Hip OsteoarthritisPhase 4NCT01218035
Efficacy of Zoledronic Acid in Enhancement of Early Stability of Cementless Primary Hip Prosthesis
A Phase 4 study testing zoledronic acid in people with Hip Osteoarthritis, run by Turku University Hospital at 1 site in Finland.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Hip Osteoarthritis
- What is being tested?
- zoledronic acid
- Type of treatment
- Injection or infusion
- How many people
- 49 participants
- Where
- 1 siteFinland
- Study dates
- May 2007to Jun 2011
- Phase
- Phase 4
- 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 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Degenerative hip osteoarthritis as the indication for hip replacement
- Postmenopausal female patient
- Age of at least 20 years
- Signed Informed Consent
Who cannot join
- 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:
Show all 24Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Hip Osteoarthritis
- Being tested
- zoledronic acid
- Keywords
- Hip osteoarthritis, Bisphophonate therapy, Zoledronic acid, Radiostereometric analysis, Osteoporosis
- Medical subject headings
- Osteoarthritis, Hip, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zoledronic acidDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this study is to test whether a single infusion of zoledronic acid reduces periprosthetic bone loss measured by DXA.
Measured: 12 months
Secondary outcomes (1)
RSA outcome, functional recovery and metabolic treatment response
- 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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2010 (estimated)
- Study startMay 2007
- Primary completionDec 2010
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hip OsteoarthritisStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Collaborators
- Academy of Finland, Novartis, Stryker Nordic
- Responsible party
- Sponsor
- Investigators
- Hannu T Aro, MD, PhD, Principal investigator, Turku University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01218035
- Sponsor's protocol ID
- 94/180/2006
- Status last verified
- Feb 2017
- First submitted
- 7 Oct 2010
- Last updated
- 13 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Makinen TJ, Alm JJ, Laine H, Svedstrom E, Aro HT. The incidence of osteopenia and osteoporosis in women with hip osteoarthritis scheduled for cementless total joint replacement. Bone. 2007 Apr;40(4):1041-7. doi: 10.1016/j.bone.2006.11.013. Epub 2007 Jan 17.
PubMed 17239668Makinen TJ, Koort JK, Mattila KT, Aro HT. Precision measurements of the RSA method using a phantom model of hip prosthesis. J Biomech. 2004 Apr;37(4):487-93. doi: 10.1016/j.jbiomech.2003.09.004.
PubMed 14996560Alm JJ, Makinen TJ, Lankinen P, Moritz N, Vahlberg T, Aro HT. Female patients with low systemic BMD are prone to bone loss in Gruen zone 7 after cementless total hip arthroplasty. Acta Orthop. 2009 Oct;80(5):531-7. doi: 10.3109/17453670903316801.
PubMed 19916684
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01218035
- Acronym / sponsor ID
- 94/180/2006
- Conditions
- Hip Osteoarthritis
- Keywords
- Hip osteoarthritis, Bisphophonate therapy, Zoledronic acid, Radiostereometric analysis, Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Turku University HospitalOther government
- Collaborators
- Academy of Finland, Novartis, Stryker Nordic
- Study start
- May 2007
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 8 Oct 2010 (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.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Degenerative hip osteoarthritis as the indication for hip replacement
- Postmenopausal female patient
- Age of at least 20 years
- Signed Informed Consent
Key exclusion criteria (24 listed)
- 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
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 acidThe 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. | Drug | – |
Primary outcome
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
1 secondary outcome
RSA outcome, functional recovery and metabolic treatment response
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2017.
- Background: PubMed 17239668Makinen TJ, Alm JJ, Laine H, Svedstrom E, Aro HT. The incidence of osteopenia and osteoporosis in women with hip osteoarthritis scheduled for cementless total joint replacement. Bone. 2007 Apr;40(4):1041-7. doi: 10.1016/j.bone.2006.11.013. Epub 2007 Jan 17.
- Background: PubMed 14996560Makinen TJ, Koort JK, Mattila KT, Aro HT. Precision measurements of the RSA method using a phantom model of hip prosthesis. J Biomech. 2004 Apr;37(4):487-93. doi: 10.1016/j.jbiomech.2003.09.004.
- Background: PubMed 19916684Alm JJ, Makinen TJ, Lankinen P, Moritz N, Vahlberg T, Aro HT. Female patients with low systemic BMD are prone to bone loss in Gruen zone 7 after cementless total hip arthroplasty. Acta Orthop. 2009 Oct;80(5):531-7. doi: 10.3109/17453670903316801.
- Orthopaedic Research UnitLink provided by the sponsor.
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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.
Hannu T Aro, MD, PhD principal investigator
Turku University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing zoledronic acid in people with Hip Osteoarthritis, run by Turku University Hospital at 1 site in Finland.
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 4 inclusion and 24 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: finished, as of the sponsor's last update on 13 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01218035, which also lists 3 linked publications.
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 13 Feb 2017.