OUTREACH: Urine Analysis and Antihypertensive Treatment

Hypertension Clinical Trial

— OUTREACH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03293147
• Other study ID #: R120993
• Status: Completed
• Phase: N/A
• Start date: December 18, 2018
• Est. completion date: September 30, 2023

Study information

• Verified date: January 2024
• Source: University of Manchester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: September 30, 2023
• Est. primary completion date: August 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adherence, Medication
• Hypertension

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
• Standard care
Standard care for hypertensive patients

Locations

Country	Name	City	State
United Kingdom	Alvaston Medical Centre	Derby
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Epsom & St. Helier University Hospitals NHS Trust	Epsom
United Kingdom	Glenfield General Hospital	Leicester
United Kingdom	Guy's and St Thomas' Hospital	London
United Kingdom	Homerton Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	St Bartholomews Hospital	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London	Greater London
United Kingdom	Manchester Royal Infirmary	Manchester	Greater Manchester
United Kingdom	Chilwell Valley and Meadows Practice	Nottingham
United Kingdom	University Hospitals Dorset NHS Foundation Trust	Poole

Sponsors (4)

Lead Sponsor	Collaborator
University of Manchester	British Heart Foundation, Manchester Academic Health Science Centre, Omron Healthcare Co., Ltd.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)