Denosumab Treatment in CKD Patients at High Risk of Fracture
Denosumab Treatment in Patients With Chronic Kidney Disease (CKD) at High Risk of Fracture: A Prospective, Randomised Controlled Study
Objective: To verify the efficacy and safety of denosumab in the prevention and treatment of CKD-MBD in CKD patients with high risk of fracture.
Methods: A cohort of CKD patients with high risk of fracture was established and followed up for long periods (≥24 months). Patients with CKD3b-5D stage and fracture risk assessment tool (FRAX) scores at high risk or very high risk of fracture were enrolled. A multicenter, prospective, open-label, randomised controlled, interventional study was conducted. The patients were divided into two groups. The patients in the denosumab group received subcutaneous injection of denosumab 60mg once every 6 months, and the patients in the non-denosumab group received conventional treatment. Bone metabolic markers (serum calcium, phosphorus, vitamin D, parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase 5b, osteocalcin, total N-terminal propeptide of type I collagen, etc.), bone mineral density (dual-energy X-ray, quantitative CT), and vascular calcification score were regularly monitored. All adverse events (all-cause death, cardiovascular death, cardiac events, fracture, hospitalization, emergency department visits, etc.) were recorded during the follow-up period. Bone mineral density and clinical parameters were compared between the two groups.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Dongliang Zhang, Director
- Phone Number: +861058396938
- Email: zdlycy@163.com
Study Locations
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Beijing
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Beijing, Beijing, China, 100035
- Recruiting
- Nephrology Department of Beijing Jishuitan Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ≥18 years old;
- Stage 3b-5D chronic kidney disease;
- The 10-year probability of hip fracture assessed by fracture risk assessment tool (FRAX) was >5%;
- Voluntarily signed informed consent.
Exclusion Criteria:
- Age < 18 or ≥100 years;
- Premenopausal women;
- Denosumab was absolutely contraindicated;
- Had received denosumab or bisphosphonates therapy;
- Tertiary hyperparathyroidism;
- Patients with malignant tumor;
- Patients at risk for osteonecrosis of the jaw;
- Estimated follow-up time ≤12 months.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Denosumab group
Fifty-one patients were randomly assigned to the denosumab group, which received subcutaneous injection of denosumab 60mg once every 6 months.
Serum calcium, phosphorus, alkaline phosphatase, iPTH, tPINP, 25(OH)VitD, DXA and qCT were measured before medication.
Serum calcium, phosphorus and iPTH were examined at day 1, 7 and 14, alkaline phosphatase, tPINP and 25(OH)VitD at day 7 and 14, and electrocardiogram at day 1 and 7 after treatment.
Intravenous calcium supplementation was required if muscle spasms and QT prolongation occurred.
Six months after medication, subcutaneous injections of denosumab 60mg were repeated.
The protocol was repeated every 6 months, totally 24 months.
Bone mineral density, clinical parameters and adverse events were evaluated at 24 months.
|
The patients in the denosumab group received subcutaneous injection of denosumab 60mg once every 6 months for 24 months.
|
|
Active Comparator: Non-denosumab group
The other 51 patients did not use denosumab and used other medications, such as diphosphonates, active vitamin D and/or active vitamin D analogue, calcimimetics, calcitonin, estrogen receptor agonists, etc.
At the same time, calcium and vitamin D were supplemented.
The baseline serum calcium, phosphorus, alkaline phosphatase, iPTH, tPINP, 25(OH)VitD, DXA, and qCT were measured.
The above parameters were rechecked every 6 months, and the medications was recorded, totally 24 months.
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Taken other medications, such as diphosphonates, active vitamin D and/or active vitamin D analogue, calcimimetics, calcitonin, estrogen receptor agonists, etc.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Rate of bone mineral density (BMD) decline at the lumbar spine
Time Frame: 24 months
|
Rate of BMD decline =[(BMD24-BMD Baseline)÷BMD baseline]*100%
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24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Rate of fresh fractures, cardiovascular cerebrovascular adverse events and all-cause mortality
Time Frame: 24 months
|
Fresh fractures were new non-traumatic fractures during follow-up.
Cardiovascular cerebrovascular adverse events were Acute myocardial infarction, heart failure, shock, cardiac arrest, stroke, and lower limb arterial occlusion occurred during follow-up.
All-cause mortality was death from any cause during follow-up.
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24 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- K2022-203-00
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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