Arthritis, InfectiousCLIRIFANCT02629770
Clindamycin-rifampin Drug Interaction in the Treatment of Bone and Joint Infections
An observational study of Arthritis, Infectious and Bone Diseases, Infectious, run by Groupe Hospitalier Diaconesses Croix Saint-Simon at 1 site in France.
Trial summary
Treatment of bone and joint infections remains difficult and variable according to centres and countries. Clindamycin given intravenously and followed by an oral route is recommended for the treatment of staphylococcal, streptococcal and anaerobes bone and joint infections by the French Society for Infectious… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Infectious, Bone Diseases, Infectious
- What is being tested?
- usual antibiotic treatment
- How many people
- 49 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2015to Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients hospitalized for medical-surgical management of OAIs in the Department of Trauma and Bone Surgery
Who may be able to join
- age ≥18 years
- surgical management of OAI
- Postoperative IV antibiotic therapy for 10±2 days
- Chronic bone and/or joint infection (evolving for >4 weeks) with bacteriologically documented staphylococci, streptococci or susceptible anaerobes in skin flora susceptible to clindamycin and rifampin
- Continuation of IV administration possible for a maximum of 25 days
- Patient consent to participate in the study
- Patients entitled enrolled to a French National Health Insurance
Who cannot join
- Allergy or intolerance to the family of antibiotics used, i.e. lincosamides (clindamycin, lincomycin) and rifamycins (rifampin), or to one of their constituents
- Taking active products able to induce CYP3A4/3A5: alcohol (chronic intake), anti-seizure drugs (carbamazepine, phenobarbital, phenytoin), anti-infectious agents (rifabutin, efavirenz, nevirapine, griseofulvin), anti-fungals (ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, miconazole), calcium channel blockers (diltiazem, verapamil), macrolides (erythromycin, clarithromycin, josamycin, telithromycin)
- Being treated with one of the following: cyclosporine and/or tacrolimus (immunosuppressants) ; midazolam (psychotropic agents)
- Human immunodeficiency virus-positive patient being treated with protease inhibitors (ritonavir, amprenavir, atazanavir, indinavir, nelfinavir, lopinavir, saquinavir) or delavirdine
- Cirrhosis, hepatocellular insufficiency
- Creatinine clearance < 30 mL/min (according to the cockcroft and gault formula)
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- Severe sepsis (systolic blood pressure (SBP) <90 mm Hg; O2 saturation <90%, encephalopathy, oligo-anuria, creatininemia >176 mmol/L, platelets <100,000/mm3, INR >1.5, Glasgow coma score <13) or septic shock (persistent hypotension despite volumetric filling) at arrival in the unit
- Porphyria
- Congenital galactosemia, glucose and galactose malabsorption syndrome, lactase deficit because of the presence of lactose in the dalacin® capsules
- Intolerance of fructose, glucose and galactose malabsorption syndrome, sucrase-isomaltase deficit because of the presence of saccharose in the rifadin® capsules
- Major cognitive disorders, according to the DSM IV-TR (Diagnostic and Statistical Manual of Mental Disorders) definition (36)
- Weight >100 kg or <50 kg
- Woman of childbearing age using estrogen-progestin contraception and not wanting to switch to an effective mechanical-type contraceptive method
- Pregnancy or breast-feeding
- Patient under guardianship
Trial locations and contacts
1 site in 1 country.
France1 site
GH Diaconesses Croix Saint Simon
Paris, Île-de-France Region, 75012
About this study
Official title: Clindamycin-Rifampin Interactions: Effect of Rifampin's Enzyme-induction (Cytochrome P450 3A4/3A5) on Plasma Clindamycin Concentrations, With Clindamycin Given Intravenously and Orally to Treat Bone-and-joint Infections
Treatment of bone and joint infections remains difficult and variable according to centres and countries. Clindamycin given intravenously and followed by an oral route is recommended for the treatment of staphylococcal, streptococcal and anaerobes bone and joint infections by the French Society for Infectious Diseases. For staphylococcal bone and implant infections, rifampin is a major drug, as it remains active in bacterial biofilm and on quiescent staphylococci. For that reasons, clindamycin-rifampin combination therapy is frequently used in these infections.Clindamycin is metabolized by the P450 3A4 cytochrome, an enzyme strongly inducible by rifampin. A retrospective study published in 2010 on 70 patients treated for bone and joint infections showed that clindamycin serum concentrations were significantly lower when clindamycin was combined with rifampin (5.3 mg/liter vs 8.9 mg/liter; p<0.02). This drug interaction could even be stronger with the oral route, because of hepatic first-past effect, ending up with very low clindamycin serum concentration, a risk of selecting resistant microorganisms and treatment failure. This latter point is an important issue, because clindamycin has an excellent oral bioavailability and is frequently used in oral regimens. In the above study, a wide variability of clindamycin serum concentration was observed in the group of patients treated with combination therapy (1-12mg/l) suggesting interindividual variability. Rifampin induction of CYP 450 3A4/A5 depends on different receptor (PXR, RXR, LXRalpha) submitted to genetic polymorphism. Hypothesis: Plasma clearance of clindamycin (CLclin) combined with rifampicin (CLclinrif) is higher when clindamycin is administered by the oral route (CLclinrif OR) compared with IV administration (CLclinrif IV).
- Conditions
- Arthritis, Infectious, Bone Diseases, Infectious
- Being tested
- usual antibiotic treatment
- Medical subject headings
- Arthritis, Infectious, Bone Diseases, Infectious
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
usual antibiotic treatmentDrug
pharmacological studies in patients treated with usual antibiotics, for different types of joint and bone infections
What is being measured
The primary outcome is the main question the study is designed to answer.
mean clearances of clindamycin
The principal evaluation criterion is the mean clearances of clindamycin with and without administration of rifampin (intravenous or oral administration)
Measured: 3 weeks
mean clearances of clindamycin
The principal evaluation criterion is the mean clearances of clindamycin with and without administration of rifampin (intravenous or oral administration)
Measured: 5 weeks
Secondary outcomes (2)
plasma concentrations of IV- or PO-administered clindamycin, combined or not with rifampin.
Measured: 3 weeks
plasma concentrations of IV- or PO-administered clindamycin, combined or not
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arthritis, InfectiousStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Hospitalier Diaconesses Croix Saint-Simon
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation Ophtalmologique Adolphe de Rothschild
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02629770
- Sponsor's protocol ID
- VZR_2014-3
- Acronym
- CLIRIFA
- Status last verified
- Feb 2021
- First submitted
- 10 Dec 2015
- Last updated
- 11 Feb 2021
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clindamycin-Rifampin Interactions: Effect of Rifampin's Enzyme-induction (Cytochrome P450 3A4/3A5) on Plasma Clindamycin Concentrations, With Clindamycin Given Intravenously and Orally to Treat Bone-and-joint Infections
- ClinicalTrials.gov ID
- NCT02629770
- Acronym / sponsor ID
- CLIRIFA / VZR_2014-3
- Conditions
- Arthritis, Infectious, Bone Diseases, Infectious
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Groupe Hospitalier Diaconesses Croix Saint-SimonUniversity, hospital or other
- Collaborators
- Fondation Ophtalmologique Adolphe de Rothschild
- Study start
- Dec 2015 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 14 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment of bone and joint infections remains difficult and variable according to centres and countries. Clindamycin given intravenously and followed by an oral route is recommended for the treatment of staphylococcal, streptococcal and anaerobes bone and joint infections by the French Society for Infectious Diseases. For staphylococcal bone and implant infections, rifampin is a major drug, as it remains active in bacterial biofilm and on quiescent staphylococci. For that reasons, clindamycin-rifampin combination therapy is frequently used in these infections.Clindamycin is metabolized by the P450 3A4 cytochrome, an enzyme strongly inducible by rifampin. A retrospective study published in 2010 on 70 patients treated for bone and joint infections showed that clindamycin serum concentrations were significantly lower when clindamycin was combined with rifampin (5.3 mg/liter vs 8.9 mg/liter; p<0.02). This drug interaction could even be stronger with the oral route, because of hepatic first-past effect, ending up with very low clindamycin serum concentration, a risk of selecting resistant microorganisms and treatment failure. This latter point is an important issue, because clindamycin has an excellent oral bioavailability and is frequently used in oral regimens. In the above study, a wide variability of clindamycin serum concentration was observed in the group of patients treated with combination therapy (1-12mg/l) suggesting interindividual variability. Rifampin induction of CYP 450 3A4/A5 depends on different receptor (PXR, RXR, LXRalpha) submitted to genetic polymorphism. Hypothesis: Plasma clearance of clindamycin (CLclin) combined with rifampicin (CLclinrif) is higher when clindamycin is administered by the oral route (CLclinrif OR) compared with IV administration (CLclinrif IV).
Study design
- Observational model
- Ecologic or community
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients hospitalized for medical-surgical management of OAIs in the Department of Trauma and Bone Surgery
Key inclusion criteria (7 listed)
- age ≥18 years
- surgical management of OAI
- Postoperative IV antibiotic therapy for 10±2 days
- Chronic bone and/or joint infection (evolving for >4 weeks) with bacteriologically documented staphylococci, streptococci or susceptible anaerobes in skin flora susceptible to clindamycin and rifampin
- Continuation of IV administration possible for a maximum of 25 days
Key exclusion criteria (15 listed)
- Allergy or intolerance to the family of antibiotics used, i.e. lincosamides (clindamycin, lincomycin) and rifamycins (rifampin), or to one of their constituents
- Taking active products able to induce CYP3A4/3A5: alcohol (chronic intake), anti-seizure drugs (carbamazepine, phenobarbital, phenytoin), anti-infectious agents (rifabutin, efavirenz, nevirapine, griseofulvin), anti-fungals (ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, miconazole), calcium channel blockers (diltiazem, verapamil), macrolides (erythromycin, clarithromycin, josamycin, telithromycin)
- Being treated with one of the following: cyclosporine and/or tacrolimus (immunosuppressants) ; midazolam (psychotropic agents)
- Human immunodeficiency virus-positive patient being treated with protease inhibitors (ritonavir, amprenavir, atazanavir, indinavir, nelfinavir, lopinavir, saquinavir) or delavirdine
- Cirrhosis, hepatocellular insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| usual antibiotic treatmentpharmacological studies in patients treated with usual antibiotics, for different types of joint and bone infections | Drug | – |
Primary outcome
mean clearances of clindamycin
Time frame: 3 weeks
The principal evaluation criterion is the mean clearances of clindamycin with and without administration of rifampin (intravenous or oral administration)
mean clearances of clindamycin
Time frame: 5 weeks
The principal evaluation criterion is the mean clearances of clindamycin with and without administration of rifampin (intravenous or oral administration)
2 secondary outcomes
plasma concentrations of IV- or PO-administered clindamycin, combined or not with rifampin.
Time frame: 3 weeks
plasma concentrations of IV- or PO-administered clindamycin, combined or not
Time frame: 5 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Arthritis, Infectious and Bone Diseases, Infectious, run by Groupe Hospitalier Diaconesses Croix Saint-Simon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mean clearances of clindamycin (time frame: 3 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2021.