OUTREACH: Urine Analysis and Antihypertensive Treatment (OUTREACH)

BiOmarkers in Urine, anTihypeRtensive trEAtment and Blood Pressure Control in Hypertensive Patients

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Adherence, Medication
• Intervention / Treatment: Other: HPLC-MS/MS-guided intervention; Other: Standard care

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marta Ahmed, MA; Phone Number: 51227 +44 (0)161 276 1227; Email: OUTREACH1@manchester.ac.uk

Study Locations

• United Kingdom
  • Derby, United Kingdom, DE24 0GE
    • Alvaston Medical Centre
  • Epsom, United Kingdom, KT17 1HB
    • Epsom & St. Helier University Hospitals NHS Trust
  • Leicester, United Kingdom, LE3 9QP
    • Glenfield General Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' Hospital
  • London, United Kingdom
    • Homerton Hospital
  • London, United Kingdom
    • St Bartholomews Hospital
  • Nottingham, United Kingdom, NG9 6DX
    • Chilwell Valley and Meadows Practice
  • Poole, United Kingdom, BH15 2JB
    • University Hospitals Dorset NHS Foundation Trust
  • Greater London
    • London, Greater London, United Kingdom
      • University College London Hospitals NHS Foundation Trust
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Manchester Royal Infirmary
  • Scotland
    • Dundee, Scotland, United Kingdom, DD2 1SY
      • Ninewells Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Intervention group: Non-adherent hypertensive patients randomised in Arm A will receive standard clinical care plus HPLC-MS/MS-guided intervention.	Other: HPLC-MS/MS-guided intervention; The HPLC-MS/MS-guided intervention consists of providing partially or totally non-adherent hypertensive patients with information on the results of their HPLC-MS/MS-based urine analysis combined with tailored targeting of the main reason(s) for the deviation from the prescribed antihypertensive treatment
Active Comparator: Arm B; Control group: Non-adherent hypertensive patients randomised in Arm B will receive clinical standard care.	Other: Standard care; Standard care for hypertensive patients
Active Comparator: Arm C; Control group: Adherent hypertensive patients randomised in Arm C will receive clinical standard care.	Other: Standard care; Standard care for hypertensive patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinic systolic blood pressure	Blood pressure measurements will be taken after 5 minutes of rest in a sitting position with an electronic digital Omron monitor and the cuff size adjusted to the arm circumference as per international guidelines. Three measurements of systolic blood pressure will be taken in a row (separated by approximately 1 minute interval) and recorded at every visit	visit 4 (short term follow-up; approx. 3 months post intervention, when feasible to conduct)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in clinic systolic blood pressure	Blood pressure measurements will be taken after 5 minutes of rest in a sitting position with an electronic digital Omron monitor and the cuff size adjusted to the arm circumference as per international guidelines. Three measurements of systolic blood pressure will be taken in a row (separated by approximately 1 minute interval) and recorded at every visit	visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
Change in clinic diastolic blood pressure	Blood pressure measurements will be taken after 5 minutes of rest in a sitting position with an electronic digital Omron monitor and the cuff size adjusted to the arm circumference as per international guidelines. Three measurements of diastolic blood pressure will be taken in a row (separated by approximately 1 minute interval) and recorded at every visit	visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
Change in clinic diastolic blood pressure	Blood pressure measurements will be taken after 5 minutes of rest in a sitting position with an electronic digital Omron monitor and the cuff size adjusted to the arm circumference as per international guidelines. Three measurements of diastolic blood pressure will be taken in a row (separated by approximately 1 minute interval) and recorded at every visit	visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
Change in home blood pressure	This measurement will be conducted using oscillometric Omron monitors. Patients will be handed the monitors by the research nurses at each visit and will be provided instructions to use the Omron monitor. While all blood pressure measurements will be stored automatically on the monitors, patients will be also asked to keep a written record on paper (to avoid loss of data in case a monitor stops working or goes out of order).	visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
Change in home blood pressure	This measurement will be conducted using oscillometric Omron monitors. Patients will be handed the monitors by the research nurses at each visit and will be provided instructions to use the Omron monitor. While all blood pressure measurements will be stored automatically on the monitors, patients will be also asked to keep a written record on paper (to avoid loss of data in case a monitor stops working or goes out of order).	visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
Change in biochemical adherence of patients	HPLC-MS/MS test will determine the numbers and list of antihypertensive drugs detected in the patient urine sample and this will be compared to the patient prescription	visit 2 (~3 weeks post recruitment, when feasible to conduct)
Change in biochemical adherence of patients	HPLC-MS/MS test will determine the numbers and list of antihypertensive drugs detected in the patient urine sample and this will be compared to the patient prescription.	visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
Change in biochemical adherence of patients	HPLC-MS/MS test will determine the numbers and list of antihypertensive drugs detected in the patient urine sample and this will be compared to the patient prescription.	visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
Change in urinary albumin / creatinine ratio	Urinary albumin / creatinine ratio is a urinary marker of target organ damage.	visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
Change in urinary albumin / creatinine ratio	Urinary albumin / creatinine ratio is a urinary marker of target organ damage.	visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)
Changes in health economy parameters	Health economy parameters (collected via questionnaires) will be calculated over the study time horizon to determine total costs of clinical/social care	visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
Changes in health economy parameters	Health economy parameters (collected via questionnaires) will be calculated over the study time horizon to determine total costs of clinical/social care	visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in psychological profile	Psychological questionnaires assessing participants perspectives of treatment will be completed by patient when attending clinic visit 1, 4 and 5	visit 4 (short term follow-up; ~3 months post intervention, when feasible to conduct)
Changes in psychological profile	Psychological questionnaires assessing participants perspectives of treatment will be completed by patient when attending clinic visit 1, 4 and 5	visit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

Collaborators and Investigators

• Sponsor: University of Manchester
• Collaborators: British Heart Foundation; Manchester Academic Health Science Centre; Omron Healthcare Co., Ltd.
• Investigators: Principal Investigator: Maciej Tomaszewski, Prof., MD, University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2018
• Primary Completion (Actual): August 4, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 21, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Adherence; Urine; Blood pressure; Antihypertensive treatment; HPLC-MS/MS
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: R120993

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No