Overview
Sponsor-declared trial summary
Osteoarthritis in the knee treated with cementless total knee arthroplasty
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 assessm…
Key facts
- Sponsor
- Region Midtjylland
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Musculoskeletal Diseases [C05]
- Trial duration
- 12 Jan 2014 → ongoing
- Decision date (initial)
- 2024-07-10
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-514903-33-00
- EudraCT number
- 2012-004046-15
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
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.
Secondary objectives 1
- 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.
Conditions and MedDRA coding
Osteoarthritis in the knee treated with cementless total knee arthroplasty
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10023476 | Knee osteoarthritis | 10028395 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- 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
Exclusion criteria 17
- 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)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Implant migration (RSA) measured continuously from baseline to followup (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).
Secondary endpoints 2
- 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
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Zoledronic Acid Fresenius Kabi 4 mg/5 ml koncentrat till infusionsvätska, lösning
PRD10351337 · Product
- Active substance
- Zoledronic Acid Monohydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- TOPICAL
- Max daily dose
- 0.5 mg milligram(s)
- Max total dose
- 0.5 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- M05BA08 — ZOLEDRONIC ACID
- Marketing authorisation
- 29891
- MA holder
- FRESENIUS KABI AB
- MA country
- Finland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Prolia 60 mg solution for injection in pre-filled syringe
PRD3618669 · Product
- Active substance
- Denosumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 120 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- M05BX04 — -
- Marketing authorisation
- EU/1/10/618/001
- MA holder
- AMGEN EUROPE B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 2
SUB12581MIG · Substance
- Active substance
- Sodium Chloride
- Pharmaceutical form
- INJECTION
- Route of administration
- TOPICAL
- Max daily dose
- 18 mg milligram(s)
- Max total dose
- 18 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12581MIG · Substance
- Active substance
- Sodium Chloride
- Pharmaceutical form
- INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 9 mg milligram(s)
- Max total dose
- 18 mg milligram(s)
- Max treatment duration
- 12 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Region Midtjylland
- Sponsor organisation
- Region Midtjylland
- Address
- Palle Juul-Jensens Boulevard 99
- City
- Aarhus N
- Postcode
- 8200
- Country
- Denmark
Scientific contact point
- Organisation
- Region Midtjylland
- Contact name
- Department of Orthopedics
Public contact point
- Organisation
- Region Midtjylland
- Contact name
- Department of Orthopedics
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Aarhus Universitet ORG-100028380
|
Aarhus N, Denmark | On site monitoring |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruitment ended | 107 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2014-01-12 | 2014-01-16 | 2017-02-14 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | PROTOKOL REGENEREX_UU | 5 |
| Protocol (for publication) | Summary of changes_RGX 10 yr | 1 |
| Recruitment arrangements (for publication) | Placeholder document_recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | Informeret samtykke til deltagelse i 10 ars kontrol | 1 |
| Subject information and informed consent form (for publication) | PATIENTINFORMATION REGENEREX_tillgsprotokol | 1 |
| Subject information and informed consent form (for publication) | PATIENTINFORMATION REGENEREX_tillgsprotokol_version 3_19022025 | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | Produktresume_prolia | 1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-21 | Denmark | Acceptable 2024-07-09
|
2024-07-10 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-03-26 | Denmark | Acceptable 2024-07-09
|
2025-03-26 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-04-04 | Denmark | Acceptable 2025-04-07
|
2025-04-07 |