E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoarthritis in the knee treated with cementless total knee arthroplasty |
Sligigt i knæleddet der behandles med ucementeret knæledsprotese |
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E.1.1.1 | Medical condition in easily understood language |
Osteoarthritis in the knee treated with cementless total knee arthroplasty |
Sligigt i knæleddet der behandles med ucementeret knæledsprotese |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023476 |
E.1.2 | Term | Knee osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 |
Investigate the possibility to improve immediate and long term fixation of cementless tibial components of total knee arthroplasty by use of adjuvant treatment by denosumab or topical zoledronic acid through assessment of implant migration in relation to the bone by radiostereophotogrammetric analysis (RSA) and assessment of bone mineral density changes in the periprosthetic bone as measured by dual energy x-ray absorptiometry (DXA).
H1: Tibial components are more stable (RSA) in the intervention groups receiving active substances (denosumab s.c. injection or topical zoledronic acid) compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
H2: The periprostetic bone is better conserved in proximity of tibial components when adjuvant treatment by denosumab or zoledronic acid is used as compared to placebo.
H3: Adjuvant treatment by denusomab will result in a systemic response whereas treatment with topical zoledronic acid and placebo will not result in a systemic response as measured by bone formation markers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- primary knee osteoarthritis in capable men and women
- sufficient bone quality for total cruxiate retaining knee arthroplasty
- age above 18 years but maximum 75 years of age
- informed and written consent
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E.4 | Principal exclusion criteria |
- neuromuscular or vascular disease in the affected leg
- peroperatively found to be unsuitable for a primary knee arthroplasty
- osteoporosis based on former diagnosis or preoperative DXA-scan
- fracture sequelae or previous PTO or previous extensive knee surgery
- need for a stem-elongation
- NSAID postoperatively
- pregnancy (positive pregnancy test) or at risk of becoming pregnant during the project (not using safe anti-conceptive agents like contraceptive pills, intra-uterine device (IUD), hormone depot injection, subdermal implantation of a contraceptive rod, hormone vaginal ring, transdermal depot hormone sticking plaster)
- metabolic bone disease
- rheumatoid arthritis
- renal failure (GFR < 30 ml/min)
- persistent hypocalcaemia
- allergic to bisphosphonate or denusomab
- sporadic or permanent need of systemic glucocorticoid treatment
- active cancer
- radiation or chemotherapy
- poor dental status (increased risk of jaw-necrosis with bisphosphonates/denusomab)
- high use of alcoholic beverages (women > 14, men > 21 units/week) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Implant migration (RSA) measured continuously from baseline to follow-up (MTPM) and estimation of Continuous MTPM (MTPM migration > 0.2 mm between 12 and 24 months of follow-up) according to Ryd et al. (Ryd et al., 1995).
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
First patient, first visit June 2013.
Last Patient, last visit November 2025. |
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E.5.2 | Secondary end point(s) |
DXA - Changes in Bone Mineral Density under the Tibial Tray and in proximity of the central stem.
Biomarkers - Bone resorption from baseline to follow-ups and correlation between bone density changes, biomarkers of bone resorption and implant migration
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
First patient, first visit June 2013.
Last Patient, last visit November 2025. |
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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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | No |
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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When a total of 100 patients have been included and operated, and trial treatment and 10 years follow-up have been completed. |
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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 | 13 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |