Denosumab Treatment in CKD Patients at High Risk of Fracture

Not Applicable

Recruiting

• Conditions: Fracture; Bone Density, Low; Chronic Kidney Diseases; End Stage Renal Disease
• Interventions: Drug: Non-denosumab; Drug: Denosumab

• Registration Number: NCT05692297
• Lead Sponsor: Capital Medical University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-01
• Study Start: 2023-01-01
• Study First Submitted: 2023-01-11
• Study First Submitted QC: 2023-01-11
• Study First Posted: 2023-01-20
• Last Update Submitted: 2023-01-20
• Last Update Posted: 2023-01-25
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 102

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-denosumab group	Non-denosumab	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.
Denosumab group	Denosumab	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.

Primary Outcome Measures

Name	Time	Method
Rate of bone mineral density (BMD) decline at the lumbar spine	24 months	Rate of BMD decline =\[(BMD24-BMD Baseline)÷BMD baseline\]\*100%

Secondary Outcome Measures

Name	Time	Method
Rate of fresh fractures, cardiovascular cerebrovascular adverse events and all-cause mortality	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.

Trial Locations

Locations (1)

Nephrology Department of Beijing Jishuitan Hospital; 🇨🇳 Beijing, Beijing, China