OUTREACH: Urine Analysis and Antihypertensive Treatment

Non-adherence to antihypertensive treatment is one of the leading causes of suboptimal blood pressure control and translates into increased risk of cardiovascular morbidity and mortality. Currently, there is no effective intervention for therapeutic non-adherence. Our project will assess whether high performance liquid chromatography mass spectrometry (HPLC-MS/MS)-guided intervention (providing patients with information on the results of their HPLC-MS/MS-based urine analysis combined with targeting the main reason for non-adherence) leads to an improvement in blood pressure control, adherence and a reduction in healthcare costs. Our multicentre prospective randomised controlled trial consists of 6 stages (screening, recruitment, baseline phenotype assessment, intervention, short-term and long-term outcome visits). The study will fill in an important gap in knowledge on management of blood pressure in non-adherent hypertensive patients beyond the initial diagnostic step. It will also inform the development of a cost-effective model for the management of non-adherence in chronic disorders that require long-term drug therapy.

Non-adherence to antihypertensive treatment is one of the leading causes of suboptimal blood pressure control and translates into increased risk of cardiovascular morbidity and mortality. Currently, there is no effective intervention for therapeutic non-adherence.

An ultra-sensitive and highly specific biochemical assay has been developed to detect urinary biomarkers of antihypertensive treatment. The high performance liquid chromatography mass spectrometry (HPLC-MS/MS)-based assay screens spot urine samples for the presence of 40 commonly prescribed blood pressure lowering medications. The results of the test provide a clinician with information on the presence/absence of prescribed antihypertensive drugs or/and their metabolites in urine - a direct confirmation of therapeutic adherence/non-adherence.

The study is a prospective multi-centre randomised controlled trial to examine if HPLC-MS/MS-guided intervention is superior to standard clinical care in improving clinical, behavioural and health-economy outcomes in hypertensive patients who are non-adherent to antihypertensive treatment.

Patient adherence to antihypertensive treatment will be determined at baseline. Non-adherent hypertensive patients at baseline will be randomised in a 1:1 ration to either usual clinical care plus HPLC-MS/MS-guided intervention (Arm A) or usual clinical care only (Arm B).

The study also evaluates a cohort of patients who are adherent to antihypertensive treatment at baseline. Those adherent hypertensive patients will receive the usual clinical care (Arm C). The main purpose of involving this group of patients is to blind the clinical research staff to the adherence status of those patients randomised receiving standard care alone, to prevent introducing any bias in treating non-adherent patients.

Eligibility Criteria:
Inclusion Criteria:

* Male or female aged 18 years or above
* Patients previously diagnosed with and pharmacologically managed for hypertension
* Patients with antihypertensive treatment with at least two antihypertensive medications
* Patients have full capability of providing informed consent

Exclusion Criteria:

* Patients with recent history of admission to the hospital relating to their hypertension or treatment with anti-hypertensive medications (\<2 weeks) (i)
* Patient refusal for 7-day home-based blood pressure monitoring (7-HBBPM)
* Self-reported pregnancy or breastfeeding
* Female patients planning to conceive within the next 6 months

  (i) Including admission to A\&E