Clinical trial NCT03293147: OUTREACH: Urine Analysis and Antihypertensive Treatment
Official title: BiOmarkers in Urine, anTihypeRtensive trEAtment and Blood Pressure Control in Hypertensive Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Adherence, Medication
Keywords: Blood pressure
Antihypertensive treatment
Adherence
Biomarker
Urine
HPLC-MS/MS
Lead sponsor: University of Manchester
Sponsor class: OTHER
Collaborators: name: British Heart Foundation
name: Manchester Academic Health Science Centre
name: Omron Healthcare Co., Ltd.
First posted: 2017-09-26
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center randomised controlled trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: Change in Clinic systolic blood pressure
timeFrame: visit 4 (short term follow-up; approx. 3 months post intervention, when feasible to conduct)
Secondary outcomes:
measure: Change in clinic systolic blood pressure
timeFrame: visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
measure: Change in clinic diastolic blood pressure
timeFrame: visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
measure: Change in clinic diastolic blood pressure
timeFrame: visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
measure: Change in home blood pressure
timeFrame: visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
measure: Change in home blood pressure
timeFrame: visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
measure: Change in biochemical adherence of patients
timeFrame: visit 2 (~3 weeks post recruitment, when feasible to conduct)
measure: Change in biochemical adherence of patients
timeFrame: visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
measure: Change in biochemical adherence of patients
timeFrame: visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
measure: Change in urinary albumin / creatinine ratio
timeFrame: visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
measure: Change in urinary albumin / creatinine ratio
timeFrame: visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
measure: Changes in health economy parameters
timeFrame: visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
measure: Changes in health economy parameters
timeFrame: visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
Other outcomes:
measure: Changes in psychological profile
timeFrame: visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
measure: Changes in psychological profile
timeFrame: visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
Locations:
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
state: Greater London
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
state: Greater Manchester
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Derby
country: United Kingdom
facility: Alvaston Medical Centre
city: Epsom
country: United Kingdom
facility: Epsom & St. Helier University Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: Glenfield General Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital
city: London
country: United Kingdom
facility: Homerton Hospital
city: London
country: United Kingdom
facility: St Bartholomews Hospital
city: Nottingham
country: United Kingdom
facility: Chilwell Valley and Meadows Practice
city: Poole
country: United Kingdom
facility: University Hospitals Dorset NHS Foundation Trust
Study officials:
affiliation: University of Manchester
name: Maciej Tomaszewski, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References: