ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12609000104257

Ethics application status

Approved

Date submitted

22/10/2008

Date registered

13/02/2009

Date last updated

15/08/2013

Type of registration

Prospectively registered

Titles & IDs

Public title

A randomised controlled trial of bisphosphonate therapy in osteonecrosis of the hip.

Scientific title

A randomised controlled trial to study the effectiveness of potent bisphosphonate (Zoledronic Acid) therapy in patients with early osteonecrosis of the hip.

Secondary ID [1]

BONES Study

Universal Trial Number (UTN)

Trial acronym

BONES

Linked study record

Health condition

Health condition(s) or problem(s) studied:

osteonecrosis of the hip

collapse femoral head

Condition category

Condition code

Musculoskeletal

Other muscular and skeletal disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Participants will be randomised to one of two groups, the intervention (zoledronic acid infusion) and control group (placebo infusion). Participants will have a 66% chance of being in the intervention group and a 33% chance of being in the control group. Subjects in the intervention group will be given 5mg Zoledronic acid (via infusion) annually for 3 doses, this means one dose a year for 3 years. Patients with low serum 25OH vitamin D will be supplemented before zoledronate administration.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Subjects in the control group will receive a placebo injection (5mg saline solution) for a similar period.

Control group

Placebo

Outcomes

Primary outcome [1]

The primary outcome of this project will be the number of patients progressing to stage III or IV on the Association Research Circulation Osseous (ARCO) scale on imaging (Magnetic Resonance Imaging (MRI)) at 12 months and with an X-ray at 36 months, including the number of patients requiring surgical intervention on the affected hip.

Timepoint [1]

Measured at 12 months and 36 months

Secondary outcome [1]

Changes on MRI including: size of lesion and bone oedema, measured at baseline and 12 months.

Timepoint [1]

Measured at baseline and 12 months

Secondary outcome [2]

Disability evaluation, The Harris Hip Score (HHS) evaluated by the Rheumatologist or Orthopaedic surgeon, is a multidimensional observational assessment which contains eight items representing pain, walking function, activities of daily living, and range of motion of the hip joint. Final score ranges from 100 (no disability) to 0 (maximum disability). The HHS is an accepted test as it can detect small changes in hip function

Timepoint [2]

Measured at baseline, 12 months and 36 months

Secondary outcome [3]

Quality of life. Questionnaires will be used to assess quality of life (AQoL and SF36). The AQoL consists of 5 dimensions, each of which has 3 items. The SF-36 is a short-form health survey which yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.

Timepoint [3]

Measured at baseline, 12 months and 36 months

Secondary outcome [4]

Adverse effects. Adverse effects of the treatment zoledronic acid will be obtained through open-ended questions in the questionnaire and confirmed by a checklist. A special focus will include dental side effects. All serious adverse events and pregnancies that arise during the conduct of the trial will be reported by the investigator sponsor to Novartis within 24 hours of awareness, irrespective of causality. Follow-up information related to serious adverse events and pregnancies will also be reported within 24 hours of awareness.

Timepoint [4]

Measured at baseline, 12 months and 36 months

Secondary outcome [5]

Direct health care costs including; visits to a health care providers, prescriptions and over the counter medication, hospitalization and interventions. Data on direct health care costs including; visits to a health care providers, prescriptions and over the counter medication, hospitalization and interventions will be collected using monthly diaries. Participants will be requested to update these diaries and return when participants attend for 12, 24 and 36 monthly follow up. Participants will be required to also include data on indirect costs due to days off work or from usual activities.

Timepoint [5]

3 years

Eligibility

Key inclusion criteria

symptoms of pain and disability in at least one hip joint and/or positive MRI findings stage I or II on the ARCO classification

Minimum age

18 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Previous hip joint surgery on the affected hip and/or severe pain and disability at rest if treating clinician has recommended surgery and/or Radiographic or MRI findings suggestive for stage III and IV on the ARCO classification

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

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. If suitable, participants will be invited to join the study. Prior to treatment, the study research staff will perform a baseline assessment including demographic details, age, sex, duration of symptoms, medical history including prior surgery, trauma and medication use and known risk factors for osteonecrosis. Eligible participants will be allocated their treatment according to a computer-generated table of random numbers created by the study biostatistician to balance for age, sex and 2 stages of MRI severity. Treatments will then be dispensed by participating hospital pharmacies with active and placebo tablets and infusions prepared in identical packaging to maintain blinding.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

computer-generated table of random numbers created by the study biostatistician

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/04/2009

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

120

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Novartis

Address [1]

54 Waterloo Road
North Ryde NSW 2113

Country [1]

Australia

Funding source category [2]

Government body

Name [2]

National Health and Medical Research Council

Address [2]

Level 1
16 Marcus Clarke Street
Canberra ACT 2601

Country [2]

Australia

Primary sponsor type

University

Name

University of Sydney/ Northern Clinical School

Address

Royal North Shore Hospital
Pacific Highway
St Leonards 2065

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Secondary sponsor category [2]

None

Name [2]

Address [2]

Country [2]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Harbour Human Research Ethics Committee (HREC)

Ethics committee address [1]

Research Office, Level 13, Kolling Building, Royal North Shore Hospital, Reserve Road, St Leonards, NSW, 2065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

21/10/2008

Ethics approval number [1]

0806-124M

Summary

Brief 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. 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 surace 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 esthablished 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.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Lyn March

Address

Department of Rheumatology
Clinical Administration 7C
Royal North Shore Hospital
Reserve Road
ST LEONARDS NSW 2065

Country

Australia

Phone

+61 2 9463 1890

Fax

+61 2 9463 1077

lyn.march@sydney.edu.au

Contact person for public queries

Name

Monique Macara

Address

Department of Rheumatology
Clinical Administration 7C
Royal North Shore Hospital
Reserve Road
ST LEONARDS NSW 2065

Country

Australia

Phone

+61 2 9463 1888

Fax

monique.macara@sydney.edu.au

Contact person for scientific queries

Name

Lyn March

Address

Department of Rheumatology
Clinical Administration 7C
Royal North Shore Hospital
Reserve Road
ST LEONARDS NSW 2065

Country

Australia

Phone

+61 2 9463 1890

Fax

lyn.march@sydney.edu.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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Documents added automatically

No additional documents have been identified.

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