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Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women (ProliaHip)

Primary Purpose

Hip Osteoarthritis

Status
Completed
Phase
Phase 4
Locations
Finland
Study Type
Interventional
Intervention
Denosumb
Placebo (for denosumab)
Sponsored by
Turku University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hip Osteoarthritis focused on measuring Denosumab, Osteoporosis, Hip replacement, Osteoarthritis, Radiostereometric analysis (RSA), Dual energy X-ray absorptiometry (DXA)

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Postmenopausal women, age: ≥ 60 years to ≤ 85 years at randomization
  • Degenerative primary hip osteoarthritis as the indication of hip replacement
  • Signed informed consent

Exclusion Criteria:

  • Presence of severe osteoporosis (T-score less than -4.0 and a previous fracture)
  • Presence of Dorr C-type geometric change of the proximal femur
  • Evidence of secondary osteoporosis
  • Clinical or laboratory evidence of hepatic disease
  • Laboratory evidence of hypocalcaemia
  • Vitamin D deficiency (serum 25-OH(D) < 12 ng/mL)
  • Disorders of parathyroid function
  • Uncontrolled hyperthyroidism or hypothyroidism
  • History of malignancy, radiotherapy or chemotherapy for malignancy (except basal cell carcinoma of the skin) within the last 5 years
  • History of osteonecrosis of the jaw
  • History of recent tooth extraction or other dental surgery and/or invasive dental work planned in the next 2 years
  • Severe asthma or chronic obstructive pulmonary disease
  • History of solid organ or bone marrow transplant

  • Use within 12 months of drugs that affect bone metabolism such as ant-osteoporotic agents (including SERMS), estrogens, testosterone, and anti-epileptics:

    • Cumulative dose of 500 mg prednisone or equivalent within the last 6 months
    • Ever use of oral or iv bisphosphonates
    • Ever use of strontium ranelate or fluoride

  • Use of the following medications:

    • chronic systemic ketoconazole
    • androgens
    • cinacalcet
    • aluminum
    • lithium
    • protease inhibitors
    • gonadotropin-releasing hormone agonists
  • Rheumatoid arthritis or any other inflammatory arthritis
  • History of skeletal disorder, such as Paget's disease or osteomalacia
  • Alcohol abuse

  • General

    • Mental, neurological or other conditions that may affect the ability to perform functional or clinical assessments required by the protocol
    • Subjects with known sensitivity or intolerance to any of the products to be administered (calcium and D-vitamin supplements, denosumab)
    • Subject will not be available for protocol-required study visits, to the best of the subject's and investigator's knowledge
    • Any other condition that, in the judgement of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

Sites / Locations

  • Turku University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Denosumab

Placebo

Arm Description

Subcutaneous injection of denosumab 60 mg 4 weeks before surgery and 22 weeks after surgery

Subcutaneous injection of placebo 4 weeks before surgery and 22 weeks after surgery

Outcomes

Primary Outcome Measures

Periprosthetic bone mineral density (BMD)
Periprosthetic BMD of the proximal femur will be measured according to seven Gruen zones and compared with the baseline value

Secondary Outcome Measures

Radiostereometric analysis (RSA) of prosthesis stem migration
The translatory and rotatory migration of the femoral stem will be measured by means of model-based RSA and compared with the position at the baseline

Full Information

First Posted
August 16, 2013
Last Updated
April 26, 2018
Sponsor
Turku University Hospital
Collaborators
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT01926158
Brief Title
Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women
Acronym
ProliaHip
Official Title
Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women: a Randomized, Double-blind, Placebo-controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
December 2013 (Actual)
Primary Completion Date
February 4, 2017 (Actual)
Study Completion Date
December 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Turku University Hospital
Collaborators
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized clinical trial will evaluate the efficacy of an antiresorptive osteoporosis drug (denosumab) in prevention of periprosthetic bone loss and in promotion of implant osseointegration (bone bonding) in postmenopausal women after total hip replacement. The investigators assume that denosumab prevents periprosthetic bone loss and enhances bone bonding of the hip stem in postmenopausal women.
Detailed Description
This is a randomized, double-blind and placebo-controlled trial to evaluate the efficacy of denosumab on the biologic incorporation of cementless hip prosthesis. The study population consists of sixty-eight postmenopausal female patients, who are scheduled to have cementless total hip replacement (THA) for primary hip osteoarthritis. The patients will be randomly assigned to receive a subcutaneous injection of denosumab 60 mg or placebo four weeks before surgery and 22 weeks after surgery. The primary hypothesis is that denosumab is effective in preventing periprosthetic bone loss in the proximal femur as measured by DXA. The secondary hypothesis is that denosumab is effective in enhancement of bone bonding (osseointegration) of cementless femoral stems, as measured by model-based radiostereometric analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hip Osteoarthritis
Keywords
Denosumab, Osteoporosis, Hip replacement, Osteoarthritis, Radiostereometric analysis (RSA), Dual energy X-ray absorptiometry (DXA)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Denosumab
Arm Type
Experimental
Arm Description
Subcutaneous injection of denosumab 60 mg 4 weeks before surgery and 22 weeks after surgery
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subcutaneous injection of placebo 4 weeks before surgery and 22 weeks after surgery
Intervention Type
Drug
Intervention Name(s)
Denosumb
Other Intervention Name(s)
Brand name: Prolia
Intervention Description
Prefilled syringe of 1 mL denosumab solution
Intervention Type
Drug
Intervention Name(s)
Placebo (for denosumab)
Other Intervention Name(s)
Prefilled syringe of 1 mL placebo solution
Primary Outcome Measure Information:
Title
Periprosthetic bone mineral density (BMD)
Description
Periprosthetic BMD of the proximal femur will be measured according to seven Gruen zones and compared with the baseline value
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Radiostereometric analysis (RSA) of prosthesis stem migration
Description
The translatory and rotatory migration of the femoral stem will be measured by means of model-based RSA and compared with the position at the baseline
Time Frame
48 weeks
Other Pre-specified Outcome Measures:
Title
Functional recovery
Description
To investigate if the enhanced incorporation of hip prostheses in denosumab treated patients compared to placebo leads to faster functional recovery as measured by main parameters of gait analysis, pedometer evaluation of walking activity and patient reported outcome measures
Time Frame
48 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Postmenopausal women, age: ≥ 60 years to ≤ 85 years at randomization Degenerative primary hip osteoarthritis as the indication of hip replacement Signed informed consent Exclusion Criteria: Presence of severe osteoporosis (T-score less than -4.0 and a previous fracture) Presence of Dorr C-type geometric change of the proximal femur Evidence of secondary osteoporosis Clinical or laboratory evidence of hepatic disease Laboratory evidence of hypocalcaemia Vitamin D deficiency (serum 25-OH(D) < 12 ng/mL) Disorders of parathyroid function Uncontrolled hyperthyroidism or hypothyroidism History of malignancy, radiotherapy or chemotherapy for malignancy (except basal cell carcinoma of the skin) within the last 5 years History of osteonecrosis of the jaw History of recent tooth extraction or other dental surgery and/or invasive dental work planned in the next 2 years Severe asthma or chronic obstructive pulmonary disease History of solid organ or bone marrow transplant Use within 12 months of drugs that affect bone metabolism such as ant-osteoporotic agents (including SERMS), estrogens, testosterone, and anti-epileptics: Cumulative dose of 500 mg prednisone or equivalent within the last 6 months Ever use of oral or iv bisphosphonates Ever use of strontium ranelate or fluoride Use of the following medications: chronic systemic ketoconazole androgens cinacalcet aluminum lithium protease inhibitors gonadotropin-releasing hormone agonists Rheumatoid arthritis or any other inflammatory arthritis History of skeletal disorder, such as Paget's disease or osteomalacia Alcohol abuse General Mental, neurological or other conditions that may affect the ability to perform functional or clinical assessments required by the protocol Subjects with known sensitivity or intolerance to any of the products to be administered (calcium and D-vitamin supplements, denosumab) Subject will not be available for protocol-required study visits, to the best of the subject's and investigator's knowledge Any other condition that, in the judgement of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hannu T Aro, MD, PhD
Organizational Affiliation
Turku University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Turku University Hospital
City
Turku
ZIP/Postal Code
20521
Country
Finland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22489886
Citation
Aro HT, Alm JJ, Moritz N, Makinen TJ, Lankinen P. Low BMD affects initial stability and delays stem osseointegration in cementless total hip arthroplasty in women: a 2-year RSA study of 39 patients. Acta Orthop. 2012 Apr;83(2):107-14. doi: 10.3109/17453674.2012.678798. Epub 2012 Apr 11.
Results Reference
background
PubMed Identifier
21074160
Citation
Moritz N, Alm JJ, Lankinen P, Makinen TJ, Mattila K, Aro HT. Quality of intertrochanteric cancellous bone as predictor of femoral stem RSA migration in cementless total hip arthroplasty. J Biomech. 2011 Jan 11;44(2):221-7. doi: 10.1016/j.jbiomech.2010.10.012. Epub 2010 Nov 11.
Results Reference
background
PubMed Identifier
19916684
Citation
Alm 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.
Results Reference
background
PubMed Identifier
17239668
Citation
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.
Results Reference
background
PubMed Identifier
14996560
Citation
Makinen 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.
Results Reference
background
PubMed Identifier
27334320
Citation
Nazari-Farsani S, Finnila S, Moritz N, Mattila K, Alm JJ, Aro HT. Is Model-based Radiostereometric Analysis Suitable for Clinical Trials of a Cementless Tapered Wedge Femoral Stem? Clin Orthop Relat Res. 2016 Oct;474(10):2246-53. doi: 10.1007/s11999-016-4930-0. Epub 2016 Jun 22.
Results Reference
result

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Denosumab in Enhancement of Bone Bonding of Hip Prosthesis in Postmenopausal Women

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