StrAtegies For Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal oSTeoporosis
SAFEST
1 other identifier
interventional
200
1 country
17
Brief Summary
Denosumab (Dmab) is a treatment for postmenopausal osteoporosis. However, its withdrawal is associated with a rebound phenomenon associated with an unexpected increased risk of vertebral fractures. Defining the optimal strategy for Dmab withdrawal is critically needed. Investigator propose an open-label randomized superiority strategy trial to compare the 1-year lumbar densitometric efficacy of biomarkers-driven zoledronate (ZOL) infusion vs standardized ZOL treatment to mitigate rebound phenomenon.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Oct 2025
Longer than P75 for phase_4
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 6, 2025
CompletedFirst Posted
Study publicly available on registry
January 9, 2025
CompletedStudy Start
First participant enrolled
October 2, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2030
December 31, 2025
December 1, 2025
5 years
January 6, 2025
December 23, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maintain lumbar bone mineral density (BMD) after 1 year of ZOL
The proportion of patients who failed to maintain lumbar BMD after 1 year of ZOL according to the Least Significant Change (LSC) criterion
1 year after inclusion
Secondary Outcomes (7)
Maintain hip bone mineral density (BMD) after 1 year of ZOL
1 year after inclusion
the changes in hip and lumbar BMD from baseline
Day 0, 1 year after inclusion, 2 year after inclusion
the changes from baseline in bone turnover markers
1 year after inclusion, 2 year after inclusion
morphometric vertebral fractures
1 year after inclusion, 2 year after inclusion
Patients requiring a second ZOL
1 year after inclusion, 2 year after inclusion
- +2 more secondary outcomes
Study Arms (2)
Intensive biomarkers-guided arm
EXPERIMENTALA second infusion when crosslaps levels reach 300 pg/mL, no later than month-12
Standard treatment arm
ACTIVE COMPARATORPotentially a rescue second infusion at month-12, in case unfavourable outcome (incident osteoporotic fractures) or high risk of unfavourable outcome
Interventions
a first infusion of ZOL 5 mg, 6 months after denosumab withdrawal (= study start), and potentially a rescue second infusion at month-12, in case unfavourable outcome (incident osteoporotic fractures) or high risk of unfavourable outcome
a first infusion of ZOL 5 mg, 6 months after denosumab withdrawal (= study start) and a second infusion when crosslaps levels reach 300 pg/mL, no later than month-12
Eligibility Criteria
You may qualify if:
- Women with post-menopausal osteoporosis
- And treated with denosumab for at least 2 years and 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;
- And with a history of severe fracture or a femoral or lumbar T-score ≤ -2.5 prior denosumab initiation.
You may not qualify if:
- Dmab use for bone disease other than post-menopausal osteoporosis.
- Uncontrolled endocrine diseases. Liver failure.
- Use of medication affecting bone metabolism during the last year, including bisphosphonates, teriparatide, romosozumab, Selective Estrogen Receptor Modulators, breast cancer hormonotherapy, glucocorticoids over 5 mg/day.
- Contra-indication to bisphosphonates according to license recommendation including chronic kidney disease with GFR stage \> or = G3b. Prior intolerance to zoledronic acid.
- Subjects unable to give an informed consent or to fill the case report form. Subjects under law protection.
- Foreseeable poor compliance with the strategy, alcoholism, toxicomania.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
Amiens Hospital
Amiens, France
Bordeaux Hospital
Bordeaux, France
Cahors Hospital
Cahors, France
Dax Hospital
Dax, France
Le Mans Hospital
Le Mans, France
Lille Hospital
Lille, France
Limoges Hospital
Limoges, France
Marseille Hsopital
Marseille, France
Montpellier Hospital
Montpellier, France
Nice Hospital
Nice, France
Orléans Hospital
Orléans, France
Cochin Hospital
Paris, France
Lariboisiere Hospital
Paris, France
Poitiers Hospital
Poitiers, France
Rennes Hospital
Rennes, France
Saint Etienne Hospital
Saint-Etienne, France
Toulouse Hospital
Toulouse, France
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 6, 2025
First Posted
January 9, 2025
Study Start
October 2, 2025
Primary Completion (Estimated)
October 1, 2030
Study Completion (Estimated)
October 1, 2030
Last Updated
December 31, 2025
Record last verified: 2025-12