Genetic Determinants of Clindamycin/Rifampin Interaction

VA Drug Interaction Clinical Trial

— CLINDA-RIFAM  

Official title:

Study on the Genetic Determinants of Clindamycin/Rifampin Interaction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03267225
• Other study ID #: D-VZR_2015_3
• Status: Completed
• Start date: January 2016
• Est. completion date: April 15, 2021

Study information

• Verified date: October 2022
• Source: Groupe Hospitalier Diaconesses Croix Saint-Simon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: April 15, 2021
• Est. primary completion date: April 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• VA Drug Interaction

Locations

Country	Name	City	State
France	Groupe Hospitalier Diaconesses Croix Saint Simon	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Dr Valerie ZELLER	Fondation Ophtalmologique Adolphe de Rothschild

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance with clindamycin/rifampin combination therapy	Impact of PXR, LXRa, CYP 450 3A4/A5 polymorphism on clindamycin clearance after combination clindamycin-rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.	10 days after onset of clindamycin/rifampin combination therapy
Secondary	Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance before combination therapy with rifampin (clindamycin monotherapy)	Impact of PXR, LXRa, CYP 450 3A4/A5 polymorphism on clindamycin clearance before rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.	One to four days after onset of clindamycin therapy and before starting rifampin therapy
Secondary	Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity before combination therapy with rifampin	Impact of PXR, LXRa, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity before combination therapy with rifampin will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.	One to four days after onset of clindamycin therapy and before starting rifampin therapy
Secondary	Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity after clindamycin/rifampin combination therapy	Impact of PXR, LXRa, CYP 450 3A4/A5 polymorphism on CYP 450 3A activity after combination with rifampin therapy will be analyzed by studying the association of these polymorphisms and clindamycin serum concentrations.	10 days after onset of clindamycin/rifampin combination therapy
Secondary	Difference between expected and observed clindamycine serum concentration after dosage adjustment, in patients after combination therapy with clindamycin and rifampin,.	The gap between the predicted and observed clindamycin serum concentrations will be quantified by MPE (Mean Prediction Errors) and RMSE (Root Mean Square Prediction Errors). Dosage adjustment will be considered predictive of the concentration if MPE and RMSE are < 20 %.	10 days after onset of clindamycin/rifampin combination therapy