Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip Arthroplasty

• Status: Unknown status
• Trial end date: 2020-07-31
• Target enrollment: 0
• Participant gender: All

Summary

Although hip replacement surgery is a successful way of dealing with the pain and immobility caused by hip arthritis, 10% of the hip replacements carried out in the UK fail within 10 years. The main reason for this is the development periprosthetic osteolysis, that is, loss of bone around the site of the hip replacement. The osteolysis is thought to be due to the small particles of debris worn from the surfaces of the hip implant. These particles cause a reaction in the blood cells around the joint which in turn affects bone cells and leads to a loss of bone around the implant. The joint implant will then eventually become loose and unstable, a condition known as aseptic loosening. At present the only way to treat aseptic loosening is to have another operation to secure the hip joint, known as revision surgery. Revision surgery is not always successful and exposes the patient to the risk of major surgery.

In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant. We will recruit patients who have been listed for revision surgery. One group of patients will be given a single dose of denosumab; another group will be given a placebo (dummy drug). At the time of the revision surgery a small sample of the bone from around the hip replacement will be taken and examined under the microscope. Comparisons will be made between the patients having the denosumab and those having placebo to find out whether the denosumab is having a beneficial effect on the bone surfaces. If successful, this study will lead to further studies to develop the use of denosumab to prevent aseptic loosening.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Collaborators: Amgen; University of Sheffield
• Treatments: Denosumab

Criteria

Inclusion Criteria:

• Participants must be men or women over 30 years of age undergoing revision THA surgery for periprosthetic osteolysis / aseptic loosening affecting the pelvis and / or femur.

• Participants must also be willing and able to give fully informed consent.

• Participants must have osteolysis / aseptic loosening affecting fully cementless, hybrid, or fully cemented THA prosthesis

Exclusion Criteria:

• Known prosthesis infection

• Pregnancy / Breast feeding

• Oral bisphosphonate therapy (current use, previous use within the last 12 months, previous 3 or more years cumulative use)

• Administration of intravenous bisphosphonate, fluoride or strontium within the last 5 years

• Participation in ongoing or previous denosumab clinical trials

• Administration of any of the following treatments within the last 12 months

• TH or PTH derivatives, eg, teriparatide

• anabolic steroids or testosterone

• glucocorticosteroids (> 5 mg prednisone equivalent per day for more than 10 days)

• systemic hormone replacement therapy

• selective estrogen receptor modulators (SERMs), eg, raloxifene tibolone, calcitonin or calcitriol

• Any subject in whom denosumab is contraindicated according to the local SmPC of denosumab (SC 60 mg every 6 months in UK)

• Current hypocalcemia (albumin adjusted serum calcium below 2.13 mmol/L)

• History of rheumatoid arthritis

• History of Paget's disease

• Malignancy (except basal cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years

• Renal insufficiency assessed by eGFR <30

• Known sensitivity to mammalian cell derived drug products

• Any organic or psychiatric disorder, or laboratory abnormality which, in the opinion of the Investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results

• Any disorder that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures

• Evidence of alcohol or substance abuse within the last 12 months that the Investigator believes would interfere with understanding or completing the study

• Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).