OUTREACH: Urine Analysis and Antihypertensive Treatment

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hypertension, Adherence, Medication

Intervention / Treatment
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* Other: HPLC-MS/MS-guided intervention
* Other: Standard care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-center randomised controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>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<br>* 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<br>|
| Active Comparator: Arm B<br>Control group: Non-adherent hypertensive patients randomised in Arm B will receive clinical standard care. | Other: Standard care<br>* Standard care for hypertensive patients<br>|
| Active Comparator: Arm C<br>Control group: Adherent hypertensive patients randomised in Arm C will receive clinical standard care. | Other: Standard care<br>* Standard care for hypertensive patients<br>|

What is the study measuring?
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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; 3 months post intervention) | 

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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, Antihypertensive treatment, Adherence, Biomarker, Urine, HPLC-MS/MS