A revolutionary point-of-care testing device that could help to prevent recurrent strokes could soon be rolled out across the NHS, according to researchers at the University of Manchester. The shoebox-sized device enables bedside testing using a cheek swab to detect genetic changes that reduce the effectiveness of clopidogrel, the current first line preventive treatment, so that alternative antiplatelet therapy can be prescribed.
Clopidogrel is metabolised to its active form by a protein encoded by the CYP2C19 gene. About 25% of patients in the UK – and up to 50% in different ethnic groups – carry variants that reduce their response to treatment, making them twice as likely to have further strokes if given clopidogrel as secondary prophylaxis.
Pre-treatment genotype testing to detect these variants enables alternative, more effective treatment to be prescribed for this group – which could be potentially lifesaving, they said.
Current Genetic Testing Expensive and Slow
Draft guidance from the National Institute for Health and Care Excellence (NICE) in May this year recommended CYP2C19 genetic testing prior to treatment after ischaemic stroke or transient ischaemic attack. Currently this usually involves expensive machines in specialist laboratories, and the process can take several weeks.
The manufacturers said that the new Genedrive CYP2C19 System is a point of care pharmacogenomic test that uses miniaturised technology to differentiate between patients likely to respond to clopidogrel and those who won't, allowing more effective, personalised treatment.
The test can be performed in the ward, or even at the bedside, with minimal training, and can deliver a "clinically actionable result" in about one hour. It has up to 99% accuracy in detecting the variants that underpin poor clopidogrel metabolism.
The device last week formally received a UK Conformity Assessed (UKCA) product mark, the UK’s equivalent of the European CE mark, which paves the way for its introduction across the NHS, its developers announced. The machine was developed by Manchester based company genedrive , working with a clinical team from the University of Manchester and Manchester University NHS Foundation Trust (MFT).
Point of Care Testing Allows Early Optimised Treatment
The company's CEO David Budd described UKCA marking as "a milestone". He pointed out that the risk of recurrent stroke is up to 10% in the first week, "so routine laboratory testing which can take many days or weeks is unlikely to be as appropriate as a point of care solution returning results in about one hour".
The test's performance will now be further evaluated in a clinical setting at Manchester Royal Infirmary and the Manchester Centre for Genomic Medicine, Saint Mary’s Hospital, both part of MFT, over the next six months.
Project leader Bill Newman, professor of translational genomic medicine at the University of Manchester, and consultant in genomic medicine at MFT, explained: "Patients who have had a stroke are likely to be at risk of further, more serious strokes. This is a worrying time for patients, their families and carers. Therefore, it is vital we use new approaches to ensure that patients get onto the right treatment as quickly as possible."
Pathway to Clinical Use
Researcher Dr John McDermott, a clinical geneticist at MFT and National Institute for Health and Care Research (NIHR) fellow at the University of Manchester, said: "A major challenge faced across healthcare is finding pathways develop, validate, and ultimately implement novel technology like this in the clinical setting."
The device prototype development was supported by a Wellcome Trust grant. In April this year the researchers were awarded £4.1million from Innovate UK to further develop time-critical genomic testing technology as part of the DEVOTE programme. This collaboration between industry, academics, and clinicians aims to support the development, validation, and implementation of novel healthcare technologies in the NHS.
According to NICE, the most common CYP2C19 loss of function allele, the *2 allele, is found in around 15% of people of European ethnicity, 18% of those of African-American or Caribbean heritage, and 27%-28% of people from an Asian background. The *3 allele is found in less than 1% of people from most populations, but 2% to 7% of Asians. Other variants are generally present in less than 1% of people.
However these numbers could be underestimates - a report last month showed that more than half of British Asians did not respond to clopidogrel.
Point of Care Test Could Detect More Variants Than Laboratory Testing
Asked to comment by Medscape News UK, Dr McDermott, who is also honorary clinical lecturer at the Manchester Centre for Genomic Medicine said: "The Genedrive system can detect the *2, *3, *4, *8, *17, and *35 alleles. This is more than most laboratories currently test for, with *2, *3 and *17 the most commonly genotyped alleles.
"The breadth of the Genedrive system means that the test can be deployed across multiple geographies and in people of different ethnic backgrounds, where rarer alleles are more common."
In terms of the test's likely progress towards NHS adoption, he said that upcoming final guidance from the NICE committee, due on 20 December, would be particularly important. "If this recommends all patients who have a TIA or ischaemic stroke should be offered CYP2C19 genotyping, then the Genedrive system is uniquely placed to deliver testing at the scale and speed which may be required."