Osteonecrosis of the Hip and Bisphosphonate Treatment

NCT00781261 | Unknown Phase 2

• 1 other identifier: 570989
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

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 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.

Conditions

Osteonecrosis

Keywords

hip; collapse femoral head; bisphosphonates; osteonecrosis

Outcome Measures

Primary Outcomes (1)

• reducing pain and disability in the hip

  1 years

Secondary Outcomes (1)

• reducing progression to femoral head collapse and the need for surgical intervention

  3 years

Study Arms (2)

Control

PLACEBO COMPARATOR

Subjects in the control group will receive a placebo drug for a 1 year period

Drug: Placebo

Zoledronic Acid

ACTIVE COMPARATOR

Subjects in this intervention group will be given 5mg Zoledronic acid as a single injection

Drug: Zoledronic Acid

Interventions

Zoledronic Acid DRUG

Subjects in the intervention group B will be given 5mg Zoledronic acid as a single injection.

Zoledronic Acid

Placebo DRUG

Subjects in the control group will receive a placebo drug for a similar period

Control

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• years (if use \> 48 weeks),
• year (if used \> 8 weeks but \< 48 weeks)
• months (if used \> 2 weeks but \< 8 weeks)
• 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)

Sponsors & Collaborators

• University of Sydney: lead
• Novartis: collaborator

Study Sites (5)

Royal North Shore Hospital, Department of Rheumatology

Sydney, New South Wales, 2065, Australia

RECRUITING

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

RECRUITING

Royal Brisbane and Womens Hospital

Herston, Queensland, 4029, Australia

RECRUITING

The Queen Elizabeth Hospital

Adelaide, South Australia, 5011, Australia

RECRUITING

Cabrini Hospital

Melbourne, Victoria, 3144, Australia

RECRUITING

MeSH Terms

Conditions

Osteonecrosis

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Philip Sambrook, Prof

  University of Sydney

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monique Macara

CONTACT

+61294631888; monique.macara@sydney.edu.au

Lyn March

CONTACT

lyn.march@sydney.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2008
• First Posted: October 28, 2008
• Study Start: August 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 14, 2013

Record last verified: 2013-01

Locations

AU (5)