Denosumab Treatment in CKD Patients at High Risk of Fracture

NCT05692297 | Unknown

• 1 other identifier: K2022-203-00
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Diseases; Fracture; Bone Density, Low; End Stage Renal Disease

Keywords

Denosumab; Chronic Kidney Diseases; Treatment; Fracture

Outcome Measures

Primary Outcomes (1)

• Rate of bone mineral density (BMD) decline at the lumbar spine

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

  24 months

Secondary Outcomes (1)

• Rate of fresh fractures, cardiovascular cerebrovascular adverse events and all-cause mortality

  24 months

Study Arms (2)

Denosumab group

EXPERIMENTAL

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

Non-denosumab group

ACTIVE COMPARATOR

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

Interventions

Denosumab DRUG

The patients in the denosumab group received subcutaneous injection of denosumab 60mg once every 6 months for 24 months.

Denosumab group

Non-denosumab DRUG

Taken other medications, such as diphosphonates, active vitamin D and/or active vitamin D analogue, calcimimetics, calcitonin, estrogen receptor agonists, etc.

Non-denosumab group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Capital Medical University: lead

Study Sites (1)

Nephrology Department of Beijing Jishuitan Hospital

Beijing, Beijing Municipality, 100035, China

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Fractures, Bone; Bone Diseases, Metabolic; Kidney Failure, Chronic

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Wounds and Injuries; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Dongliang Zhang, Director

CONTACT

+861058396938; zdlycy@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Nephrology Department of Beijing Jishuitan Hospital

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: January 20, 2023
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 25, 2023

Record last verified: 2023-01

Locations

CN (1)