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

February 10, 2017 updated by: Turku University Hospital

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Zoledronic Acid in Enhancement of Early Stability of Cementless Primary Hip Prosthesis

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Finland
      • Turku, Finland, 20520
        • Turku University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
RSA outcome, functional recovery and metabolic treatment response
Time Frame: 12 months
  • 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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Turku University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Novartis
Academy of Finland
Stryker Nordic

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hannu T Aro, MD, PhD, Turku University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 7, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 8, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 13, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 10, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 94/180/2006

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