Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02346513 |
| Other study ID # |
MD13036 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
November 24, 2014 |
| Last updated |
January 20, 2015 |
| Start date |
February 2014 |
| Est. completion date |
August 2015 |
Study information
| Verified date |
January 2015 |
| Source |
Korea University Guro Hospital |
| Contact |
Won Yong Shon, Professor |
| Phone |
+82.10.8908.6681 |
| Email |
shonwy[@]hotmail.com |
| Is FDA regulated |
No |
| Health authority |
Korea: Ministry of Food and Drug Safety |
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Primary objectives:
1. To measure serum metal ion levels (blood Chromium (Cr) and Cobalt (Co) ion
concentration) in patients that received the Ceramic on Metal arthroplasty of hip and
who have well functioning primary total hip arthroplasties during short and medium-
term follow up time points.
2. To compare blood ion levels of patient that received COM arthroplasty with the blood
ion levels of patient receiving non-COM standard total hip arthroplasty (a Metal on
polyethylene or ceramic on polyethylene total hip arthroplasty) at short- term and
medium-term follow up time points .
Secondary Objective:
1) To determine whether these blood levels correlate with any device specific factors such
as: component position, size and type, wear rate and/or patient specific factors such as
gender, body mass index, age and activity level.
Description:
Peri-prosthetic osteolysis is associated with aseptic loosening of a total hip replacement
(THR). It is understood to be a biological response to wear particles, with polyethylene
debris thought to be the major cause of the long-term failure.
With total hip replacement (THR) patients now being younger, more active younger, and
anticipating much greater longevity, reduced bearing wear becomes increasingly important.
Compared to the wear and osteolysis incidence with metal-polyethylene bearings, the
historical results of alternate bearings such as metal-on-metal (MOM) and ceramic-on-ceramic
(COC) generally showed much lower wear rates and osteolysis was seemingly quite rare. The
laboratory wear-rates for metal-metal bearings have generally fallen into the range 1-7
mm3/million cycles (Mc) and 0.1-1 mm3/Mc for run-in and steady-state phases, respectively.
Ceramic-on-ceramic and metal-on-metal bearing surfaces are often employed for total hip
replacement because of their resistance to wear. Alternative bearing surfaces such as
ceramic-on-ceramic and metal-on-metal eliminate polyethylene wear. Explanted metal-on-metal
articulations made of cobalt-chromium-molybdenum (Co-Cr-Mo) alloy have been shown to have
extremely low rates of linear wear, and ceramic-on-ceramic bearings even less. A
ceramic-on-ceramic articulation was first implanted in 1970 in France. Long-term reports
have shown excellent clinical results.
Ceramic-on-ceramic bearings have the advantage of low wear and high biocompatibility.
Alumina-ceramic particles are essentially insoluble in organic media and ionisation is
therefore unimportant. However, they have some limits: brittleness is a major concern for
ceramic, which could lead to clinically relevant failure rates (0.004% head fracture and
0.22% liner fracture. Although Metal-on-metal (MOM) articulations have been seen as one
potential solution to the problems associated with UHMWPE-induced osteolysis, metal ions
present in the serum and their potential toxic effects both locally and systemically are a
cause for concern.
A low wear rate is believed to be critical for extending the implant life of a prosthetic
joint, and wear volumes produced by MOM articulations have been estimated to be 40-100 times
lower than metal-on-polyethylene bearings. The wear of MOM prostheses is known to be highly
dependent upon the materials, tribological design and finishing technique. Clinical studies
of retrieved first and second-generation MOM hip prostheses have shown linear penetrations
of approximately 5 μm/year. This is equivalent to a wear volume of approximately 1 mm3/year,
two orders of magnitude lower than conventional polyethylene acetabular cups.
The observation that a small number of patients with first-generation MOM prostheses
exhibited good clinical and radiographical results after 20 years in vivo led to the
development of second-generation MOM hip prostheses, and in 1988 the Metasul prosthesis was
introduced into clinical practice. This comprised of a cobalt chrome alloy femoral head
articulating on a cobalt chrome alloy acetabular cup. Over 200,000 Metasul combinations have
been implanted to date. Short-term clinical performance has been encouraging; with low wear
rates, and few prostheses requiring revision. However, long-term clinical performance is as
yet unknown.
Although MOM hip prostheses produce significantly lower wear rates than conventional
UHMWPE-on-metal couples, and lower wear rates than highly crosslinked UHMWPE-on-metal hip
prostheses, there are concerns associated with these bearings. Wear particles have been
reported to be in the nanometer size range, an order of magnitude smaller than UHMWPE
particles. Therefore, despite a lower wear volume than UHMWPE bearings the number of
particles produced are estimated to be greater, possibly between one and ten million
particles per step. These small particles have the potential to distribute throughout the
body via the lymphatic system, with particles found in the lymph nodes, liver, spleen and
bone marrow. As MOM hip prostheses are indicated for younger more active patients these
particles will be present at these sites for a long period of time, possibly 30-40 years.
Concern has been expressed about the biological response to metal particles released from
metal-on-metal couplings. The levels of cobalt and chromium ions have been measured in the
blood and serum in patients with successful THR, but information about the possible release
of aluminum from ceramic-on-ceramic articulations is lacking.
A better understanding of the influence of the metallurgy and tribology on wear of the
component and improved manufacturing technology have allowed the re-introduction of
metal-on-metal articulations in total hip replacement. Excellent early clinical outcome has
been reported with the new generation of metal-on-metal components. Retrieval studies of
previous metal-on-metal bearings and contemporary implants have shown low rate of wear.
These hard bearing surfaces are especially promising for young and active patients. Although
metal-on-metal bearings produce significantly less wear debris than metal-on-polyethylene
bearing surfaces, the debris generated results in the body being exposed to metal ions for
prolonged periods. Concerns exist over metal hypersensitivity, osteolysis, chromosomal
mutation, carcinogenicity and fetal exposure to high ion levels. These matters require
further investigation, particularly the long-term exposure in younger patients and the
recognition that some patients may have unusually high ion levels. From tribological
studies, joint simulation testing and clinical trials, it has been proposed that the extent
of wear can be reduced by using components with a larger diameter with a high carbon content
in the alloy (0.2%), well-adjusted clearance for the components, better implant sphericity
and lower surface roughness.
Whilst research has shown that high concentrations of nanometre-sized metal wear particles
are cytotoxic to human fibroblasts and macrophages in vitro, there are also concerns about
the release of metal ions from these small particles, and the potential effect that these
ions have on cells and tissues. Elevated ion concentrations have been reported in both the
blood and urine of patients with metallic implant components. In addition, contrary to what
might be expected, there is no conclusive evidence that ion levels fall in vivo after the
bedding in period of the MOM prostheses, during which wear of the prostheses are higher.
Cobalt and chromium ions have high toxicity, and there are very real concerns about the
effects of sub-lethal doses of metal ions, which have been shown to cause DNA damage. This
damage takes the form of chromosome aberrations and chromosome translocations. Over long
periods of exposure the worry is that this will lead to the development of certain types of
cancer, such as leukaemia and lymphoma. In animal models elevated levels of cobalt, chromium
and nickel have been correlated with increased carcinoma rates. However, reports in the
literature of malignancies developing after total hip or knee replacement surgery are
exceedingly rare. Out of eight epidemiological studies on the relative risk of cancer after
TJR, only one study looked specifically at MOM implants. This study did not find an
increased risk of cancer development in the subjects receiving MOM hip prostheses compared
to those receiving metal-on-polyethylene hip prostheses. However, all the studies to date
have been substantially underpowered in terms of patient numbers required to show a
difference between the two prosthesis types.
High levels of cobalt and chromium ions are detected in the blood and urine of patients with
metal-on-metal (MOM) hip replacement despite, even with these elements are released as a
result of wear at the bearing surfaces. The clinical effects of elevated metal ion levels
include local tissue reactions, characterized by increases in T and B cells in the tissues
surrounding the hip, and are associated with premature failure of the hip. Systemically, one
report suggests reduced numbers of CD8-positive T cells. Metal sensitivity is also a
potential problem. Metal ions, whether produced secondary to wear debris or via corrosion
can initiate a hypersensitivity response. A delayed cell-mediated response, or delayed-type
hypersensitivity response can occur, in which cytokines are released by T-lymphocytes and
increased activation of macrophages is seen, which may result in T-cell mediated
periprosthetic osteolysis. Many metals can initiate a hypersensitivity response, the most
common is nickel followed by cobalt and chromium. Therefore, with the well-documented
elevation of cobalt and chromium ions in patients with MOM hip implants, there is a
theoretical risk of developing hypersensitivity reactions. Recently, an immune response
exclusively associated with second-generation MOM hip prostheses, has been described.
Histomorphological changes suggest a type of hypersensitivity reaction to the all-metallic
implants. The hypersensitivity hypothesis was further strengthened by the observation that
these patients experienced early clinical failure at 11-60 months (mean 29 months), and the
fact that patients who received a second MOM prosthesis did not experience any relief of
symptoms. Conversely, patients who received either metal-on-polyethylene or
ceramic-on-polyethylene couples reported that their symptoms completely disappeared. In a
control group of patients with joint prostheses not containing cobalt, chromium or nickel
these signs of an immunological reactions were absent. Reports of this type of reaction are
becoming increasingly common; however, more research is needed in this area. It is not known
whether these patients experience prosthesis failure because of a pre-existing metal
sensitivity, or whether metal sensitivity develops because of a high wearing bearing and
elevated metal ion levels. Theoretically, there would be an increased probability of
developing hypersensitivity to elevated metal ion levels, and hence an increased risk of
implant failure.
To reduce the effect of these limitations, such as the breakage of the ceramic insert in COM
bearing and to reduce ions release in MOM bearing a hybrid coupling of ceramic-on-metal has
been proposed. The theoretical advantage of this new coupling might lead orthopedic surgeons
to use it indiscriminately.
