Osteoarticular Infections (OAIs)Phase 3AMPHORENCT07764302
Enhancing Amoxicillin Pharmacokinetics and Pharmacodynamics Parameters With Probenecid in Bone and Joint Infections
A Phase 3 study testing Oral probenecid added to oral amoxicillin for osteoarticular infections in people with Osteoarticular Infections (OAIs), run by Assistance Publique - Hôpitaux de Paris at 8 sites in France.
Trial summary
Osteoarticular infections (OAIs) are common, with Streptococcus spp. and Enterococcus spp. being the second most common causative pathogens after Staphylococcus aureus. High-dose oral amoxicillin is recommended as first-line treatment for susceptible infections caused by Streptococcus spp., Enterococcus faecalis and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoarticular Infections (OAIs)
- What is being tested?
- Oral probenecid added to oral amoxicillin for osteoarticular infections
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 8 sitesFrance
- Study dates
- Dec 2026to Sep 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Age ≥ 18 years old
- Effective contraception throughout the study period for women of childbearing potential.
- Ongoing oral amoxicillin monotherapy for the treatment of a documented osteoarticular infection, including: osteoarticular infection without implanted material (arthritis, osteitis, osteomyelitis), osteoarticular infection involving implanted material (osteoarticular prosthesis, osteosynthesis hardware, external fixator, or arthrodesis material excluding spinal instrumentation), or spondylodiscitis with or without implanted material, defined by the following criteria:
- Microbiological documentation of one or more pathogens for which amoxicillin is the recommended antibiotic treatment (Enterococcus spp. susceptible to ampicillin, Streptococcus spp., Cutibacterium spp., and other anaerobic bacteria susceptible to amoxicillin), obtained from blood cultures, disco-vertebral biopsy, bone biopsy, joint aspiration, and/or intraoperative samples.
- Treatment with oral amoxicillin monotherapy for the management of this osteoarticular infection, with the diagnosis established based on the following criteria:
- Clinical signs, with one or more of the following: fever, hypothermia, chills, pain, spinal pain, arthritis, inflammatory or dehiscent scar over osteoarticular hardware, fistula, purulent drainage, and/or
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- Suggestive radiological findings (X-ray, CT scan, or MRI): bone lysis, periosteal reaction, sequestrum, soft tissue collection, joint effusion, radiolucent line around osteoarticular hardware suggestive of loosening. In cases of spondylodiscitis: T2 hyperintensity of the disc, T1 hypointensity of adjacent vertebral endplates on MRI, posterior facet joint arthritis, and/or
- Final diagnosis of osteoarticular infection established by the treating medical or multidisciplinary surgical team based on a combination of clinical, microbiological, radiological, or other relevant findings.
- Patients with a history of one or more previous osteoarticular infections are eligible.
- Oral amoxicillin treatment permitted based on clinical and biological improvement.
- Planned hospitalization duration ≥4 days after inclusion.
- Patient informed and having provided written informed consent to participate.
Who cannot join
- Pregnancy or breastfeeding.
- Severe allergy to β-lactams or documented allergic contraindication to penicillins confirmed by allergy testing.
- Contraindication to probenecid, including: hypersensitivity to probenecid, an ongoing acute gout attack, nephrolithiasis, secondary hyperuricemia due to chemotherapy, radiotherapy, or myeloproliferative syndrome because of the increased risk of uric acid nephropathy, and primary hyperuricemia due to uric acid overproduction.
- Ongoing treatment, which cannot be discontinued, with a medication known to interact with probenecid: methotrexate, diprophylline, cholestyramine, phenobarbital, and zidovudine. If treatment discontinuation is possible, the washout period will be left to the investigator's discretion.
- Renal impairment defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² according to the CKD-EPI equation, based on the most recent value available during hospitalization before inclusion.
- Augmented renal clearance defined by an eGFR >130 mL/min/1.73 m² according to the CKD-EPI equation, based on the most recent value available during hospitalization before inclusion.
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- Body weight <40 kg or >110 kg.
- Severe hepatic impairment defined by prothrombin time (PT) <50%, based on the most recent value available during hospitalization before inclusion.
- Patients under legal guardianship, curatorship, judicial protection, or deprived of liberty.
- Patients with cognitive impairment or who, in the investigator's opinion, are unable to understand the study, participate in all study visits considering the treatments and procedures required by the protocol, and/or provide informed consent.
- Patients not affiliated with a social security system or another health insurance scheme, including patients covered by State medical aid (AME).
- Concomitant participation in another clinical trial involving a medicinal product for human use, a clinical investigation of a medical device, or any interventional research involving human participants.
- Participation in non-interventional research is permitted
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
France8 sites
Hôpital André Mignot, Centre Hospitalier de Versailles
Chesnay, 78150
Audrey Therby, Dr, atherby@ght78sud.fr
Hôpital Beaujon AP-HP
Clichy, 92110
Agnès Lefort, Dr, agnes.lefort@aphp.fr
Hôpital Henri-Mondor, AP-HP
Créteil, 94010
Bérénice Souhail, Dr, +33 1 49 81 24 55, berenice.souhail@aphp.fr
Hôpital Cochin Port Royal, AP-HP
Paris, 75 014
Etienne Canoui, Pr, etienne.canoui@aphp.fr
Hôpital Lariboisière-Fernand Widal, AP-HP
Paris, 75010
Anne-Lise Munier, Dr, anne-lise.munier@aphp.fr
Hôpital Saint-Antoine - AP-HP
Paris, 75012
Laure Surgers, Dr, laure.surgers@aphp.fr
Hôpital Ambroise-Paré, AP-HP
Paris, 92100
Aurélien Dinh, Dr, aurelien.dinh@aphp.fr
Hôpital Bretonneau, CHU Tours
Tours, 37000
Adrien Lemaignen, Dr, adrien.lemaignen@univ-tours.fr
About this study
Official title: Impact du probénécide Sur Les paramètres pharmacocinétiques et Pharmacodynamiques de l'Amoxicilline Chez Des Patients traités Par Voie Orale Pour Une Infection ostéo-articulaire : étude Quasi-expérimentale Multicentrique Preuve de Concept
Osteoarticular infections (OAIs) are common, with Streptococcus spp. and Enterococcus spp. being the second most common causative pathogens after Staphylococcus aureus. High-dose oral amoxicillin is recommended as first-line treatment for susceptible infections caused by Streptococcus spp., Enterococcus faecalis and anaerobic bacteria. However, treatment failure remains frequent despite appropriate therapy, with reported rates ranging from 25% to 48%.
The efficacy of β-lactam antibiotics is closely related to PK/PD target attainment, particularly the time during which free drug concentrations remain above the minimum inhibitory concentration (fT > MIC). For severe infections such as OAIs, maintaining antibiotic concentrations above the MIC throughout the dosing interval is considered the optimal PK/PD target. Because amoxicillin penetration into bone is limited (bone-to-plasma concentration ratio 0.1-0.3), a trough plasma concentration (Cmin) ≥10 × MIC has been proposed to ensure adequate exposure at the site of infection. Achieving this target is particularly challenging for E. faecalis because of its higher MICs and the saturable oral absorption of amoxicillin at doses ≥2 g. Accordingly, the French Infectious Diseases Society (SPILF) recommends PK/PD-guided dose optimization and therapeutic drug monitoring when oral amoxicillin doses exceed 9 g/day.
Read more
Probenecid inhibits the renal tubular secretion of β-lactams through inhibition of OAT1 and OAT3 transporters, thereby increasing plasma amoxicillin concentrations and prolonging its elimination half-life. This pharmacokinetic interaction has been well documented and may improve PK/PD target attainment without increasing the amoxicillin dose. Current national recommendations advocate high-dose amoxicillin but propose heterogeneous dosing regimens, resulting in substantial variability in prescribing practices. The AMPHORE study aims to generate clinical PK/PD data to establish standardized dosing strategies for oral amoxicillin, with or without adjunctive probenecid.
Hypothesis : In patients with osteoarticular infections treated with oral amoxicillin, the addition of probenecid may improve amoxicillin PK/PD target attainment by increasing trough plasma amoxicillin concentrations.
Objective : To evaluate the effect of adding oral probenecid on the trough plasma amoxicillin concentration in patients receiving oral amoxicillin monotherapy for osteoarticular infection.
Method : Prospective, multicentre, quasi-experimental before-and-after study conducted in eight French hospitals. Fifty-seven patients with microbiologically confirmed osteoarticular infections caused by amoxicillin-susceptible pathogens (Enterococcus spp., Streptococcus spp., Cutibacterium spp. or other amoxicillin-susceptible anaerobic bacteria) receiving oral amoxicillin monotherapy will be included. Following baseline pharmacokinetic sampling, patients will receive oral probenecid (500 mg every 8 hours), with repeat pharmacokinetic assessment.
- Conditions
- Osteoarticular Infections (OAIs)
- Being tested
- Oral probenecid added to oral amoxicillin for osteoarticular infections
- Keywords
- Amoxicillin, Probenecid, Osteoarticular infections, Pharmacokinetics/pharmacodynamics (PK/PD)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral probenecid added to oral amoxicillin for osteoarticular infectionsDrug
Adjunctive oral probenecid (500 mg every 8 hours ± 1 hour) added to ongoing oral amoxicillin in adult patients treated for microbiologically documented osteoarticular infections. Probenecid is administered for pharmacokinetic assessment to evaluate its effect on amoxicillin exposure and PK/PD target attainment. Amoxicillin dosing (2 or 3 g every 8 hours ± 1 hour) remains unchanged before and after probenecid administration.
Probenecid will be administered for 24-72 hours for pharmacokinetic assessment. It may subsequently be continued until the end of antibiotic treatment if the amoxicillin trough concentration is below 10 × MIC without probenecid but reaches the target with probenecid, in accordance with the protocol.
| Study group | Role | What they receive |
|---|---|---|
| Amoxicillin-probenecid combination therapy | Experimental | Addition of probenecid to oral amoxicillin therapy. Receives: Drug: Oral probenecid added to oral amoxicillin for osteoarticular infections |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achievement of the amoxicillin PK/PD target (Cmin ≥ 10 × MIC)
The proportion of patients achieving a trough plasma amoxicillin concentration ≥ 10 × the MIC of the causative bacterium (corresponding to 100% of the time spent at concentrations ≥ 10 × MIC in plasma between two amoxicillin doses), with or without probenecid.
Measured: At baseline before probenecid initiation and after 24-72 hours of probenecid treatment.
Secondary outcomes (16)
Clinical and biological treatment success at end of treatment and 6-month follow-up
Quantification of the number of patients achieving clinical and biological success at the end of antibiotic therapy and 6 months after treatment completion.
Measured: At the end of antibiotic treatment and 6 months ± 7 days after treatment completion.
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Quantification of Cmin of amoxicillin without and with probenecid.
Measured: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Cmax of amoxicillin without and with probenecid.
Measured: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
AUC0-8h of amoxicillin without and with probenecid.
Measured: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
t1/2 of amoxicillin without and with probenecid.
Measured: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Renal clearance of amoxicillin without and with probenecid.
Measured: 24-72 hours after probenecid initiation
Establishment a population-based pharmacokinetic/pharmacodynamic (PK/PD) model adapted to patient characteristics incorporating covariates of interest for oral amoxicillin in osteoarticular infections, whether or not associated with probenecid
Population PK/PD analysis: development and validation of a nonlinear mixed-effects model incorporating relevant covariates and Bayesian estimation of individual parameters.
Measured: Through study completion, an average of 2 years
Simulation of dosage regimens to calculate the probabilities of achieving targets based on MICs, and propose an oral amoxicillin dosage regimen-with or without probenecid-for the treatment of osteoarticular infections specific to each pathogen.
Monte Carlo simulations to determine the probability of target attainment according to MIC values, dosing regimen, and the presence or absence of probenecid.
Measured: Through study completion, an average of 2 years
Assessment of the saturability of amoxicillin absorption at doses of 2 g or 3 g per administration.
Comparison of Cmax and AUC0-8h of oral amoxicillin administered at doses of 2 or 3 g.
Measured: Through study completion, an average of 2 years
Analysis of adherence of oral amoxicillin monotherapy versus the combination of oral amoxicillin and probenecid.
Assessment of adherence
Measured: Through study completion, an average of 2 years
Analysis of clinical and biological tolerability of oral amoxicillin monotherapy versus the combination of oral amoxicillin and probenecid.
Description of adverse events
Measured: Through study completion, an average of 2 years
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Quantification of probenecid Cmin.
Measured: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Quantification of probenecid Cmax.
Measured: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Quantification of probenecid AUC0-8h.
Measured: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Quantification of probenecid half-life (t1/2).
Measured: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Quantification of probenecid renal clearance.
Measured: 24-72 hours after probenecid initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2026
- Study startDec 2026 (estimated)
- Primary completionDec 2028 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarticular Infections (OAIs)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A multicenter, non-randomized, comparative, quasi-experimental before-and-after study conducted in adult patients treated with oral amoxicillin monotherapy for an osteoarticular infection.
- Masking
- None (open label)
- Enrolment
- 57 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Souhail Bérénice, Principal investigator, AP-HP. Hôpitaux Universitaires Henri Mondor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07764302
- Sponsor's protocol ID
- APHP251229
- Other IDs
- 2026-525404-95-00
- Acronym
- AMPHORE
- Status last verified
- Aug 2026
- First submitted
- 31 Jul 2026
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Datas are own by assistance publique - hopitaux de paris, please contact sponsor for further information.
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact du probénécide Sur Les paramètres pharmacocinétiques et Pharmacodynamiques de l'Amoxicilline Chez Des Patients traités Par Voie Orale Pour Une Infection ostéo-articulaire : étude Quasi-expérimentale Multicentrique Preuve de Concept
- ClinicalTrials.gov ID
- NCT07764302
- Acronym / sponsor ID
- AMPHORE / APHP251229
- Conditions
- Osteoarticular Infections (OAIs)
- Keywords
- Amoxicillin, Probenecid, Osteoarticular infections, Pharmacokinetics/pharmacodynamics (PK/PD)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 57 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Dec 2026 (estimated)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 13 Aug 2026 (actual)
- 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.
Osteoarticular infections (OAIs) are common, with Streptococcus spp. and Enterococcus spp. being the second most common causative pathogens after Staphylococcus aureus. High-dose oral amoxicillin is recommended as first-line treatment for susceptible infections caused by Streptococcus spp., Enterococcus faecalis and anaerobic bacteria. However, treatment failure remains frequent despite appropriate therapy, with reported rates ranging from 25% to 48%.
The efficacy of β-lactam antibiotics is closely related to PK/PD target attainment, particularly the time during which free drug concentrations remain above the minimum inhibitory concentration (fT > MIC). For severe infections such as OAIs, maintaining antibiotic concentrations above the MIC throughout the dosing interval is considered the optimal PK/PD target. Because amoxicillin penetration into bone is limited (bone-to-plasma concentration ratio 0.1-0.3), a trough plasma concentration (Cmin) ≥10 × MIC has been proposed to ensure adequate exposure at the site of infection. Achieving this target is particularly challenging for E. faecalis because of its higher MICs and the saturable oral absorption of amoxicillin at doses ≥2 g. Accordingly, the French Infectious Diseases Society (SPILF) recommends PK/PD-guided dose optimization and therapeutic drug monitoring when oral amoxicillin doses exceed 9 g/day.
Probenecid inhibits the renal tubular secretion of β-lactams through inhibition of OAT1 and OAT3 transporters, thereby increasing plasma amoxicillin concentrations and prolonging its elimination half-life. This pharmacokinetic interaction has been well documented and may improve PK/PD target attainment without increasing the amoxicillin dose. Current national recommendations advocate high-dose amoxicillin but propose heterogeneous dosing regimens, resulting in substantial variability in prescribing practices. The AMPHORE study aims to generate clinical PK/PD data to establish standardized dosing strategies for oral amoxicillin, with or without adjunctive probenecid.
Hypothesis : In patients with osteoarticular infections treated with oral amoxicillin, the addition of probenecid may improve amoxicillin PK/PD target attainment by increasing trough plasma amoxicillin concentrations.
Objective : To evaluate the effect of adding oral probenecid on the trough plasma amoxicillin concentration in patients receiving oral amoxicillin monotherapy for osteoarticular infection.
Method : Prospective, multicentre, quasi-experimental before-and-after study conducted in eight French hospitals. Fifty-seven patients with microbiologically confirmed osteoarticular infections caused by amoxicillin-susceptible pathogens (Enterococcus spp., Streptococcus spp., Cutibacterium spp. or other amoxicillin-susceptible anaerobic bacteria) receiving oral amoxicillin monotherapy will be included. Following baseline pharmacokinetic sampling, patients will receive oral probenecid (500 mg every 8 hours), with repeat pharmacokinetic assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A multicenter, non-randomized, comparative, quasi-experimental before-and-after study conducted in adult patients treated with oral amoxicillin monotherapy for an osteoarticular infection.
| Arm | Type | Receives |
|---|---|---|
| Amoxicillin-probenecid combination therapy | Experimental | Drug: Oral probenecid added to oral amoxicillin for osteoarticular infectionsAddition of probenecid to oral amoxicillin therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 18 years old
- Effective contraception throughout the study period for women of childbearing potential.
- Ongoing oral amoxicillin monotherapy for the treatment of a documented osteoarticular infection, including: osteoarticular infection without implanted material (arthritis, osteitis, osteomyelitis), osteoarticular infection involving implanted material (osteoarticular prosthesis, osteosynthesis hardware, external fixator, or arthrodesis material excluding spinal instrumentation), or spondylodiscitis with or without implanted material, defined by the following criteria:
- Clinical signs, with one or more of the following: fever, hypothermia, chills, pain, spinal pain, arthritis, inflammatory or dehiscent scar over osteoarticular hardware, fistula, purulent drainage, and/or
- Suggestive radiological findings (X-ray, CT scan, or MRI): bone lysis, periosteal reaction, sequestrum, soft tissue collection, joint effusion, radiolucent line around osteoarticular hardware suggestive of loosening. In cases of spondylodiscitis: T2 hyperintensity of the disc, T1 hypointensity of adjacent vertebral endplates on MRI, posterior facet joint arthritis, and/or
Key exclusion criteria (13 listed)
- Pregnancy or breastfeeding.
- Severe allergy to β-lactams or documented allergic contraindication to penicillins confirmed by allergy testing.
- Contraindication to probenecid, including: hypersensitivity to probenecid, an ongoing acute gout attack, nephrolithiasis, secondary hyperuricemia due to chemotherapy, radiotherapy, or myeloproliferative syndrome because of the increased risk of uric acid nephropathy, and primary hyperuricemia due to uric acid overproduction.
- Ongoing treatment, which cannot be discontinued, with a medication known to interact with probenecid: methotrexate, diprophylline, cholestyramine, phenobarbital, and zidovudine. If treatment discontinuation is possible, the washout period will be left to the investigator's discretion.
- Renal impairment defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² according to the CKD-EPI equation, based on the most recent value available during hospitalization before inclusion.
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 |
|---|---|---|
| Oral probenecid added to oral amoxicillin for osteoarticular infectionsAdjunctive oral probenecid (500 mg every 8 hours ± 1 hour) added to ongoing oral amoxicillin in adult patients treated for microbiologically documented osteoarticular infections. Probenecid is administered for pharmacokinetic assessment to evaluate its effect on amoxicillin exposure and PK/PD target attainment. Amoxicillin dosing (2 or 3 g every 8 hours ± 1 hour) remains unchanged before and after probenecid administration. Probenecid will be administered for 24-72 hours for pharmacokinetic assessment. It may subsequently be continued until the end of antibiotic treatment if the amoxicillin trough concentration is below 10 × MIC without probenecid but reaches the target with probenecid, in accordance with the protocol. | Drug | Amoxicillin-probenecid combination therapy |
Primary outcome
Achievement of the amoxicillin PK/PD target (Cmin ≥ 10 × MIC)
Time frame: At baseline before probenecid initiation and after 24-72 hours of probenecid treatment.
The proportion of patients achieving a trough plasma amoxicillin concentration ≥ 10 × the MIC of the causative bacterium (corresponding to 100% of the time spent at concentrations ≥ 10 × MIC in plasma between two amoxicillin doses), with or without probenecid.
16 secondary outcomes
Clinical and biological treatment success at end of treatment and 6-month follow-up
Time frame: At the end of antibiotic treatment and 6 months ± 7 days after treatment completion.
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Time frame: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Time frame: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Time frame: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Time frame: 24-72 hours after probenecid initiation
Comparison the complete pharmacokinetic parameters of amoxicillin in normorenal adults treated for osteoarticular infection with amoxicillin without and with probenecid.
Time frame: 24-72 hours after probenecid initiation
Establishment a population-based pharmacokinetic/pharmacodynamic (PK/PD) model adapted to patient characteristics incorporating covariates of interest for oral amoxicillin in osteoarticular infections, whether or not associated with probenecid
Time frame: Through study completion, an average of 2 years
Simulation of dosage regimens to calculate the probabilities of achieving targets based on MICs, and propose an oral amoxicillin dosage regimen-with or without probenecid-for the treatment of osteoarticular infections specific to each pathogen.
Time frame: Through study completion, an average of 2 years
Assessment of the saturability of amoxicillin absorption at doses of 2 g or 3 g per administration.
Time frame: Through study completion, an average of 2 years
Analysis of adherence of oral amoxicillin monotherapy versus the combination of oral amoxicillin and probenecid.
Time frame: Through study completion, an average of 2 years
Analysis of clinical and biological tolerability of oral amoxicillin monotherapy versus the combination of oral amoxicillin and probenecid.
Time frame: Through study completion, an average of 2 years
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Time frame: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Time frame: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Time frame: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Time frame: 24-72 hours after probenecid initiation
Description of the complete pharmacokinetic parameters of oral probenecid (500 mg every 8 hours ± 1 hour) in adults with normal renal function treated for Osteoarticular Infections with amoxicillin monotherapy.
Time frame: 24-72 hours after probenecid initiation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Individual participant dataSharing planned: No. Datas are own by assistance publique - hopitaux de paris, please contact sponsor for further information.
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.
Souhail Bérénice principal investigator
AP-HP. Hôpitaux Universitaires Henri Mondor
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oral probenecid added to oral amoxicillin for osteoarticular infections in people with Osteoarticular Infections (OAIs), run by Assistance Publique - Hôpitaux de Paris at 8 sites 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 12 inclusion and 13 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: opening soon, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Souhail Bérénice, Dr (+33 1 49 81 24 55, berenice.souhail@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Achievement of the amoxicillin PK/PD target (Cmin ≥ 10 × MIC) (time frame: At baseline before probenecid initiation and after 24-72 hours of probenecid treatment.). 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 13 Aug 2026.