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OUTREACH: Urine Analysis and Antihypertensive Treatment

Not Applicable
Completed
Conditions
Hypertension
Adherence, Medication
Interventions
Other: Standard care
Other: HPLC-MS/MS-guided intervention
Registration Number
NCT03293147
Lead Sponsor
University of Manchester
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
200
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm CStandard careControl group: Adherent hypertensive patients randomised in Arm C will receive clinical standard care.
Arm AHPLC-MS/MS-guided interventionIntervention group: Non-adherent hypertensive patients randomised in Arm A will receive standard clinical care plus HPLC-MS/MS-guided intervention.
Arm BStandard careControl group: Non-adherent hypertensive patients randomised in Arm B will receive clinical standard care.
Primary Outcome Measures
NameTimeMethod
Change in Clinic systolic blood pressurevisit 4 (short term follow-up; approx. 3 months post intervention, when feasible to conduct)

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

Secondary Outcome Measures
NameTimeMethod
Change in urinary albumin / creatinine ratiovisit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

Urinary albumin / creatinine ratio is a urinary marker of target organ damage.

Change in clinic diastolic blood pressurevisit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

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

Change in biochemical adherence of patientsvisit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

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.

Change in clinic systolic blood pressurevisit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

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

Changes in health economy parametersvisit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

Health economy parameters (collected via questionnaires) will be calculated over the study time horizon to determine total costs of clinical/social care

Change in home blood pressurevisit 5 (long term follow-up; ~4.5 months post intervention, when feasible to conduct)

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).

Trial Locations

Locations (12)

University College London Hospitals NHS Foundation Trust

🇬🇧

London, Greater London, United Kingdom

Ninewells Hospital

🇬🇧

Dundee, Scotland, United Kingdom

Manchester Royal Infirmary

🇬🇧

Manchester, Greater Manchester, United Kingdom

Glenfield General Hospital

🇬🇧

Leicester, United Kingdom

Alvaston Medical Centre

🇬🇧

Derby, United Kingdom

Epsom & St. Helier University Hospitals NHS Trust

🇬🇧

Epsom, United Kingdom

Guy's and St Thomas' Hospital

🇬🇧

London, United Kingdom

Royal Free Hospital

🇬🇧

London, United Kingdom

Homerton Hospital

🇬🇧

London, United Kingdom

St Bartholomews Hospital

🇬🇧

London, United Kingdom

University Hospitals Dorset NHS Foundation Trust

🇬🇧

Poole, United Kingdom

Chilwell Valley and Meadows Practice

🇬🇧

Nottingham, United Kingdom

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