E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prosthetic loosening of hip and knee arthroplasty |
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E.1.1.1 | Medical condition in easily understood language |
Joint replacements of the hip and knee becoming loose |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The ultimate purpose of the study is to investigate if postoperative bisphosphonate treatment can reduce the risk of late prosthetic loosening in patients operated with primary hip- and knee arthroplasty due to osteoarthritis. |
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E.2.2 | Secondary objectives of the trial |
To investigate if peroperative bisphosphonate treatment affects radiographic outcome variables at 3 and 6 years after the index surgery.
Other secondary objectives are changes in KOOS/HOOS from baseline to 6 years and SF36 at 1, 3 and 6 years. In exploratory analyses we aim to analyze subgroups for gender and implant types. We will also analyze the distribution of the KOOS and HOOS questionnaire to explore if the control group contains a higher proportion of patients with a poor result.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients eligible for a primary hip or knee prosthesis for any form of osteoarthritis, at all ages between 18 and 80. |
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E.4 | Principal exclusion criteria |
• Previous or present use of bisphosphonates or other antiresorptives • Present use of other drugs which influence bone, e.g. anti-osteoporotic agents glucocorticoids (more than 5mg per day), anti-epileptics, or use less than a year before randomization • Present use of nephrotoxic medication • Active malignant disease • Pregnancy and breast feeding • Previous radiation therapy • Metabolic disease (other than osteoporosis) affecting the skeleton • Rheumatic disease • Hypocalcemia as defined by local lab criteria • Simultaneous bilateral surgery • Communication problems (drug abuse, language or behavior problems) • Creatinine clearance (GFR) <35 mL/min • Regular use of corticosteroids more than 5 mg dexamethasone per day. • Atypical fracture or osteonecrosis of the jaw • Expected follow-op period less than 3 years (e.g. due to uncontrolled malignancy) • Expected to require special postoperative surveillance due to increased surgical risk (e.g. for cardiac, psychiatric condition) • Participation in another clinical trial involving medication within 30 days
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: Change in KOOS/HOOS from baseline until 3 year follow up. The treatment effect will also be estimated separately for knee and hip implants as part of explanatory analyses. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The main secondary objective is to evaluate signs of radiographic loosening at 3 and 6 years. Other secondary objectives are changes in KOOS/HOOS from baseline to 6 years and SF36 at 1, 3 and 6 years. In exploratory analyses we aim to analyze subgroups for gender and implant types. We will also analyze the distribution of the KOOS and HOOS questionnaire to explore if the control group contains a higher proportion of patients with a poor result.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 and 6 years after the index surgery |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial is ended when the the last patient has undergone radiographic assessment at 6 years and completed all evaluation forms. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |