Bone and Joint Penetration of Oral Doxycycline in Patients Undergoing Total Hip Arthroplasty for Coxofemoral Osteoarthritis

The primary objective is to quantify the penetration of doxycycline into cancellous bone in patients undergoing total hip arthroplasty for coxofemoral osteoarthritis, providing pharmacokinetic data relevant to the treatment of bone infections. Secondary objectives are to assess doxycycline penetration into cortical bone and into synovial fluid, thereby extending the understanding of drug distribution within musculoskeletal compartments.

The trial enrolled adult patients scheduled for elective total hip arthroplasty due to coxofemoral osteoarthritis, encompassing both male and female participants aged 18 to 80 years. All individuals were required to be eligible for French social insurance, provide signed informed consent, and possess the capacity to comprehend study requirements. The sponsor did not provide information on the total number of participants. No specific lifestyle restrictions such as diet, physical activity, or habits were reported as selection criteria. The study focused on non‑infected patients, and the primary pharmacologic agent under investigation was doxycycline.

The study is a Phase 4, non‑interventional pharmacokinetic investigation evaluating the penetration of doxycycline into bone and joint tissues in patients undergoing elective total hip arthroplasty for coxofemoral osteoarthritis. Eligible participants are adults aged 18–80 years scheduled for hip replacement, who provide written informed consent and meet French social insurance requirements. After a screening visit to confirm inclusion criteria, participants receive a single oral dose of 200 mg doxycycline pre‑operatively; intra‑operative collection of cancellous bone, cortical bone, and synovial fluid samples, together with plasma, provides the primary and secondary concentration ratios. Post‑operative follow‑up visits are conducted to monitor safety and to obtain any additional laboratory assessments, culminating in an end‑of‑study visit after the final sample is collected. Participant involvement extends from the screening appointment through the surgical procedure and the final follow‑up, with a total duration of approximately 30 days per subject. Early termination may occur if consent is withdrawn, if eligibility criteria are no longer met, or if adverse events preclude continued participation. Recruitment is planned to commence on 1 June 2026 and to conclude by 1 June 2027.

The experimental medication consists of doxycycline 100 mg film‑coated tablets (DOXYCYCLINE BIOGARAN) that are splittable; each participant receives a total oral dose of 200 mg, administered according to the study schedule.

DOXYCYCLINE ARROW 100 mg, a film‑coated tablet, is administered orally as a 200 mg dose in accordance with the protocol.

DOXYCYCLINE TEVA 100 mg, a splittable tablet (anhydrous form), is given orally at a total dose of 200 mg per participant as specified by the study schedule.

DOXYCYCLINE SANDOZ 100 mg, a splittable tablet containing doxycycline monohydrate, is administered orally in a single 200 mg dose per the protocol.

GRANUDOXY 100 mg, a film‑coated splittable tablet (anhydrous form), is provided orally at a total dose of 200 mg as directed by the study schedule.

No additional non‑experimental treatments, such as placebo or standard‑of‑care therapy, are administered in this study.

Efficacy assessment will be based on quantitative measurement of doxycycline concentrations in relevant tissues and biological fluids, expressed as tissue‑to‑plasma concentration ratios. The primary efficacy parameter is the cancellous bone concentration/plasmatic concentration ratio, which will be determined by measuring doxycycline levels in cancellous bone specimens and concomitant plasma samples. Secondary efficacy parameters include the cortical bone concentration/plasmatic concentration ratio and the synovial fluid concentration/plasmatic concentration ratio, each calculated from doxycycline concentrations measured in cortical bone and synovial fluid, respectively, alongside plasma concentrations.

Sample collection will occur during the surgical procedure for total hip arthroplasty, with corresponding plasma samples obtained at the same time point. Doxycycline concentrations will be quantified using validated analytical methods, and the resulting ratios will be computed for each participant. These ratios will be analyzed to assess the extent of drug penetration into bone and joint tissues.