Denosumab Treatment in CKD Patients at High Risk of Fracture

Sponsor

Capital Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05692297

Collaborator

(none)

102

Enrollment

Location

Arms

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Fracture Bone Density, Low End Stage Renal Disease	Drug: Denosumab Drug: Non-denosumab	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Denosumab Treatment in Patients With Chronic Kidney Disease (CKD) at High Risk of Fracture: A Prospective, Randomised Controlled Study

Actual Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.