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

• Study Type: Interventional
• Enrollment (Anticipated): 102
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dongliang Zhang, Director; Phone Number: +861058396938; Email: zdlycy@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100035
      • Recruiting
      • Nephrology Department of Beijing Jishuitan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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)

Number of Arms

2

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.	Drug: Denosumab; 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.	Drug: Non-denosumab; Taken other medications, such as diphosphonates, active vitamin D and/or active vitamin D analogue, calcimimetics, calcitonin, estrogen receptor agonists, etc.

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	Rate of BMD decline =[(BMD24-BMD Baseline)÷BMD baseline]*100%	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of fresh fractures, cardiovascular cerebrovascular adverse events and all-cause mortality	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.	24 months

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 20, 2023

Study Record Updates

• Last Update Posted (Estimate): January 24, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Treatment; Fracture; Denosumab; Chronic Kidney Diseases
• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Wounds and Injuries; Renal Insufficiency; Musculoskeletal Diseases; Bone Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Fractures, Bone; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: K2022-203-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No