OsteonecrosisPhase 2BONESNCT00781261
Osteonecrosis of the Hip and Bisphosphonate Treatment
A Phase 2 study testing Zoledronic Acid in people with Osteonecrosis, run by University of Sydney at 5 sites in Australia.
Trial summary
Osteonecrosis of the hip is an important cause of musculoskeletal disability and finding therapeutic solutions has proven to be challenging. Osteonecrosis means death of bone which can occur from the loss of the blood supply or some other means. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Osteonecrosis
- What is being tested?
- Zoledronic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 5 sitesAustralia
- Study dates
- Aug 2009to Dec 2013
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- aged between 18-90 years,
- symptoms of pain and disability in at least one hip joint, or
- positive MRI findings stage I or II on the ARCO classification
Who cannot join
- previous hip joint surgery on the affected hip
- severe pain and disability at rest if treating clinician has recommended surgery
- radiographic or MRI findings suggestive for stage III and IV on the ARCO classification
- any iv bisphosphonate within the prior 2 years or any prior use of bisphosphonate preparations, except according to the washout schedule:
- 2 years (if use > 48 weeks),
- 1 year (if used > 8 weeks but < 48 weeks)
Show all 19Show fewer
- 6 months (if used > 2 weeks but < 8 weeks)
- 2 months (if used < 2 weeks)
- active primary hyperparathyroidism
- hypothyroidism, not appropriately controlled with long-term thyroxine therapy
- history of iritis or uveitis, except due to trauma, and resolved for > 2 years prior to study
- self-reported history of diabetic nephropathy or retinopathy (if diabetic, Hb A1c > 10%)
- urine dipstick greater than or equal to 2+ protein at screening
- AST or ALT greater than twice the upper limit of normal and/or alkaline phosphatase greater than twice the upper limit of normal
- serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.00 mmol/L (8.0 mg/dL)
- serum 25-hydroxyvitamin D concentrations < 15 ng/L m) baseline renal insufficiency (calculated creatinine clearance less than 40 mL/min and serum creatinine greater than 175 mol/L) at V1
- a history of invasive malignancy of any organ system, treated or untreated, in the past five years; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, ductal carcinoma in-situ (DCIS), and carcinoma in-situ (CIS) of the uterine cervix
- any candidate patient with severe dental problems or current dental infections and/or any candidate patient with recent or impending dental surgery within three months of dosing
- women of childbearing potential not using the contraception method(s) specified in this study (specify), as well as women who are breastfeeding
Trial locations and contacts
5 sites in 1 country.
Lyn March contact
5 sites in 1 country
Australia5 sites, 5 recruiting
- Recruiting
The Queen Elizabeth Hospital
Adelaide, South Australia, 5011
Catherine Hill, A/Prof, +618 82226688, Catherine.Hill@health.sa.gov.au
Sarah Downie-Doyle, +618 8133 4029, Sarah.Downie-Doyle2@health.sa.gov.au
- Recruiting
Princess Alexandra Hospital
Brisbane, Queensland, 4102
Genni Lynch, (07) 3176 6640, Genni_Lynch@health.qld.gov.au
Cameron Cooke, Dr
- Recruiting
Royal Brisbane and Womens Hospital
Herston, Queensland, 4029
A/Prof Emma Duncan, e.duncan@uq.edu.au
Janelle McFarlane, j.mcfarlane@uq.edu.au
- Recruiting
Cabrini Hospital
Melbourne, Victoria, 3144
Rachelle Buchbinder, +613 95081652, rachelle.buchbinder@med.monash.edu.au
Rachelle Buchbinder, Prof
- Recruiting
Royal North Shore Hospital, Department of Rheumatology
Sydney, New South Wales, 2065
Monique Macara, +61294631888, monique.macara@sydney.edu.au
Professor Lyn March, lyn.march@sydney.edu.au
About this study
Official title: A Randomised Controlled Trial of Bisphosphonate Therapy in Osteonecrosis of the Hip
Osteonecrosis of the hip is an important cause of musculoskeletal disability and finding therapeutic solutions has proven to be challenging. Osteonecrosis means death of bone which can occur from the loss of the blood supply or some other means. Although any age group may develop osteonecrosis, most patients are between 20 and 50 years old. The most common risk factor is a history of high steroid treatment for some medical condition. The next most common associated condition is a history of high alcohol use. There are some cases of osteonecrosis that occur in patients that are otherwise completely healthy with no detectable risk factors.
In the earliest stage of the disease, x-rays appear normal and the diagnosis is made using MRI. The advanced stages of osteonecrosis begin when the dead bone starts to fail mechanically through a process of microfractures of the bone. As the disease progresses, the surface begins to collapse until, finally the integrity of the joint is destroyed. A wide range of surgical treatments with variable success rates have been proposed for the treatment of the osteonecrosis to preserve joint integrity, including core decompression, whereby the venous hypertension that ensues is lessened and revascularisation may be induced leading to bone repair. Nonsurgical treatment options are limited and usually result in a poor prognosis. Early stage disease can be treated with protected weight bearing and physiotherapy, however some studies have shown protected weight bearing to be associated with a greater than 85% rate of femoral head collapse. Unfortunately most studies indicate that the risk for disease progression is greater with nonsurgical treatment than with surgical intervention. There are no established pharmaceuticals for the prevention of treatment of osteonecrosis. Evidence is increasing that the nitrogen containing bisphosphonates may be beneficial in the treatment of osteonecrosis. One bisphosphonates (alendronate) has been evaluated in 60 patients diagnosed with osteonecrosis of the hip. Recent clinical studies have shown very promising results. All patients had symptomatic improvement after one year. Although the follow up time ranged from 3 months to 5 years, only 6 patients progressed to the point of needing surgery.
Read the detailed description
Osteonecrosis (ON) of the hip is an important cause of musculoskeletal disability and finding therapeutic solutions has proven challenging. Patients who are affected with ON are often relatively young, usually in the third to sixth decade of life. ON of the hip is an increasingly common cause of musculoskeletal disability. It can cause pain with or without loss of function of the joint and often ends in substantial use of health care resources and disability. ON of the hip usually progresses to severe destruction of the femoral head with resultant degeneration of the hip joint, in most cases requiring joint replacement.
Early diagnosis has been made easier using magnetic resonance imaging (MRI), however no common satisfactory therapy has been developed for the early stage of the disease. Early surgery aimed at preserving the femoral head has been proposed, such as vascularised fibula grafting. However, the results of this invasive technique do not seem to be widely reproducible, and more minor interventions such as core drilling have high failure rates. Evidence is increasing that the nitrogen containing bisphosphonates may be beneficial in the treatment of ON. Data from clinical trials with patients with ON of the hip suggested that the bisphosphonate alendronate would reduce pain and disability and may reduce progression to femoral head collapse that usually would require surgical intervention.
With this study we aim to determine the efficacy of bisphosphonate therapy (zoledronic acid) versus placebo for reducing pain and disability in ON of the femoral head necrosis (palliative endpoint) and to investigate the effect of bisphosphonate therapy versus placebo in reducing progression to femoral head collapse and the need for surgical intervention (therapeutic endpoint).
Methods This will be a 2-armed double-blind randomised trial of a) zoledronic acid 5mg annually for 3 doses b) placebo drug infusions. Participants will be recruited primarily from rheumatologists and orthopaedic surgeons from multiple centres in Australia. We plan to include 4 major centres in capital cities in Australia and each centre would recruit approximately 30 participants. Potential participants who meet the eligibility criteria will be identified by their treating Rheumatologists or Orthopaedic surgeons, followed by a screening assessment conducted by the study research staff. Eligible participants will be randomised prior to the start of treatment. Prior to treatment, the study research staff will perform a baseline assessment over the phone, including demographic details, age, sex, duration of symptoms, medical history including prior surgery, trauma and medication use and known risk factors for ON. Furthermore at baseline, the Rheumatologists or Orthopaedic surgeon will perform a clinical evaluation using a slightly modified Harris Hip Score (HHS). The study research staff will contact the participants every 6 months to monitor the participant's condition and evaluate pain and disability. Additionally the participants will have a clinical evaluation and MRI scan at 12 months.
This novel clinical research protocol will aim to provide further evidence of the protective value of alendronate or zoledronic acid in patients with ON of the hip. It will determine whether bisphosphonates slow the progression of symptoms as well as the progression to total collapse of the hip. Additionally it will seek to answer questions regarding the comparative effectiveness and also cost-effectiveness of the use of bisphosphonates in early disease. The results of this study can lead to change in treatment of early disease ON and delay and possibly prevent surgical intervention.
- Conditions
- Osteonecrosis
- Being tested
- Zoledronic Acid, Placebo
- Keywords
- hip, collapse femoral head, bisphosphonates, osteonecrosis
- Medical subject headings
- Osteonecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic AcidDrug
Subjects in the intervention group B will be given 5mg Zoledronic acid as a single injection.
PlaceboDrug
Subjects in the control group will receive a placebo drug for a similar period
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Subjects in the control group will receive a placebo drug for a 1 year period Receives: Drug: Placebo |
| Zoledronic Acid | Active comparator | Subjects in this intervention group will be given 5mg Zoledronic acid as a single injection Receives: Drug: Zoledronic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
reducing pain and disability in the hip
Measured: 1 years
Secondary outcomes (1)
reducing progression to femoral head collapse and the need for surgical intervention
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2008 (estimated)
- Study startAug 2009
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteonecrosisStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sydney
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Philip Sambrook, Prof, Principal investigator, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00781261
- Sponsor's protocol ID
- 570989
- Acronym
- BONES
- Status last verified
- Jan 2013
- First submitted
- 27 Oct 2008
- Last updated
- 14 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Bisphosphonate Therapy in Osteonecrosis of the Hip
- ClinicalTrials.gov ID
- NCT00781261
- Acronym / sponsor ID
- BONES / 570989
- Conditions
- Osteonecrosis
- Keywords
- hip, collapse femoral head, bisphosphonates, osteonecrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of SydneyUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Aug 2009
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 28 Oct 2008 (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.
Osteonecrosis of the hip is an important cause of musculoskeletal disability and finding therapeutic solutions has proven to be challenging. Osteonecrosis means death of bone which can occur from the loss of the blood supply or some other means. Although any age group may develop osteonecrosis, most patients are between 20 and 50 years old. The most common risk factor is a history of high steroid treatment for some medical condition. The next most common associated condition is a history of high alcohol use. There are some cases of osteonecrosis that occur in patients that are otherwise completely healthy with no detectable risk factors.
In the earliest stage of the disease, x-rays appear normal and the diagnosis is made using MRI. The advanced stages of osteonecrosis begin when the dead bone starts to fail mechanically through a process of microfractures of the bone. As the disease progresses, the surface begins to collapse until, finally the integrity of the joint is destroyed. A wide range of surgical treatments with variable success rates have been proposed for the treatment of the osteonecrosis to preserve joint integrity, including core decompression, whereby the venous hypertension that ensues is lessened and revascularisation may be induced leading to bone repair. Nonsurgical treatment options are limited and usually result in a poor prognosis. Early stage disease can be treated with protected weight bearing and physiotherapy, however some studies have shown protected weight bearing to be associated with a greater than 85% rate of femoral head collapse. Unfortunately most studies indicate that the risk for disease progression is greater with nonsurgical treatment than with surgical intervention. There are no established pharmaceuticals for the prevention of treatment of osteonecrosis. Evidence is increasing that the nitrogen containing bisphosphonates may be beneficial in the treatment of osteonecrosis. One bisphosphonates (alendronate) has been evaluated in 60 patients diagnosed with osteonecrosis of the hip. Recent clinical studies have shown very promising results. All patients had symptomatic improvement after one year. Although the follow up time ranged from 3 months to 5 years, only 6 patients progressed to the point of needing surgery.
Detailed description
Osteonecrosis (ON) of the hip is an important cause of musculoskeletal disability and finding therapeutic solutions has proven challenging. Patients who are affected with ON are often relatively young, usually in the third to sixth decade of life. ON of the hip is an increasingly common cause of musculoskeletal disability. It can cause pain with or without loss of function of the joint and often ends in substantial use of health care resources and disability. ON of the hip usually progresses to severe destruction of the femoral head with resultant degeneration of the hip joint, in most cases requiring joint replacement.
Early diagnosis has been made easier using magnetic resonance imaging (MRI), however no common satisfactory therapy has been developed for the early stage of the disease. Early surgery aimed at preserving the femoral head has been proposed, such as vascularised fibula grafting. However, the results of this invasive technique do not seem to be widely reproducible, and more minor interventions such as core drilling have high failure rates. Evidence is increasing that the nitrogen containing bisphosphonates may be beneficial in the treatment of ON. Data from clinical trials with patients with ON of the hip suggested that the bisphosphonate alendronate would reduce pain and disability and may reduce progression to femoral head collapse that usually would require surgical intervention.
With this study we aim to determine the efficacy of bisphosphonate therapy (zoledronic acid) versus placebo for reducing pain and disability in ON of the femoral head necrosis (palliative endpoint) and to investigate the effect of bisphosphonate therapy versus placebo in reducing progression to femoral head collapse and the need for surgical intervention (therapeutic endpoint).
Methods This will be a 2-armed double-blind randomised trial of a) zoledronic acid 5mg annually for 3 doses b) placebo drug infusions. Participants will be recruited primarily from rheumatologists and orthopaedic surgeons from multiple centres in Australia. We plan to include 4 major centres in capital cities in Australia and each centre would recruit approximately 30 participants. Potential participants who meet the eligibility criteria will be identified by their treating Rheumatologists or Orthopaedic surgeons, followed by a screening assessment conducted by the study research staff. Eligible participants will be randomised prior to the start of treatment. Prior to treatment, the study research staff will perform a baseline assessment over the phone, including demographic details, age, sex, duration of symptoms, medical history including prior surgery, trauma and medication use and known risk factors for ON. Furthermore at baseline, the Rheumatologists or Orthopaedic surgeon will perform a clinical evaluation using a slightly modified Harris Hip Score (HHS). The study research staff will contact the participants every 6 months to monitor the participant's condition and evaluate pain and disability. Additionally the participants will have a clinical evaluation and MRI scan at 12 months.
This novel clinical research protocol will aim to provide further evidence of the protective value of alendronate or zoledronic acid in patients with ON of the hip. It will determine whether bisphosphonates slow the progression of symptoms as well as the progression to total collapse of the hip. Additionally it will seek to answer questions regarding the comparative effectiveness and also cost-effectiveness of the use of bisphosphonates in early disease. The results of this study can lead to change in treatment of early disease ON and delay and possibly prevent surgical intervention.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: PlaceboSubjects in the control group will receive a placebo drug for a 1 year period |
| Zoledronic Acid | Active comparator | Drug: Zoledronic AcidSubjects in this intervention group will be given 5mg Zoledronic acid as a single injection |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- aged between 18-90 years,
- symptoms of pain and disability in at least one hip joint, or
- positive MRI findings stage I or II on the ARCO classification
Key exclusion criteria (19 listed)
- previous hip joint surgery on the affected hip
- severe pain and disability at rest if treating clinician has recommended surgery
- radiographic or MRI findings suggestive for stage III and IV on the ARCO classification
- any iv bisphosphonate within the prior 2 years or any prior use of bisphosphonate preparations, except according to the washout schedule:
- active primary hyperparathyroidism
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 |
|---|---|---|
| Zoledronic AcidSubjects in the intervention group B will be given 5mg Zoledronic acid as a single injection. | Drug | Zoledronic Acid |
| PlaceboSubjects in the control group will receive a placebo drug for a similar period | Drug | Control |
Primary outcome
reducing pain and disability in the hip
Time frame: 1 years
1 secondary outcome
reducing progression to femoral head collapse and the need for surgical intervention
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2013.
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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.
Lyn March contact
Philip Sambrook, Prof principal investigator
University of Sydney
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zoledronic Acid in people with Osteonecrosis, run by University of Sydney at 5 sites in Australia.
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 19 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: status not confirmed, as of the sponsor's last update on 14 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Australia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Monique Macara (+61294631888, monique.macara@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
reducing pain and disability in the hip (time frame: 1 years). 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 14 Jan 2013.