A study to see if a drug called Denosumab, affecting bone tissue and mineralization of the bone, will improve the outcome of Total Hip replacement surgery.

Phase 1

• Conditions: Patients with titanium press-fit acetabular components with polyethylene liners will be screened for osteolytic lesions. The patients had primary surgery at least 7 years before screening and all operated due to osteoarthritis of the hip. We expect that approximately 30% of screened patients will have an osteolytic lesion. These patients with screening-detected lesions as well as patients with previously known osteolytic lesions will be eligible for inclusion in the study.; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

• Registration Number: EUCTR2013-004940-48-SE
• Lead Sponsor: Danderyds Hospital, Department of Clinical Sciences, Division of Orthopaedics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-10-03
• Last Update Posted: 5 July 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• Age 40-85 years
• Short Portable Mental Status Questionnaire (SPMSQ) also named Pfeiffertest =7 correct responses or alternatively = 3 incorrect responses
• Male and females
• The primary THA performed at least 7 years before inclusion.
• The primary THA performed due to osteoarthritis or congenital dysplasia of the hip.
• Uncemented cup fixation
• Baseline osteolytic lesion of at least 2 cm³ and at most 40 cm³ around an uncemented acetabular component with a polyethylene liner.
• Participant is willing and able to follow study protocol and has provided informed consent prior to any study specific procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

• Women that are pregnant or women planning to become pregnant or planning to breastfeed
• For women of childbearing potential (menopausal state -determined??): Subject refuses to use 1 highly effective method of contraception (contraceptive pill, intra uterine contraceptive device) for the duration of the study and for 5 months after the last dose of study medication.
• For women of childbearing potential: Subject refrain from breastfeeding for the duration of the study and for 5 months after the last dose of study medication.
• For males with a partner of childbearing potential: Subject refuses to use a condom for the duration of the study and for 5 months after the last dose of study medication.For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 5 months after the last dose of study medication.
• Women that are pregnant or breastfeeding or women planning to become pregnant or planning to breastfeed.
• Pain in the operated hip (because the presence of hip pain in combination with an osteolytic lesion is an indication for revision surgery) as defined by a visual analog scale (VAS) score >3
• Previous revision surgery of the hip i.e. exchange of any inplant after the primary surgery
• Inflammatory arthritis
• Previous participation in clinical trials with denosumab or administration of commercial denosumab (Prolia™ or Xgeva™)
• Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
• Treatment with any intravenous bisphosphonate, fluoride (except for dental treatment) or strontium ranelate within 5 years prior to inclusion.
• Treatment with any oral bisphosphonate within 1 year prior to inclusion.
• Treatment with cortisol or cytostatic drugs within 6 months prior to inclusion.
• Administration of any of the following treatments 3 months prior to screening:
Anabolic steroids or testosterone
Glucocorticosteroids (= 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of = 50 mg)
Calcitonin
Calcitriol or vitamin D derivatives [vitamin D contained in supplements or multivitamins is allowed]
Other bone active drugs including anti-convulsives (except benzodiazepines, gabapentin and pregabalin) and heparin
Chronic systemic ketoconazole, ACTH (adrenocorticotrophic hormone), cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.
Androgen deprivation therapy
• Hypocalcaemia.
• Bone metabolic disorders (such as OI, PHPT, Paget)
• History of osteonecrosis of the jaw and/or recent (within prior 6 months) tooth extraction or dental surgery; or planned invasive dental proceedures during the study
• Serum 25-OH D <15 ng/ml
• Significant malabsorption including Celiac Disease, Short Bowel Syndrome, Crohn’s Disease, Previous Gastric Bypass.
• Active cancer and/or malignancy in last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
• History of solid organ or bone marrow transplant.
• Hypersensitivity to any components of study drug.
• Intolerance to calcium supplements.
• Pregnancy and/or currently lactating.
• Significantly impaired renal function as determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault formula of ? 30 mL/min/1.73 m2
• Elevated transaminases = 2.0 x upper limit of normal (ULN); Elevat

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective is to study the efficacy of denosumab in reducing wear-induced osteolysis around uncemented acetabular implants used in THA.;Secondary Objective: The change in volume of the osteolytic lesion over 2 years. <br>Percentage change of the lesion over the study period. <br>Hip-specific outcome scores at inclusion and 1, 2 and 3 years. <br>Percent change in BMD in vertebrae L1-L4 to investigate if there is an overall increase in bone mass in these patients. <br>Correlation between change in bone turnover markers and progression of osteolysis. <br>Changes in Serum Concentrate values for RANKL and Osteoprogesterin, to determine how Serum level correlates with changes in Osteolytic Volume. <br>Occurrence of AE´s.<br>;Primary end point(s): The change in volume of the osteolytic lesion over 3 years (measured with 3D-CT in cm³): <br>Efficacy(3 years) = Volume(3 years) - Volume(baseline). ;Timepoint(s) of evaluation of this end point: Screening, 3 years