A Prospective Observational Study to Assess the Impact of Pharmacogenetics on Outcomes in Vascular Surgery (PROSPER)

Introduction Patients with chronic limb threatening ischaemia (CLTI) are often prescribed clopidogrel in order to reduce their risk of major adverse limb and cardiovascular events. Clopidogrel is metabolised by the CYP2C19 enzyme, and genetics variations in CYP2C19 are common. These variants can influence an individual’s ability to metabolise clopidogrel to its active metabolite. This work aims to establish the relationship between patient genotype and outcomes after revascularisation in patients with CLTI who are prescribed clopidogrel. It will consider whether pharmacogenetics can be used to ensure patients are prescribed effective medications to optimise their outcomes. Methods and analysis This is a prospective observational cross-sectional study of patients undergoing lower limb surgical, endovascular or hybrid revascularisation for CLTI. Patients taking clopidogrel post-procedure, as well as those prescribed a non-clopidogrel based medication regimen, will be recruited prior to or shortly after revascularisation. Patients will undergo CYP2C19 genotyping and will be followed-up using online records. Ethics and dissemination Manchester University Research Ethics Committee approval as obtained was part of the Implementing Pharmacogenetics to Improve Prescribing (IPTIP) trial process (IRAS 305751). The results of the study will be published in a peer-review journal and presented at international conferences. Registration This work is a sub-protocol for the IPTIP study which is registered as [ISRCTN14050335][1]. ### Competing Interest Statement Competing interests John McDermott and William Newman are co-founders of Fava Health. The other authors have no competing interests. ### Funding Statement Funding Kerry Burke, John McDermott (JHM), William Newman (WGN) and Stuart Wright (SJW) receive grant support from the NHSE Network of Excellence in Pharmacogenetics. JHM and WGN receive grant funding from the BBSRC (BB/X003442/1), Manchester NIHR HealthTech Research Centre, Manchester NIHR BRC (NIHR203308) and Innovate UK (10058536) JHM is funded by National Institute for Health and Care Research (NIHR) Doctoral Fellowship Award (NIHR 301748). SJW is supported by a Wellcome Trust Early-Career Award (226922/Z/23/Z). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Manchester University Research Ethics Committee gave ethical approval for this work as part of the Implementing Pharmacogenetics to Improve Prescribing (IPTIP) trial process (IRAS 305751). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes An anonymised version of the genetic dataset will be stored in a data repository with no limitations on access or use. Genotype data will be deposited in the Figshare repository () at the end of the study following publication. Data will be open access and will be entirely anonymised, with no study ID. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN14050335