Ignite Creation Date:
2025-12-24 @ 5:05 PM
Ignite Modification Date:
2026-02-23 @ 3:01 PM
Study NCT ID:
NCT06767150
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-01-09
First Post:
2025-01-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
StrAtegies for Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal OSTeoporosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015663', 'term': 'Osteoporosis, Postmenopausal'}], 'ancestors': [{'id': 'D010024', 'term': 'Osteoporosis'}, {'id': 'D001851', 'term': 'Bone Diseases, Metabolic'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-03', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2030-03', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-01-06', 'studyFirstSubmitDate': '2025-01-06', 'studyFirstSubmitQcDate': '2025-01-06', 'lastUpdatePostDateStruct': {'date': '2025-01-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-01-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2030-03', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maintain lumbar bone mineral density (BMD) after 1 year of ZOL', 'timeFrame': '1 year after inclusion', 'description': 'The proportion of patients who failed to maintain lumbar BMD after 1 year of ZOL according to the Least Significant Change (LSC) criterion'}], 'secondaryOutcomes': [{'measure': 'Maintain hip bone mineral density (BMD) after 1 year of ZOL', 'timeFrame': '1 year after inclusion', 'description': 'The proportion of patients who failed to maintain hip BMD after 1 year of ZOL according to the Least Significant Change (LSC) criterion'}, {'measure': 'the changes in hip and lumbar BMD from baseline', 'timeFrame': 'Day 0, 1 year after inclusion, 2 year after inclusion', 'description': 'the changes in hip and lumbar BMD from baseline to 1 year, and from year 1 to year 2 after ZOL, according to the Least Significant Change (LSC) criterion'}, {'measure': 'the changes from baseline in bone turnover markers', 'timeFrame': '1 year after inclusion, 2 year after inclusion', 'description': 'Bone turnover markers is a composite measure derived from crosslaps, bone alkaline phosphatase, osteocalcin, amino-terminal propeptide of type 1 procollagen, TRAP5b, dickkopf 1, sclerostin'}, {'measure': 'morphometric vertebral fractures', 'timeFrame': '1 year after inclusion, 2 year after inclusion', 'description': 'the number of morphometric vertebral fractures measured by vertebral fracture assessment (VFA) or X-rays, of clinical vertebral fractures and of clinical peripheral fractures'}, {'measure': 'Patients requiring a second ZOL', 'timeFrame': '1 year after inclusion, 2 year after inclusion', 'description': 'the proportion of patients requiring a second ZOL infusion across groups.'}, {'measure': 'Relation between biomarker values and densitometry evolution', 'timeFrame': '3, 6, 9, 12 months after inclusion', 'description': 'the relation is defined by biomarker values (cross laps) and densitometry evolution measured bu osteodensitometry'}, {'measure': 'Relation between biomarker values and appearance of new vertebral fracture', 'timeFrame': '3, 6, 9, 12 months after inclusion', 'description': 'the relation is defined by biomarker values (cross laps) and appearance of new vertebral fracture measured by VFA or X-rays'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Postmenopausal osteoporosis', 'strategy', 'denosumab', 'zoledronate', 'rebound', 'withdrawal'], 'conditions': ['Postmenopausal Osteoporosis']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "Denosumab (Dmab) is a potent and validated treatment for postmenopausal osteoporosis. However, its withdrawal, especially after reaching therapeutic target, is associated with a rebound phenomenon characterized by: (i) an increase in bone turnover markers levels usually within first 6 months off-treatment, (ii) a decrease in BMD, and (iii) an unexpected increased risk of (multiple) vertebral fractures. Although current experts' recommendations propose a post-Dmab bisphosphonates therapy (such as ZOL) to mitigate rebound phenomenon, the optimal strategy is still matter of debate. Data suggesting a protective effect with bisphosphonates (1 infusion of ZOL or weekly alendronate) are scarce, with discrepancies, and highlight that a substantial proportion of patients experiences rebound-related bone loss despite bisphosphonate therapy. Crosslaps, a bone turnover maker, are available for daily clinical practice and reflect the antiresorptive activity of anti-resorptive drugs such as bisphosphonates. Investigator hypothesize that monitoring crosslaps levels, can help to identify patients requiring more intensive bisphosphonate (additional ZOL infusion) therapy to control the post-Dmab rebound phenomenon.\n\nInvestigator propose to compare 2 strategies for Dmab withdrawal in postmenopausal osteoporosis: a standard treatment control group treated with a single ZOL infusion versus a biomarker-guided ZOL group with an additional ZOL infusion in case of insufficient inhibition of bone resorption according to crosslaps."}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'genderBased': True, 'genderDescription': 'postmenopausal osteoporosis', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Women with post-menopausal osteoporosis\n* 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;\n* And with a history of severe fracture or a femoral or lumbar T-score ≤ -2.5 prior denosumab initiation.\n\nExclusion Criteria:\n\n* Dmab use for bone disease other than post-menopausal osteoporosis.\n* Uncontrolled endocrine diseases. Liver failure.\n* 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.\n* Contra-indication to bisphosphonates according to license recommendation including chronic kidney disease with GFR stage \\> or = G3b. Prior intolerance to zoledronic acid.\n* Subjects unable to give an informed consent or to fill the case report form. Subjects under law protection.\n* Foreseeable poor compliance with the strategy, alcoholism, toxicomania.'}, 'identificationModule': {'nctId': 'NCT06767150', 'acronym': 'SAFEST', 'briefTitle': 'StrAtegies for Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal OSTeoporosis', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Toulouse'}, 'officialTitle': 'StrAtegies for Zoledronic Acid Post-dEnosumab Discontinuation in Postmenopausal OSTeoporosis', 'orgStudyIdInfo': {'id': 'RC31/23/0370'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Intensive biomarkers-guided arm', 'description': 'A second infusion when crosslaps levels reach 300 pg/mL, no later than month-12', 'interventionNames': ['Drug: a second infusion of ZOL when crosslaps levels reach 300 pg/mL']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Standard treatment arm', 'description': 'Potentially a rescue second infusion at month-12, in case unfavourable outcome (incident osteoporotic fractures) or high risk of unfavourable outcome', 'interventionNames': ['Drug: a rescue second infusion at month-12 (standard traitment)']}], 'interventions': [{'name': 'a second infusion of ZOL when crosslaps levels reach 300 pg/mL', 'type': 'DRUG', 'description': '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', 'armGroupLabels': ['Intensive biomarkers-guided arm']}, {'name': 'a rescue second infusion at month-12 (standard traitment)', 'type': 'DRUG', 'description': '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', 'armGroupLabels': ['Standard treatment arm']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Amiens', 'country': 'France', 'contacts': [{'name': 'Vincent GOEB', 'role': 'CONTACT'}], 'facility': 'Amiens Hospital', 'geoPoint': {'lat': 49.9, 'lon': 2.3}}, {'city': 'Bordeaux', 'country': 'France', 'contacts': [{'name': 'Nadia MEHSEN', 'role': 'CONTACT'}], 'facility': 'Bordeaux Hospital', 'geoPoint': {'lat': 44.84124, 'lon': -0.58046}}, {'city': 'Cahors', 'country': 'France', 'contacts': [{'name': 'Slim LASSOUED', 'role': 'CONTACT'}], 'facility': 'Cahors Hospital', 'geoPoint': {'lat': 44.4491, 'lon': 1.43663}}, {'city': 'Dax', 'country': 'France', 'contacts': [{'name': 'Emilie SHIPLEY', 'role': 'CONTACT'}], 'facility': 'Dax Hospital', 'geoPoint': {'lat': 43.71032, 'lon': -1.05366}}, {'city': 'Le Mans', 'country': 'France', 'contacts': [{'name': 'Guillaume DIREZ', 'role': 'CONTACT'}], 'facility': 'Le Mans Hospital', 'geoPoint': {'lat': 48.0021, 'lon': 0.20251}}, {'city': 'Lille', 'country': 'France', 'contacts': [{'name': 'Bernard CORTET', 'role': 'CONTACT'}], 'facility': 'Lille Hospital', 'geoPoint': {'lat': 50.63391, 'lon': 3.05512}}, {'city': 'Limoges', 'country': 'France', 'contacts': [{'name': 'Anna BILLO', 'role': 'CONTACT'}], 'facility': 'Limoges Hospital', 'geoPoint': {'lat': 45.83362, 'lon': 1.24759}}, {'city': 'Marseille', 'country': 'France', 'contacts': [{'name': 'Sophie TRIJAU', 'role': 'CONTACT'}], 'facility': 'Marseille Hsopital', 'geoPoint': {'lat': 43.29695, 'lon': 5.38107}}, {'city': 'Montpellier', 'country': 'France', 'contacts': [{'name': 'Paulina SZAFORS', 'role': 'CONTACT'}], 'facility': 'Montpellier Hospital', 'geoPoint': {'lat': 43.61093, 'lon': 3.87635}}, {'city': 'Nice', 'country': 'France', 'contacts': [{'name': 'Veronique BREUIL', 'role': 'CONTACT'}], 'facility': 'Nice Hospital', 'geoPoint': {'lat': 43.70313, 'lon': 7.26608}}, {'city': 'Orléans', 'country': 'France', 'contacts': [{'name': 'Eric LESPESSAILLES', 'role': 'CONTACT'}], 'facility': 'Orléans Hospital', 'geoPoint': {'lat': 47.90248, 'lon': 1.90407}}, {'city': 'Paris', 'country': 'France', 'contacts': [{'name': 'Karine BRIOT', 'role': 'CONTACT'}], 'facility': 'Cochin Hospital', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Paris', 'country': 'France', 'contacts': [{'name': 'Thomas FUNCK-BRENTANO', 'role': 'CONTACT'}], 'facility': 'Lariboisiere Hospital', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Poitiers', 'country': 'France', 'contacts': [{'name': 'Guillaume LARID', 'role': 'CONTACT'}], 'facility': 'Poitiers Hospital', 'geoPoint': {'lat': 46.58261, 'lon': 0.34348}}, {'city': 'Rennes', 'country': 'France', 'contacts': [{'name': 'François ROBIN', 'role': 'CONTACT'}], 'facility': 'Rennes Hospital', 'geoPoint': {'lat': 48.11109, 'lon': -1.67431}}, {'city': 'Saint-Etienne', 'country': 'France', 'contacts': [{'name': 'Thierry THOMAS', 'role': 'CONTACT'}], 'facility': 'Saint Etienne Hospital', 'geoPoint': {'lat': 45.43389, 'lon': 4.39}}, {'city': 'Toulouse', 'country': 'France', 'contacts': [{'name': 'Yannick DEGBOE', 'role': 'CONTACT'}, {'name': 'Anna GOSSET', 'role': 'CONTACT'}], 'facility': 'Toulouse Hospital', 'geoPoint': {'lat': 43.60426, 'lon': 1.44367}}], 'centralContacts': [{'name': 'Yannick DEGBOE, MD', 'role': 'CONTACT', 'email': 'degboe.y@chu-toulouse.fr', 'phone': '05 61 77 73 75', 'phoneExt': '+33'}, {'name': 'Charline DAGUZAN', 'role': 'CONTACT', 'email': 'daguzan.c@chu-toulouse.fr', 'phone': '05 61 77 84 90', 'phoneExt': '+33'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Toulouse', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}