaminetetraacetic acid (EDTA) tubes) for measuring clindamycin serum concentration and genotyping
* After ten days of clindamycin-rifampin combination therapy:

  * 1 urine sample (5 mL) for CYP 450 activity phenotyping
  * 1 blood sample (5 mL on EDTA tubes) for measuring clindamycin serum concentration and genotyping

Eligibility criteria: Inclusion Criteria:

* bone or joint infection
* aged ≥ 18 years old
* treatment with clindamycin/rifampin combination therapy \> 10 days

Exclusion Criteria:

* prescription of another treatment with potential action on CYP450
* pregnant or breast feeding patient

Primary outcomes:
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance with clindamycin/rifampin combination therapy
timeFrame: 10 days after onset of clindamycin/rifampin combination therapy
Secondary outcomes:
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance before combination therapy with rifampin (clindamycin monotherapy)
timeFrame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity before combination therapy with rifampin
timeFrame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
measure: Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity after clindamycin/rifampin combination therapy
timeFrame: 10 days after onset of clindamycin/rifampin combination therapy
measure: Difference between expected and observed clindamycine serum concentration after dosage adjustment, in patients after combination therapy with clindamycin and rifampin,.
timeFrame: 10 days after onset of clindamycin/rifampin combination therapy
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses Croix Saint Simon
Study officials:
affiliation: GH Diaconesses Croix Saint Simon
name: Valérie Zeller, MD
role: PRINCIPAL_INVESTIGATOR
References: