OUTREACH: Urine Analysis and Antihypertensive Treatment

Sponsor

University of Manchester (Other)

Overall Status

Unknown status

CT.gov ID

NCT03293147

Collaborator

British Heart Foundation (Other), Manchester Academic Health Science Centre (Other), Omron Healthcare Co., Ltd. (Industry)

321

Enrollment

Locations

Arms

23.5

Anticipated Duration (Months)

45.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension Adherence, Medication	Other: HPLC-MS/MS-guided intervention Other: Standard care	N/A

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

321 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multi-center randomised controlled trialMulti-center randomised controlled trial

Masking:

Double (Participant, Investigator)

Masking Description:

Participants and clinicians will initially be blinded to the result of the baseline (at trial entry) HPLC-MS/MS based urine test to determine the participant adherence to antihypertensive treatment. Non-adherent patients allocated to Arm A will be un-blinded at the stage of visit 3 where the results of their HPLC-MS/MS urine test will be revealed to them as a part of HPLC-MS/MS-guided intervention. The doctor will also require un-blinding to provide the required intervention. However, during further study visits the research personnel will remain blinded as to the adherence status of these patients, the results of their HPLC-MS/MS-based analysis and the treatment allocation. The doctor who delivers the intervention will not be involved in collecting clinical information necessary to define outcomes during appointments 4 and 5. Hypertensive patients randomised to Arms B and C will remain blinded to the results of their HPLC-MS/MS-based urine test throughout all stages of the study.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 18, 2018

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in Clinic systolic blood pressure [visit 4 (short term follow-up; 3 months post intervention)]
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

Change in clinic systolic blood pressure [visit 5 (long term follow-up; ~11 months post intervention)]
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
Change in clinic diastolic blood pressure [visit 4 (short term follow-up; 3 months post intervention)]
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 clinic diastolic blood pressure [visit 5 (long term follow-up; ~11 months post intervention)]
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 home blood pressure [visit 4 (short term follow-up; 3 months post intervention)]
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).
Change in home blood pressure [visit 5 (long term follow-up; ~11 months post intervention)]
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).
Change in biochemical adherence of patients [visit 2 (two week post recruitment)]
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 biochemical adherence of patients [visit 4 (short term follow-up; 3 months post intervention)]
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 biochemical adherence of patients [visit 5 (long term follow-up; ~11 months post intervention)]
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 urinary albumin / creatinine ratio [visit 4 (short term follow-up; 3 months post intervention)]
Urinary albumin / creatinine ratio is a urinary marker of target organ damage.
Change in urinary albumin / creatinine ratio [visit 5 (long term follow-up; ~11 months post intervention)]
Urinary albumin / creatinine ratio is a urinary marker of target organ damage.
Changes in health economy parameters [visit 4 (short term follow-up; 3 months post intervention)]
Health economy parameters (collected via questionnaires) will be calculated over the study time horizon to determine total costs of clinical/social care
Changes in health economy parameters [visit 5 (long term follow-up; ~11 months post intervention)]
Health economy parameters (collected via questionnaires) will be calculated over the study time horizon to determine total costs of clinical/social care

Other Outcome Measures

Changes in psychological profile [visit 4 (short term follow-up; 3 months post intervention)]
Psychological questionnaires assessing participants perspectives of treatment will be completed by patient when attending clinic visit 1, 4 and 5
Changes in psychological profile [visit 5 (long term follow-up; ~11 months post intervention)]
Psychological questionnaires assessing participants perspectives of treatment will be completed by patient when attending clinic visit 1, 4 and 5

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 willing and able to give informed consent for study inclusion including all study assessments

Exclusion Criteria:

Patients with recent history of admission to the hospital within 2 weeks of baseline visit (i)
Patients with recent changes in the prescribed antihypertensive medications within 2 weeks of baseline visit (ii)
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 12 months

(i) Including admission to A&E (ii) Changes in antihypertensive drug dose are not considered an exclusion criteria if this is the only change within 2 weeks of the baseline visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Manchester Royal Infirmary	Manchester	Greater Manchester	United Kingdom	M13 9WL
2	Ninewells Hospital	Dundee	Scotland	United Kingdom	DD2 1SY
3	Epsom & St. Helier University Hospitals NHS Trust	Epsom		United Kingdom	KT17 1HB
4	Glenfield General Hospital	Leicester		United Kingdom	LE3 9QP
5	University College Hospital	London		United Kingdom	NW1 2BU
6	Guy's and St Thomas' Hospital	London		United Kingdom	SE1 7EH
7	King's College Hospital	London		United Kingdom	SE5 9RS