Revision Surgery of Total Hip ArthroplastyPhase 2NCT01358669
Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip Arthroplasty
A Phase 2 study testing Denosumab in people with Revision Surgery of Total Hip Arthroplasty, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Revision Surgery of Total Hip Arthroplasty
- What is being tested?
- Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Dec 2011to 31 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Academic Unit of Bone Metabolism
Sheffield, South Yorkshire, S5 7AU
About this study
Official title: Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip
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.
Read the detailed description
This is a single centre, double blinded, randomized, controlled trial of denosumab compared to placebo in adults undergoing revision surgery of total hip arthroplasty due to prosthesis related osteolysis. A total of 30 subjects will be enrolled into the study. Subjects will be randomized to receive either denosumab or placebo. 15 participants will be assigned to each treatment arm.
- 60mg denosumab by injection as a single dose
- Placebo by injection as a single dose After they have given informed consent, all participants will have a screening visit (Visit 1). Participants who are eligible after completing all screening assessments will be randomly assigned to receive one of the two treatments. All screening procedures will be completed within 14 (±7) days before beginning the medication. Study medication will be given at visit 2, which will occur 8 weeks (56 ±7 days) before the date of the planned revision surgery. Participants will attend for 5 visits in total as shown below. Visit 1, Baseline, 2 weeks (±7 days)before being given the study medication
- Informed consent
- Personal and demographic data
- Medical history
- Physical exam
- Weight and height
- Concomitant medication (other medications being taken at the visit)
- Blood samples for eligibility, and bone turnover markers
- Urine samples for bone turnover markers
- Vital signs including blood pressure (BP), heart rate (HR) and temperature
- Personal and demographic data
- Medical history
- Physical exam
- Weight and height
- Concomitant medication (other medications being taken at the visit)
- Blood samples for eligibility, and bone turnover markers
- Urine samples for bone turnover markers
- Vital signs including blood pressure (BP), heart rate (HR) and temperature Visit 2, Randomization and administration of denosumab or placebo (day 0)
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Changes to concomitant medications
- Record of adverse events
- Oxford and Harris hip scores (by questionnaire)
- Pregnancy test if applicable
- Administration of medication
- Vital signs including BP, HR and temperature
- Conebeam CT scan of the affected hip Visit 3, Week 4 (±7 days)
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Record of adverse events
- Record of concomitant medications
- Oxford and Harris hip scores
- Vital signs including BP,HR and temperature
- Check on injection site Visit 4, Week 8 (±14 days) (Revision Surgery)
- Standard preoperative admission procedures
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Adverse events recorded
- Record of concomitant medications
- Oxford and Harris hip scores
- Bone and tissue biopsy
- Vital signs including BP, heart rate and temperature Visit 5, Week 14 (±7 days) (Safety follow up visit)
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Adverse events recorded
- Record of concomitant medications
- Oxford and Harris hip score
- Vital signs including BP and heart rate
- Pregnancy test if applicable
- Plain Xray of the pelvis and hip
- Being tested
- Denosumab, Placebo
- Keywords
- Denosumab, Total Hip Arthroplasty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called Prolia
60mg denosumab by injection as a single dose
PlaceboOther
Placebo by injection as a single dose
| Study group | Role | What they receive |
|---|---|---|
| Denosumab | Active comparator | In this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant Receives: Drug: Denosumab |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Osteoclast number
Absolute difference between study groups in osteoclast number per millimetre at the osteolysis membranebone interface, measured by cell counting in histological sections between the denosumab and placebo groups, 8 weeks after administration of the IMP
Measured: 8 weeks after administration
Secondary outcomes (3)
Change in serum or urine levels of βCTXI, NTXI/Cr, TRAcP5b, CTXMMP, PINP, OPG, RANKL
Difference between the denosumab and placebo groups in mean absolute change in serum or urine levels of βCTXI, NTXI/Cr, TRAcP5b, CTXMMP, PINP, OPG, RANKL, 8 weeks after administration of the IMP
Measured: 8 weeks after administration of the IMP
Difference between the denosumab and placebo groups in mean eroded, quiescent, and osteoblast surfaces at the membrane bone interface
Difference between the denosumab and placebo groups in mean eroded, quiescent, and osteoblast surfaces at the membrane bone interface measured using image analysis software, 8 weeks after administration of the IMP (Bioquant Image Analysis Corp, Nashville, TN, USA)
Measured: 8 weeks after administration of the IMP
Difference between the denosumab and placebo groups in ratio of viable to apoptotic osteoclast, macrophage fibroblast, and osteoblasts by TUNEL staining and relative number of cells staining positive for apoptosis markers
Difference between the denosumab and placebo groups in ratio of viable to apoptotic osteoclast, macrophage fibroblast, and osteoblasts by TUNEL staining and relative number of cells staining positive for apoptosis markers, including but not limited to, Caspase 8, 9, and 3, and proliferation marker Ki67 8 weeks after administration of the IMP
Measured: 8 weeks after administration of the IMP
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2011 (estimated)
- Study start14 Dec 2011
- Primary completion2 Jan 2019
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Revision Surgery of Total Hip ArthroplastyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, University of Sheffield
- Responsible party
- Sponsor
- Investigators
- J M Wilkinson, PhD, FRCS (Tr&Orth), Principal investigator, Sheffield Teaching Hospitals NHS Foundation Trust/University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01358669
- Sponsor's protocol ID
- STH15714
- Status last verified
- Nov 2019
- First submitted
- 11 May 2011
- Last updated
- 29 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Denosumab on Inflammatory Osteolytic Lesion Activity in Total Hip
- ClinicalTrials.gov ID
- NCT01358669
- Acronym / sponsor ID
- STH15714
- Keywords
- Denosumab, Total Hip Arthroplasty
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Amgen, University of Sheffield
- Study start
- 14 Dec 2011 (actual)
- Primary completion
- 2 Jan 2019 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 24 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single centre, double blinded, randomized, controlled trial of denosumab compared to placebo in adults undergoing revision surgery of total hip arthroplasty due to prosthesis related osteolysis. A total of 30 subjects will be enrolled into the study. Subjects will be randomized to receive either denosumab or placebo. 15 participants will be assigned to each treatment arm.
- 60mg denosumab by injection as a single dose
- Placebo by injection as a single dose After they have given informed consent, all participants will have a screening visit (Visit 1). Participants who are eligible after completing all screening assessments will be randomly assigned to receive one of the two treatments. All screening procedures will be completed within 14 (±7) days before beginning the medication. Study medication will be given at visit 2, which will occur 8 weeks (56 ±7 days) before the date of the planned revision surgery. Participants will attend for 5 visits in total as shown below. Visit 1, Baseline, 2 weeks (±7 days)before being given the study medication
- Informed consent
- Personal and demographic data
- Medical history
- Physical exam
- Weight and height
- Concomitant medication (other medications being taken at the visit)
- Blood samples for eligibility, and bone turnover markers
- Urine samples for bone turnover markers
- Vital signs including blood pressure (BP), heart rate (HR) and temperature
- Personal and demographic data
- Medical history
- Physical exam
- Weight and height
- Concomitant medication (other medications being taken at the visit)
- Blood samples for eligibility, and bone turnover markers
- Urine samples for bone turnover markers
- Vital signs including blood pressure (BP), heart rate (HR) and temperature Visit 2, Randomization and administration of denosumab or placebo (day 0)
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Changes to concomitant medications
- Record of adverse events
- Oxford and Harris hip scores (by questionnaire)
- Pregnancy test if applicable
- Administration of medication
- Vital signs including BP, HR and temperature
- Conebeam CT scan of the affected hip Visit 3, Week 4 (±7 days)
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Record of adverse events
- Record of concomitant medications
- Oxford and Harris hip scores
- Vital signs including BP,HR and temperature
- Check on injection site Visit 4, Week 8 (±14 days) (Revision Surgery)
- Standard preoperative admission procedures
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Adverse events recorded
- Record of concomitant medications
- Oxford and Harris hip scores
- Bone and tissue biopsy
- Vital signs including BP, heart rate and temperature Visit 5, Week 14 (±7 days) (Safety follow up visit)
- Blood sampling for bone turnover markers
- Urine sampling for bone turnover markers
- Changes to medical history
- Adverse events recorded
- Record of concomitant medications
- Oxford and Harris hip score
- Vital signs including BP and heart rate
- Pregnancy test if applicable
- Plain Xray of the pelvis and hip
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Active comparator | Drug: DenosumabIn this study we explore the potential for giving a medication (denosumab) that may prevent the loss of bone around the hip replacement implant |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: Prolia60mg denosumab by injection as a single dose | Drug | Denosumab |
| PlaceboPlacebo by injection as a single dose | Other | Placebo |
Primary outcome
Osteoclast number
Time frame: 8 weeks after administration
Absolute difference between study groups in osteoclast number per millimetre at the osteolysis membranebone interface, measured by cell counting in histological sections between the denosumab and placebo groups, 8 weeks after administration of the IMP
3 secondary outcomes
Change in serum or urine levels of βCTXI, NTXI/Cr, TRAcP5b, CTXMMP, PINP, OPG, RANKL
Time frame: 8 weeks after administration of the IMP
Difference between the denosumab and placebo groups in mean eroded, quiescent, and osteoblast surfaces at the membrane bone interface
Time frame: 8 weeks after administration of the IMP
Difference between the denosumab and placebo groups in ratio of viable to apoptotic osteoclast, macrophage fibroblast, and osteoblasts by TUNEL staining and relative number of cells staining positive for apoptosis markers
Time frame: 8 weeks after administration of the IMP
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2022.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J M Wilkinson, PhD, FRCS (Tr&Orth) principal investigator
Sheffield Teaching Hospitals NHS Foundation Trust/University of Sheffield
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab in people with Revision Surgery of Total Hip Arthroplasty, run by Sheffield Teaching Hospitals NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Osteoclast number (time frame: 8 weeks after administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2022; AzTrials last refreshed its copy on 7 Nov 2026.