Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis (ZOLARMAB)
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| ClinicalTrials.gov Identifier: NCT03087851 |
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Recruitment Status :
Completed
First Posted : March 23, 2017
Results First Posted : January 14, 2021
Last Update Posted : January 14, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Osteoporosis | Drug: Zoledronic Acid | Phase 4 |
Background: Denosumab is an antibody against receptor-activator of nuclear factor kappa-B ligand that prevents recruitment and differentiation of osteoclasts. Treatment decreases bone resorption and fracture risk. After discontinuation, however, bone resorption increases and the bone mass gained during 2 years of therapy is lost within 1 year. At present denosumab treatment is considered to be life-long.
Aim: To investigate if infusion of zoledronic acid can prevent increases in bone turnover and bone loss in patients previously treated with denosumab and if there is difference between infusing zoledronic acid at six or nine months after the last injection of denosumab or when bone turnover is increased.
Methods: A randomized open label, interventional study in 60 patients investigating if treatment with zoledronic acid prevents bone loss after denosumab treatment when administrated six or nine months after last injection of deno-sumab or when bone turnover is increased. Forty patients will be allocated to the two intervention groups and 20 patients will be followed without treatment for up to 12 months after the last denosumab treatment. The patients in the observation group and the nine months group will be monitored monthly and if s-carboxy-terminal collagen cross-links (s-CTX) increases above 1.26ug/l (50% above the normal range for postmenopausal women and elderly men) infusion of zoledronic acid will be administered. Furthermore, a DXA scan (lumbar spine and hip sites) will be performed after three months in the observation group. If BMD has decreased more than 5% at any site, infusion of zoledronic acid will be administered. Finally, if a patient in the 9 months group or the in the observation group suffers an osteoporotic clinical vertebral or hip fracture, infusion of zoledronic acid will be administered.
The patients will be monitored with DXA 6, 12 and 24 months after the infusion of zoledronic acid. Zoledronic acid will be re-administered if BMD has decreased more than 5% at the lumbar spine, total hip or femoral neck. If s-CTX in-creases above 1.26 ug/l during the 2nd year a second infusion of zoledronic acid will be administered.
Perspectives: Many patients will reach osteopenic BMD levels on treatment with denosumab, however the treatment effect on bone turnover and BMD has been demonstrated to be reversible and it is therefore important to find out if denosumab treatment can be discontinued and bone mass maintained by other measures. This study will show if the bone mass can be maintained by administrating zoledronic acid and if timing of the first dose of zoledronic acid after last dose of denosumab matters. If bone loss can be prevented by zoledronic acid expenses on otherwise life-long denosumab treatment can be saved and long-term side effects of denosumab (atypical femur fractures and osteone-crosis of the jaw) can be prevented.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 61 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis |
| Actual Study Start Date : | March 13, 2017 |
| Actual Primary Completion Date : | August 1, 2020 |
| Actual Study Completion Date : | August 1, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 6-month group
Zoledronic acid will be administered at study day 0. If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site a second infusion of zoledronic acid will be administered.
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Drug: Zoledronic Acid
Intravenous infusion of 5 mg zoledronic acid
Other Name: Zoledronate |
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Active Comparator: 9-months group
Zoledronic acid will be administered depending on increase in s-CTX (above 1.26 ug/l) or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 3. If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site a second infusion of zoledronic acid will be administered. |
Drug: Zoledronic Acid
Intravenous infusion of 5 mg zoledronic acid
Other Name: Zoledronate |
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Active Comparator: Observation group
Zoledronic acid will be administered depending on increase in s-CTX (above 1.26 ug/l), decrease in BMD (more than 5% at any site), or the occurrence of an osteoporotic clinical vertebral or hip fracture, but no later than at month 6. If s-CTX increases above 1.26 ug/l or BMD decreases more than 5% at any site a second infusion of zoledronic acid will be administered. |
Drug: Zoledronic Acid
Intravenous infusion of 5 mg zoledronic acid
Other Name: Zoledronate |
- BMD Lumbar Spine [ Time Frame: Treatment with ZOL + 6 months after ZOL ]Change in lumbar spine BMD from treatment with zoledronate (ZOL) to 6 months after
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| Ages Eligible for Study: | 50 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Postmenopausal women (postmenopausal for at least two years)
- Men above 50 years
- Treatment for at least two years with denosumab
- Last denosumab injection less than five months ago
Exclusion Criteria:
- Low-energy vertebral fracture at any time
- Low-energy hip fracture within the last 12 months
- BMD T-score < -2,5 (lumbar spine, total hip or femoral neck)
- Alendronate treatment for more than three years prior to denosumab treatment
- Ongoing treatment with glucocorticoids
- Metabolic bone disease
- Hormone replacement therapy
- Cancer
- Estimated glomerular filtration rate (eGFR) < 35 mL/min
- Allergy to zoledronic acid
- Hypocalcaemia
- Contraindications for zoledronic acid according to the SPC
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03087851
| Denmark | |
| Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark | |
| Aarhus, Denmark, 8000 | |
| Study Director: | Bente L Langdahl, MD PhD DMSc | Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark |
Documents provided by Anne Sophie Sølling, Aarhus University Hospital:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Anne Sophie Sølling, MD, PhD student, Aarhus University Hospital |
| ClinicalTrials.gov Identifier: | NCT03087851 |
| Other Study ID Numbers: |
2015-005529-37 |
| First Posted: | March 23, 2017 Key Record Dates |
| Results First Posted: | January 14, 2021 |
| Last Update Posted: | January 14, 2021 |
| Last Verified: | December 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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Denosumab Bone turnover markers Bone mineral density |
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Osteoporosis Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases |
Metabolic Diseases Zoledronic Acid Bone Density Conservation Agents Physiological Effects of Drugs |