Genetic Determinants of Clindamycin/Rifampin Interaction (CLINDA-RIFAM)

October 24, 2022 updated by: Dr Valerie ZELLER

Study on the Genetic Determinants of Clindamycin/Rifampin Interaction

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

Study Overview

Status

Completed

Conditions

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

Study Type

Observational

Enrollment (Actual)

84

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75020
        • Groupe Hospitalier Diaconesses Croix Saint Simon

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance with clindamycin/rifampin combination therapy
Time Frame: 10 days after onset of clindamycin/rifampin combination therapy
Impact of PXR, LXRα, 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic polymorphism of PXR, LXRalpha, CYP450 on clindamycin clearance before combination therapy with rifampin (clindamycin monotherapy)
Time Frame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
Impact of PXR, LXRα, 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
Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity before combination therapy with rifampin
Time Frame: One to four days after onset of clindamycin therapy and before starting rifampin therapy
Impact of PXR, LXRα, 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
Genetic polymorphism of PXR, LXRalpha, CYP450 on the increase of CYP 3A4 activity after clindamycin/rifampin combination therapy
Time Frame: 10 days after onset of clindamycin/rifampin combination therapy
Impact of PXR, LXRα, 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
Difference between expected and observed clindamycine serum concentration after dosage adjustment, in patients after combination therapy with clindamycin and rifampin,.
Time Frame: 10 days after onset of clindamycin/rifampin combination therapy
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr Valerie ZELLER

Collaborators

Fondation Ophtalmologique Adolphe de Rothschild

Investigators

  • Principal Investigator: Valérie Zeller, MD, GH Diaconesses Croix Saint Simon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

April 15, 2021

Study Completion (Actual)

April 15, 2021

Study Registration Dates

First Submitted

September 9, 2016

First Submitted That Met QC Criteria

August 28, 2017

First Posted (Actual)

August 30, 2017

Study Record Updates

Last Update Posted (Actual)

October 25, 2022

Last Update Submitted That Met QC Criteria

October 24, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • D-VZR_2015_3

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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