Zoledronic acid monohydrate for Postmenopausal osteoporosis

Inclusion criteria

• {"criterion_text":"- Women aged ≥ 18 years"}
• {"criterion_text":"- With post-menopausal osteoporosis AND treated with denosumab for at least 2 years"}
• {"criterion_text":"- With post-menopausal osteoporosis -\tAND reaching decision of denosumab withdrawal because of achieved therapeutic target defined as no fracture during treatment; no new risk factors; no BMD decrease > 0.03 g/cm² at the spine or hip"}
• {"criterion_text":"- With post-menopausal osteoporosis -\tAND with a history of severe fracture OR a femoral or a lumbar T-score ≤ −2.5 prior denosumab initiation."}
• {"criterion_text":"- Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research)."}
• {"criterion_text":"- Person affiliated or beneficiary of the French social security scheme."}

Exclusion criteria

• {"criterion_text":"- Bone disease other than post-menopausal osteoporosis, including metabolic bone disease"}
• {"criterion_text":"- Subjects unable to give an informed consent or to fill the case report form"}
• {"criterion_text":"- Subjects under law protection"}
• {"criterion_text":"- Foreseeable poor compliance with the strategy, alcoholism, toxicomania."}
• {"criterion_text":"- Uncontrolled endocrine diseases"}
• {"criterion_text":"- Liver failure"}
• {"criterion_text":"- Cancer not in remission for at least 5 years"}
• {"criterion_text":"- Patients with non-healed jaw injury"}
• {"criterion_text":"- Ongoing treatment with systemic glucocorticoids"}
• {"criterion_text":"- Daily systemic glucocorticoids ≥ 7.5 mg prednisone-equivalent used for at least 3 months, and stopped less than 3 months prior inclusion."}
• {"criterion_text":"- Use of medication affecting bone metabolism during the last year: bisphosphonates, teriparatide, romosozumab, hormone replacement therapy"}
• {"criterion_text":"- Contra-indication to bisphosphonates according to license recommendation including: o\t Chronic kidney disease with Glomerular filtration rate stage > or = G3b (<35 mL/min) o\tPrior allergy to zoledronic acid or another bisphosphonate o\tHypocalcemia"}

Primary endpoints

• {"endpoint_text":"- the proportion of patients who failed: -\t to maintain lumbar BMD, assessed by dual-energy x-ray absorptiometry (DXA) after 1 year of ZOL. The least significant change in BMD being 0.03 g/cm²; -\tor presenting an additional vertebral fracture during 1st year.","definition_or_measurement_approach":"Lumbar BMD assessed by dual-energy x-ray absorptiometry (DXA); least significant change defined as 0.03 g/cm²; additional vertebral fractures assessed during first year."}

Secondary endpoints

• {"endpoint_text":"- the proportion of patients who failed to maintain hip BMD after 1 year of ZOL (least significant change: 0.03 g/cm²)","definition_or_measurement_approach":"Hip BMD assessed by DXA; least significant change defined as 0.03 g/cm²."}
• {"endpoint_text":"- the changes in hip and lumbar BMD from baseline to 1 year after ZOL, and from year 1 to year 2","definition_or_measurement_approach":"Change in BMD at hip and lumbar spine measured by DXA between baseline, 1 year and 2 years."}
• {"endpoint_text":"- the changes from baseline in bone turnover markers (crosslaps, bone alkalin phosphatase, osteocalcin, amino-terminal propeptide of type 1 procollagen, TRAP5b, dickkopf 1, sclerostin), at year 1 and year 2","definition_or_measurement_approach":"Measurement of listed bone turnover markers (e.g. CTX/crosslaps, bone ALP, osteocalcin, P1NP, TRAP5b, DKK1, sclerostin) at baseline, year 1 and year 2."}
• {"endpoint_text":"- the number of morphometric vertebral fractures (by vertebral fracture assessment – VFA or X-rays), of clinical vertebral fractures and of clinical peripheral fractures, at year 1 and year 2","definition_or_measurement_approach":"Fractures identified by VFA or standard X-rays (morphometric vertebral fractures) and clinical fracture reporting at year 1 and year 2."}
• {"endpoint_text":"- the number of adverse events and serious adverse events at year 1 and year 2","definition_or_measurement_approach":"Recording and counting adverse events and serious adverse events up to year 1 and year 2."}
• {"endpoint_text":"- the proportion of patients requiring a second ZOL infusion across groups.","definition_or_measurement_approach":"Proportion of participants receiving a second zoledronic acid infusion; second infusion decision appears linked to biomarker thresholds (e.g. crosslaps) as per protocol."}

France

Earliest CTIS Part Ii Submission Date

11-10-2024

Latest Decision Or Authorization Date

15-11-2024

Processing Time Days

35

Number Of Sites

18

Number Of Participants

200

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Toulouse

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France