Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02404727 |
| Other study ID # |
Holstebro Hospital |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 2014 |
| Est. completion date |
March 2018 |
Study information
| Verified date |
December 2014 |
| Source |
University of Aarhus |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The aim of this project is to investigate prosthesis fixation in the bone, respectively
cemented and uncemented operation method of Avantage® dual-mobility acetabular cup in elderly
patients, wear of the plastic in dual-mobility hip prosthesis and evaluate the clinical
function, patient satisfaction and possible complications.
Patients included in this study suffer from osteoarthritis of the hip.
Description:
The Elderly Hip Patient The proportion of elderly in the Danish population is increasing and
their and functional level is generally good, despite other health problems, which
intensifies the demand for a primary definitive (one-stage) and safe surgical treatment in
case of osteoarthritis or fragility low-energy displaced femoral neck fracture. Total hip
arthroplasty (THA) is one of the most successful procedures in modern orthopaedic surgery to
achieve pain relief and restore normal walking ability in a preoperative painful and stiff
hip joint.
Bone Quality and THA surgical technique Osteoporosis (brittle bones) is defined as a chronic
systemic skeletal disease characterized by low bone mineral density (osteopenia) and
microarchitecture changes in the trabecular bone structure resulting in reduced strength and
therefore increased risk of fractures. Among Danish women over 65 years of age, the
prevalence of osteoporosis is 40-60%, and the prevalence among men is increasing. Much effort
is put into secondary fracture prophylaxis such as vitamin D and calcium as well as medical
bone anti-resorptive treatment (i.e. bisphosphonates).
When the bone is weak/osteoporotic there is a general but undocumented recommendation of
cemented over uncemented THA fixation. It has been shown that uncemented hip stems migrate
more than cemented components in osteopenic and osteoporotic bone wherefore cemented stem
fixation is recommended. However, Danish hip surgeons favour uncemented fixation even in the
fragile and osteoporotic elderly because it reduces the surgical time, minimizes the risk of
intraoperative cement disease/fat embolism and dead, and makes revision surgery in case of
infection or peri-prosthetic fracture easier to re-operate. In 2012, 7364 acetabular cups
were inserted uncemented versus 1015 uncemented - for all indications for THA in Denmark.
Reoperation of the same hips within 2 years after primary THA due to new femoral neck
fracture or complications following treatment of proximal femoral fracture was 4.7 %. There
is clinical conviction that cemented cups are easier to place in the correct inclination and
anteversion position. However, due to the posterior-lateral overhang of dual mobility cups
the postero-lateral edge-cementation is likely to be insufficient leading to micromotion and
aseptic loosening. In the clinical experience this is a lesser risk with cementless cups.
Compared to other Nordic countries, Denmark has the lowest incidence of aseptic cup loosening
of 34.8% and respectively 47.3% and 50.4% for Norway and Sweden. The reason for revision due
to dislocation is 33.5% in Denmark compared to Norway and Sweden, respectively 23.8% and
23.4% and may be related to an overall difference in surgical approach (postero-lateral
approach in Denmark but antero-lateral approach in Norway and Sweden). Approximately 96% are
operated with posterior approach in Denmark whereas 23.8% and 60.3% were operated by
posterior approach in Norway and Sweden, respectively.
Dual-mobility articulation concept In 1974 Professor Bousquet developed the dual-mobility
(DM) hip articulation concept to reduce wear, restore near-normal motion-range in the hip
joint, and at the same time increase hip prosthesis stability. The dual-mobility hip
articulation design consist of a large non-fixed polyethylene liner sliding freely within the
metal cup-shell which is fixed into the bone, and inside the mobile liner is a second
articulation with a small femoral head. The dual-articulation of the prosthetic joint
prevents impingement of the femoral neck on the acetabular rim of the implant. Studies have
shown that dual-mobility hip prostheses have good survival rates and reduces dislocation
rates both in patients with primary osteoarthritis of the hip and a lesser compliant patient
group with displaced femoral neck fractures . Clinical expectations for the dual-mobility
articulation concept for treatment of displaced medial FNF are good; however, there are only
a few publications available and there are no studies of implant fixation / cup migration. It
is important to study both the dislocation risk as well as the mechanical stability of the
bony fixation since the advantage of a low dislocation rate would be meaningless if the cups
were to loosen mechanically from the surrounding bone in the mid- or longer term.
Femoral Neck Fracture and THA THA may be used as the primary treatment option for displaced
medial femoral neck fractures (FNF). Compared to screw osteosynthesis, THA results in a
stable fracture treatment with less post-operative pain and faster mobilization after
displaced medial FNF and with fewer complications. The most common complication to THA
treatment in old and perhaps memory-impaired patients is dislocation instability. At the
Regional Hospital Holstebro our results with the Saturne® Dual-Mobility THA in this patient
group (n>500) during the last 7 years propose the risk of THA hip dislocation in high-risk
patients to be below 5%. In 2012, 10,309 patients were admitted to Danish hospitals with
femoral fractures. Approximately 600 of these hip fracture patients were treated with THA.
Patients with hip fractures are very resource intensive and require approximative 2.2% of all
hospital bed days in Denmark. Furthermore, these elderly, with an average age of 80 years and
a high co-morbidity percentage also have a high mortality risk of approximately 10% within
the first 30 days after FNF. The one-year mortality is 15-25%. Reoperations frequency depends
on the fracture type and operative treatment, and varies from a few per cent after insertion
of THA to 25% after osteosynthesis. Often it is the acute and chronic medical conditions that
cause the elderly to low energy falls resulting in hip fracture, but it may also just be
accidental and related to osteoporosis.
Radiostereometric Analysis (RSA) Mechanical loosening of the prosthesis may be suspected if
the prosthesis migrates relative to underlying and adjacent bone. Therefore, there is now a
consensus that the introduction of new prostheses and new operational methods of prosthesis
insertion should be evaluated through migration studies before they can be recommended for
use in general. Clinical studies have shown a high predictive power between early migration
of joint prostheses and later prosthesis loosening and premature revision. Radiostereometric
analysis (RSA) is a very accurate method for assessment of cup migration at precision levels
0.11 mm precision or better.
Dual Energy X-ray Absorptiometry (DXA) The clinical survival of joint prostheses depends on
the quality of the surrounding bone and bone mineral density (BMD) is an important measure of
bone strength and quality. The periprosthetic bone density can be measured with Dual Energy
X-ray Absorptiometry (DXA), which is a precise method for measuring even small changes in BMD
around hip prostheses. Patients are exposed to a very little dose of radiation with these
studies and scanning only takes a few minutes. Typically, four to five scans are taken during
a 2 to 5 year follow-up. For assessment of the bone surrounding the acetabular cup the 3
DeLee zones or the 4 Wilkinson Zones are often used, and Gruen zones are used for assesment
around the stem.
Bone density is defined by a and in osteopenic bone the T-score is between <1.0 - > 2.5,
whereas when osteoporotic the T-score is < 2.5 and severe osteoporosis < 4.0.
It is possible to register bone resorption around implants with DXA before resorption becomes
visible on conventional x-ray films in the form of "radiolucent lines" (RLL). It is important
to monitor remodelling in the periprosthetic bone because decreasing BMD may weaken the
prosthetic fixation and lead to failure. It is known that BMD decreases initially after
implant surgery and then stabilize after a periode of a few years.
Polywear The acetabular plastic component polyethylene (PE) wear particles stimulate a
biologic response with production of various inflammatory mediators, which stimulate
migration of leucocytes into tissues and activate collagen synthesis, and stimulate
osteoclasts to resorb bone and contribute to osteolysis.
Reports have suggested that hydroxyapatite (HA) coated implants that are used in cementless
hip replacements further contribute to inferior survival of medium- thickness spray-dried
HA-coated cups with individual cases of excessive PE wear and premature cup failure.
The concept of the dual-mobility cup provides a theoretical question whether the double
articulations leads to more wear and hence earlier revision, especially in younger more
active patients.
It has previously been shown that a two-dimentional (2D) wear of the polyethylene of 0.1 mm /
year may lead to osteolysis and loosening of the prosthetic components, which deteriorates
prosthesis durability.
Wear of hip prostheses polyethylene can be accurately measured (0.09 mm) with software
PolyWare 3D Pro Digital Version on digital clinical antero-posterior radiographs of the hip
prosthesis.
Study design and methods Comparison of prosthesis migration of cemented versus uncemented
dual-mobility cup fixation Objective: Investigate prosthesis migration and polyethylene wear
of cemented and cementless Avantage® dual-mobility acetabular components (Biomet Inc.) in
elderly patients and correlate migration measurements with radiological evaluation of implant
placement/cementation quality, with bone quality at the time of surgery
(osteoporotic/osteopenic/normal bone), and with functional outcome after two years. The
migration pattern and magnitude will predict the likelihood of later aseptic loosening and
revision.
Design:
Prospective randomized patient-blinded clinical trial.
Hypotheses:
1. More stable fixation of cemented compared with uncemented cups (initially and between
1-2 years).
2. Acceptable cement coverage at the postero-lateral acetabular rim in most (95%) of cases.
3. Low polyethylene wear-rate (<0.1mm/year after bedding-in during the first 3 months).
4. Similar periprosthetic pelvic bone loss (Wilkinson zones) irrespective of fixation
method.
5. Low dislocation risk irrespective of fixation method (<1%).
6. Patient satisfaction >90% in general.
Patients:
The Avantage® cup is used for all elderly patients on our department including patients with
displaced medial FNF and patients with primary osteoarthritis. It may also be used for
revision surgery in case of dislocation complications. Acute patients with FNF are difficult
to include in studies when some pre-study investigations are necessitated and further
patients with FNF are difficult to inform (pain and morphine drugged) and it is difficult to
give proper time to consider study participation and perhaps call for an assessor to help
make the decision. A big drop out due to difficult circumstances about project-information
and consent could be a serious selection bias and could also prolong the inclusion period
seriously. Mortality in FNF patients is high and poses a risk of many patients lost to
follow-up during a 5-year study period and therefore demands a high estimated sample size.
Therefore this study applies only to elderly elective patients with osteoarthritis scheduled
for elective THA. All patients >70 years of age with osteoarthritis of the hip, who are
candidates for a total hip prosthesis, will be offered participation in the study. All
patients will be operated by one of two experienced hip surgeons and they will follow the
usual postoperative regime at Holstebro Regional Hospital (pain treatment, physiotherapy and
full weight bearing, thromboembolic and antibiotic prophylaxis). All eligible patients will
be registered, those who choose not to participate, will be asked for the reason of refusal,
to be able to detect possible selection bias.
INFORMED CONSENT The first contact is made in the outpatient clinic of orthopaedic department
of Regional Hospital Holstebro, where the patients will be seen by one of two orthopaedic
surgeons experienced in total hip replacement surgery.
With the first contact, the patients will receive oral and written information about the
study. During this contact it is possible for the patient to have an extra person along. If
requested by the patient/needed for decision-making concerning study participation, we will
offer second project information to the patient with the option to bring an assessor.
Patients can decide to participate in the study up to a week before surgery, where they will
come to the information day prior to surgery, which is a part of the normal fast-track
program. There is an average waiting period between first contact and surgery of 4 weeks,
which means that patients have 3 weeks to decide. Written informed consent will be obtained
before commencement of data collection, at the latest on the information day prior to
surgery. When the consent form is signed DXA scanning and filling out questionnaires will
commence, and post-operative stereoradiographs and DXA scans will be booked.
Method:
All patients will be DXA scanned pre-operatively for measurements of general bone mineral
density and classification in a) normal bone, b) osteopenia) or c) osteoporosis. Patients
with a T-score above -2.5 (normal bone and osteopenic bone) will be grouped and patients with
a T-score at or below -2.5 and at or above - 4.0 will be grouped (osteoporosis). Patients
will be stratified to the two treatment modalities (cemented acetabular cup fixation and
cementless acetabular cup fixation) according to this dichotomy on T-score. Patients with a
new diagnosis of osteoporosis will be referred to their own general practitioner concerning
blood work and initiation of anti-resorptive treatment. On going medical treatment for
osteoporosis will be recorded. After stratification according to T-score, patients are
randomized during surgery with a cemented or cementless Avantage® dual-mobilty Cup (Biomet
Inc.) and patients will be blinded with respect to implant fixation method. The Avantage® Cup
can be inserted both cemented and uncemented where the cementless are HA coated and cemented
cups are fully polished. The liner is gamma irradiated to induce a high level of crosslinking
and Vitamin E is infused into the highly crosslinked polyethylene. A 28-mm chrome-cobalt
femoral head will be used in all cases. The femoral stems will be similar in all patients
(cemented Exeter stems, Stryker® Inc.) and Palacos® bone cement (Heraeus Medical inc.) will
be used. During surgery 1mm tantalum beads are inserted in the bone surrounding the
prosthetic components (both the femur and the cup) allowing for post-operative migration
measurements with RSA.
Postoperative, 3 months, 1 year, 2 years and 5 years after surgery the patients are followed
with:
- Stereo radiographs (cup migration and polyethylene wear).
- Standard radiographs (evaluation of cup position (PolyWare software) and evaluation of
cementation quality)
- DXA scan at follow-up to measure changes in the peri prosthetic bone density (Wilkinson
Zones in the acetabulum and Gruen Zones around the stem).
- Collection of PROM (Osteoporosis risk assessment, Oxford Hip Score,EuroQol-5D (EQ-5D),
Harris Hip Score, VAS score at rest and activity).
- Activity measurement with an accelerometer 2 weeks test prior to each control.
Power and data analysis: The proximal cup migration was used as the primary effect variable
in the pre-study power analysis based on a pilot study including both cemented and cementless
Avantage DM cups. Sample size calculation using two-sample mean test for a minimal relevant
difference of 0.2mm with a mean cup migration of 0.1mm and a standard deviation of 0.2 (pilot
study), power of 0.90, and 5% risk of type-1 error, 23 patients were needed in each group. To
compensate for potential dropouts, we decided to include 30 hips in each treatment arm.
Secondary endpoints are polyethylene wear, activity, complications, and functional outcome by
clinical examination (HHS) and PROM (OHS, EQ5D). All of the applied methodologies are
available, accessible and validated at Holstebro Regional Hospital.
The Helsinki II agreement will be followed. The study plan will be registered at
clinicaltrails.gov. Application for permission for a database will be submitted to the Data
Protection Agency of the region Midtjylland and data will be stored in accordance with
applicable law.
Ethics and (dis) advantages for the patient There are only a few publications available on
implant fixation in elderly patients and currently only for fixation of the stem in patients
with normal bone or osteoporotic bone. There are no RSA studies available on the Avantage®
cup even though it is the standard cup in most Danish Orthopaedic Departments and one of the
cups available in the Middle Region Implant Supply. The Avantage® cup is available in a
similar design for cemented and cementless fixation principle. The dual-mobility concept is
well proven in different implant brands over 35 years with good results on revision and
dislocation (both very low) but no RSA studies on fixation are available. The current study
may therefore add important and new knowledge to the literature. It is important to study
both the dislocation risk as well as the mechanical stability of the bony fixation since the
advantage of a low dislocation rate would be meaningless if the cups were to loosen
mechanically from the surrounding bone in the mid- or longer term.
The study will reveal insight into whether the cemented or the cementless fixation principle
is better for elderly patients and if there is a difference based on systemic and
periprosthetic bone mineral density. Furthermore compiled prosthesis migration with the bone
quality, accelerometer tests, and the incidence of complications that could contribute to the
improvement of hip prosthesis surgery to such an extent that clearly outweighs the side
effects associated with the study.
The study will be performed using the fast-track program of the department, ensuring the same
length of stay for both groups, and no additional admission days are added as compared to
other patients who undergo hip prosthesis surgery. Patients have minimal increased radiation
dose compared to the usual control regime after hip replacement surgery. Written and informed
consent is required. The local research ethics committee must approve the study before
initiation.
Measurements were taken for the radiation dose, which shows that the stereo x-ray of the hip
provides a very low radiation dose of 0.15 mSv.. DXA measurements of the femur or spine
(osteoporosis control) produce an effective dose equivalent to 292 millisievert (milliSv) and
a scan around the hip implants produce an effective dose of 146 milliSv (info from General
Electric (GE) scanner manufacturer). A conventional radiograph of the hip provides a dose of
0.85 milliSv. Patients, who undergo hip prosthesis surgery outside the protocol in our
hospital unit, have one conventional radiograph after surgery and, as of recently, no
clinical or radiographic later follow-up due to necessary cuts on budget-costs. Patients in
this study have one conventional radiograph post-operatively and one conventional x-ray at 2
years and 5 years follow-up. In total the project patients are subjected to an additional
radiation dose of 2 conventional radiographs (1.7 mSv), 1 osteoporosis assessment (0.03 mSv),
seven times periprosthetic DXA scans including double measurements (0.1 mSv) and six times
the stereo radiography including double measurements (0.9 mSv). Patients included in this
study get exposed to an additional radiation dose of 2.73 mSv. This corresponds to
approximately 3 conventional radiographs of the hip, and it provides an additional risk of
fatal cancer of 0.01%. This places the subjects in group IIb., where the overall risk of the
irradiated individual is 1 to 10,000.
No financial support/compensation will be offered to patients for study participation.
Regarding compensation and remuneration after death or injury of a project participant
reference is to the national patient insurance program.
Publication of results The project is part of a Doctor of Philosophy (Ph.D.) project
concerning treatment of dislocated Garden I and II femoral neck fracture with a dual-mobility
arthroplasty concept. The Ph.D. protocol has been approved for enrollment at Aarhus
University Hospital during spring/summer 2014. All results, both positive and negative as
well as inconclusive, will be sought published in international scientific peer-reviewed
journals as well as presented on national and international scientific conferences. The
Vancouver rules for authorship will be followed. There is a mutual agreement that Steffan
Tábori Jensen will write the manuscript as the first author.
Previous RSA and research at Holstebro Regional Hospital The Orthopaedic Research Unit,
Regional Hospital Holstebro, has the needed technical research staff and academic research
expertise, the required experience and software/equipment, including server capacity and
software, to complete the study. Several articles in this area have been published emanating
from the department and its associates.
