Efficacy of Zoledronic Acid in Enhancement of Early Stability of Cementless Primary Hip Prosthesis

This study has been completed.
Sponsor:
Collaborators:
Academy of Finland
Novartis
Stryker Nordic
Information provided by:
Turku University Hospital
ClinicalTrials.gov Identifier:
NCT01218035
First received: October 7, 2010
Last updated: June 15, 2011
Last verified: June 2011
  Purpose

This is a randomized, double-blind and placebo-controlled study to evaluate the efficacy of zoledronic acid on the biologic incorporation of cementless hip prosthesis in postmenopausal female patients.The study population consists of postmenopausal female patients scheduled for total hip replacement because of degenerative hip osteoarthritis. The patients will receive either a single dose of 5 mg zoledronic acid or placebo intravenously after surgery before hospital discharge. The patients will be followed-up for 1 year. Zoledronic acid therapy has been shown to promote bone ingrowth into porous implants in pre-clinical models. The investigators hypothesis is that zoledronic acid, given as a single intravenous infusion after hip replacement surgery, enhances bone ingrowth into porous surface of cementless hip prostheses. As a primary outcome, the therapy is expected to reduce periprosthetic bone loss measured by DXA. Enhancement of bone ingrowth is expected to increase primary stability of the hip prosthesis and this effect can be detected with high-precision three-dimensional RSA imaging modality and in a faster functional recovery of the patients.


Condition Intervention Phase
Hip Osteoarthritis
Drug: zoledronic acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Zoledronic Acid in Enhancement of Early Stability of Cementless Primary Hip Prosthesis

Resource links provided by NLM:


Further study details as provided by Turku University Hospital:

Primary Outcome Measures:
  • The primary objective of this study is to test whether a single infusion of zoledronic acid reduces periprosthetic bone loss measured by DXA. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • RSA outcome, functional recovery and metabolic treatment response [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    • to demonstrate that the treatment can enhance biologic incorporation of cementless hip prostheses as shown by reduced prosthetic migration measured by RSA (radiostereometry)
    • to demonstrate that enhanced incorporation of the hip prostheses following the therapy lead to faster functional recovery and better subjective outcome of the procedure.
    • to demonstrate that the treatment suppresses biochemical markers of bone resorption.


Enrollment: 49
Study Start Date: May 2007
Study Completion Date: June 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: zoledronic acid
    The patients in the active-treatment group will receive a single 5 mg dose of zoledronic acid intravenously just prior to release from the hospital (about 5th day post-surgery) as an adjunct therapy. The control group will receive a placebo (saline) infusion. All infusions will be given 100 ml in volume and infused over a period of 15 minutes with a pre- and post-infusion flush with normal saline.
Detailed Description:

All the patients enrolled in the study will receive the standard of care with respect to surgical prosthetic replacement of the diseased hip. The patients will receive a custom-modified (RSA marked) hydroxyapatite-coated prosthesis with ceramic-on-ceramic bearing surfaces (SYMAX-TRIDENT, Stryker). The prosthesis modification provided by the manufacturer has a CE mark. The patients in the active-treatment group will receive a single 5 mg dose of zoledronic acid intravenously just prior to release from the hospital (about 5th day post-surgery) as an adjunct therapy. The control group will receive a placebo (saline) infusion. The active and placebo infusion vials will be provided by Norvartis Pharmaceutical. After surgery, before the administration of zoledronic acid or placebo, each patient will be re-screened for the level of serum calcium. In the case of postoperative hypocalcemia, the infusion will be postponed for a minimum of 3-4 weeks and the infusion will be given after the repeated measurements of serum calcium. All patients will receive calcium and D-vitamin supplementation throughout the study period. Efficacy will be assessed on the basis of clinical, radiographic (RSA, DXA, Spiral CT, conventional radiography) and laboratory criteria. The clinical benefit of zoledronic acid therapy is defined in terms of faster functional recovery, which will be analyzed in two ways: (1) the functional outcome (muscle strength, gait analysis and pedometry) will be repeatedly evaluated before and after surgery, and (2) the subjective outcome of the procedure as well as the general health assessment will be determined at each follow-up visits using standardized outcome measures. The primary objective of this study is to test whether a single infusion of zoledronic acid reduces periprosthetic bone loss measured by DXA at 12 months. Statistical significance of differences in periprosthetic bone mineral density between active-treatment and placebo groups will be analyzed using repeated analysis of variance.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Degenerative hip osteoarthritis as the indication for hip replacement
  • Postmenopausal female patient
  • Age of at least 20 years
  • Signed Informed Consent

Exclusion Criteria:

  • Evidence of secondary osteoporosis
  • Clinical or laboratory evidence of hepatic or renal disease
  • Disorders of parathyroid function, or D-vitamin metabolism
  • History of malignancy, radiotherapy, or chemotherapy for malignancy (except for basal cell carcinoma of the skin) within the past 5 years
  • No metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing
  • Administration for more than 7 days of drugs, which may interfere with bone metabolism:

    • cumulative dose of 500 mg of prednisone or equivalent within the last 6 months
    • calcitonin within the last 6 months
    • bisphosphonates for 30 days or more within the last 12 months
    • bone therapeutic doses of fluoride for 30 days or more within the last 24 months
  • Rheumatoid arthritis or any other inflammatory arthritis
  • History of osteogenesis imperfecta, multiple myeloma, or Paget's disease
  • Active primary hyperparathyroidism
  • History of uveitis, iritis, or chronic conjunctivitis
  • History of retinopathy or nephropathy, especially in the presence of uncontrollable IDDM (Hb1AC > 10%)
  • AST or ALT > 2X the upper limit of normal
  • ALP > 1.5X the upper limit of normal
  • Serum creatine > 2 mg/dl
  • Creatine clearance < 40 ml/min
  • Serum calcium > 11.0 mg/dL and < 8mg/dL
  • Serum 25(OH)D < 15 ng/ml
  • In subjects with HIV must have a plasma HIV-1 RNA level of < 5000, a CD4+ count of > 100 cells/mm3m and be receiving stable ART for a minimum of 12 weeks prior study entry, with no plan at study entry to significantly alter ART
  • Allergy to zoledronic acid
  • Severe dental problems or current dental infections or with recent or impending dental surgery within three months of dosing
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01218035

Locations
Finland
Turku University Hospital
Turku, Finland, 20520
Sponsors and Collaborators
Turku University Hospital
Academy of Finland
Novartis
Stryker Nordic
Investigators
Principal Investigator: Hannu T Aro, MD, PhD Turku University Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Professor Hannu T Aro, MD, PhD, Turku University Hospital
ClinicalTrials.gov Identifier: NCT01218035     History of Changes
Other Study ID Numbers: 94/180/2006
Study First Received: October 7, 2010
Last Updated: June 15, 2011
Health Authority: Finland: National Agency for Medicine

Keywords provided by Turku University Hospital:
Hip osteoarthritis
Bisphophonate therapy
Zoledronic acid
Radiostereometric analysis
Osteoporosis

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Hip
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014