Clinical trial NCT02331264: Cardiac Assessment of Patients With Hip Implants
Official title: Cardiac Assessment of Patients With Hip Implants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiomyopathy
Cardiac Failure
Keywords: Cardiac Toxicity
Metal on Metal Hip Implants
Lead sponsor: Royal National Orthopaedic Hospital NHS Trust
Sponsor class: OTHER
Collaborators: name: University College London Hospitals
First posted: 2015-01-06
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with hip replacements. Groups 1 and 2 include patients with Metal on Metal hip replacements. Group 3 includes patients with non Metal bearing hip replacements including Ceramic on Ceramic Hip replacements.

All three groups will be matched for Age, Sex, Time since hip Implantation, and diabetes status.

Brief summary: PRIMARY OBJECTIVE To establish the effect of metal ion release from metal hip implants on cardiac function

STUDY OUTCOME MEASURES

To assess the effect of metal ions from hip implants on cardiac function as measured by Cardiac Magnetic Resonance Imaging (CMR) and Echocardiogram. This involves the surrogate detection of cobalt ion deposition within cardiac tissues and assessment of ejection fraction and tissue characterization (with and without contrast).

STUDY IMPACT

With 60,000 patients having a metal on metal (MOM) hip implant in the United Kingdom (UK), and over a million worldwide, there is need to clarify this important question, which is the source of significant concern amongst patients and surgeons alike. Also, this problem is not unique to MOM hips since all hip implants contain metal and as seen in various case reports high blood cobalt levels have arisen after catastrophic failure (e.g. fracture of a ceramic bearing surface) leading to abnormal wear of the implant and release of metal ions into the body. In the UK, over 80,000 hip implants are inserted annually.

Detailed description: BACKGROUND

Metal-on-metal (MOM) hip implants have a risk of releasing metal ions upon wear of the component material. Some of the metal ions (e.g. cobalt and chromium) from the metal implant or from the metal particles will enter the bloodstream.

The Food and Drug Administration (FDA, USA) recently highlighted systemic toxicity from metal on metal hip implants as a cause for concern and recommended that patients with systemic symptoms are assessed with a particular focus on cardiovascular, neurological, endocrinological (especially thyroid), and renal systems.

A number of cases of suspected toxicity to circulating cobalt and chromium from MOM hip implants, including cardiac toxicity, have been reported recently. The most profound case involves a patient who died from cardiac failure secondary to cardiomyopathy and cobalt deposition within the cardiac tissues. A recent cross sectional health screen and isolated case reports, suggest that raised metal ion levels have the potential to cause cardiomyopathy and cardiac failure. Such cases have raised public anxiety in the process.

Blood metal ions released from metal hip implants are increasingly recognized as a potential cause of local and distant abnormal tissue responses, since cobalt and chromium is released into the peri-prosthetic tissues and transported systemically throughout the body. Component design and positioning are associated with increased wear and as a result raised metal ion levels. However, a definitive causal link to systemic symptoms still remains to be established.

Iron overload disorders affecting the heart or liver is a significant cause of morbidity in primary and secondary haemochromatosis and thalassaemia. Excessive iron deposition within cardiac tissues can lead to premature death secondary to fatal arrhythmias and heart failure. Cardiovascular magnetic resonance (CMR) imaging has revolutionised the management of this particular group of patients by allowing a robust non-invasive method of detecting iron loading.

CMR is the gold-standard method of assessing cardiac volumes, function and mass. It's unique strength over other imaging modalities is tissue characterization with and without the use of contrast agents. Myocardial iron is detected due to the effects on relaxation times through the interaction of iron with hydrogen nuclei in normal cardiac tissue. Cobalt is a ferromagnetic metal containing unpaired electrons allowing it to align in parallel to applied magnetic fields, and therefore should be detected by MRI in a similar way to iron.

RATIONALE

No study has attempted to identify cobalt deposition within cardiac tissue using cardiac MRI. We therefore aim to detect cobalt deposition in the cardiac tissue of patients with metal hip implants and markedly raised cobalt blood ion levels. If detected, we aim to assess whether this had any clinical effect on cardiac function.

Our hypothesis is that there is no discernable effect on cardiac function detectable on Cardiac MRI and Echocardiography in patients with raised blood cobalt ion levels.

Case Controlled Cohort Observation study

Three groups of patients will be identified with Hip implants (matched for age, sex and time since surgery).

1. Patients with MOM hip implant and raised metal ion level (\>7ppb) - N=30
2. Patients with MOM hip implant and Normal Metal ion level (\<7ppb) - N=30
3. Patients with non-metal bearing hip implant (Ceramic on Ceramic/Polyethylene (COC/COP)) - N=30

Selection into each group will be defined by metal ion blood tests and hip implant type. Patients with two consecutive blood tests at the appropriate level and less than 10% variation (in the last 12 months) will be included, or those with a blood test at the appropriate level taken in the last 3 months will be included.

The cardiologist will be blinded with regards to patient grouping, to ensure there is no bias when reporting the clinical and cardiological investigations results in light of the presence or absence of raised blood metal ions.

All participants enrolled will:

* Be assessed by a cardiologist
* Have a cardiac MRI, an ECHOcardiogram, and an Electrocardiogram (ECG)

These clinical data will be analysed and compared to assess if a significant difference exists between the 3 groups.

Eligibility criteria: Inclusion Criteria:

1. Age over 18 years of age
2. Either male or female
3. Metal on Metal hip implant (ceramic on ceramic hip implant for patients within control group)
4. Implanted greater than 12 months (i.e. beyond the bedding in period of the implant)
5. Suitable for MRI scanning (no contraindications for Magnetic scanning - for instance metal implants in eyes/brain/heart, and claustrophobia)
6. Consenting to the proposed research activity

Exclusion Criteria:

1. Age below 18 years
2. Metal hip implant not considered as MOM or Ceramic on Ceramic (COC) if part of the control group
3. Not suitable to undergo MRI scanning (contra-indications or claustrophobia)
4. Revised hip implant
5. Atrial Fibrillation
6. Poor renal function (eGFR\<30)
7. Consent not given
8. Vulnerable adults

Primary outcomes:
measure: Cardiac Ejection Fraction
timeFrame: 1 hour
Secondary outcomes:
measure: Detection of Cobalt Metal Ion deposition within cardiac tissues
timeFrame: 30 mins
Other outcomes:
Locations:
city: Stanmore
country: United Kingdom
facility: Royal National Orthopaedic Hospital
state: London
city: London
country: United Kingdom
facility: The Heart Hospital
Study officials:
affiliation: Professor of Orthopaedic Surgery at UCL and Consultant Orthopaedic Surgeon at the RNOH. Director of research and development at the RNOH.
name: Alister Hart, MD,FRCSG
role: PRINCIPAL_INVESTIGATOR
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