Personalised approach to hypertension treatment: Rationale and design of the HYPERMARKER randomised trial

Background and ObjectiveBlood pressure treatment response is variable in individual patients, and the choice of medical therapy is often dependent on clinician experience. Treatment choices can be personalised by patient empowerment, metabolomic profiles and augmented by machine learning, but robust evaluation is lacking on how these can be combined to enhance clinical effectiveness. The HYPERMARKER trial will evaluate how an individualised choice of medication class can address the avoidable global health and economic burdens of hypertension. Design and InterventionThe HYPERMARKER trial is a proof-of-concept, pragmatic, multicentre, adaptive, open-label strategy trial embedded into routine clinical practice with stratified individual patient randomisation. The trial was co-designed with a patient and public involvement team. The intervention is a digital portal that supports shared decision making on hypertension therapy class using clinical features plus metabolomic profiles determined with liquid chromatography-mass spectrometry. Participants and OutcomesEligible patients are aged [≥]18yrs with a systolic blood pressure [≥]140mmHg and a clinical indication for antihypertensive therapy. 400 participants will be randomised to usual standard of care for treatment selection, or to the intervention group. Remote follow-up will occur through a patient smartphone application and linked blood pressure monitor to assess the primary outcome of change in home systolic blood pressure during a four-week period after medication changes. Secondary outcomes will include patient-reported adverse effects and quality of life, treatment withdrawal, healthcare utilisation and a health economic analysis. In the second phase of the trial, all participants will receive an updated version of the intervention, regardless of original randomised group. Ethics and DisseminationEthical approval will be obtained for all sites. Approval in England: North West - Greater Manchester West Research Ethics Committee (REC) (25/NW/0296). Trial results will be disseminated via peer-reviewed publications and plain language patient summaries. Trial registrationClinicaltrials.gov: NCT07294794; ISRCTN: ISRCTN29385951. STRENGTH AND LIMITATIONS OF THIS STUDYO_LIHypertension is a major cause of preventable morbidity and mortality, and this study aims to reduce those burdens through machine learning-based integration of metabolomics with clinical factors to enable better personalisation of blood pressure lowering therapy. C_LIO_LIThe HYPERMARKER trial was co-created with patient and public representatives, using digital technology with remote monitoring to facilitate a high level of shared care and patient empowerment. C_LIO_LIHYPERMARKER is a pragmatic proof-of-concept randomised trial designed to evaluate the potential for future pharmacometabolomic strategies to aid clinical decision-making. C_LI