NCT02847338

Comparison of Optimal Hypertension Regimens

Comparison of Optimal Hypertension Regimens (Part of the Ancestry Informative Markers in Hypertension (AIMHY) Programme - AIMHY-INFORM)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 940 (actual)
• Sponsor: Cambridge University Hospitals NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

High blood pressure (Hypertension) is extremely common and is a major cause of heart disease, kidney disease and stroke. One in three of the UK (United Kingdom) population will require treatment for hypertension at some point in their lives. A healthy lifestyle alone is often not enough to control blood pressure, and drug treatment is usually required. Although a wide variety of drugs are available to treat hypertension, choosing the right kind of tablet or combination of tablets for individual patients is a problem, and therefore many people have poor blood pressure control. Hypertension treatment within the UK is currently selected according to age and self-defined ethnicity (SDE). There are limitations to this approach which include wide variability in the response to hypertension drug classes between people. There is also uncertainty about selecting hypertension drugs for ethnic minorities other than those of African/Caribbean ancestry, for example, South Asians because of a lack of information from trials. In the AIM HY-INFORM study the investigators are looking to recruit equal number of black/caribbean, south asian and white european participants to be able to compare differences in hypertension treatments and ethnicity. The primary objective of this study is to determine if the response to antihypertensive drugs differs by self defined ethnicity.

Detailed description

In the UK, current NICE (National Institute for Health and Clinical Excellence) guidance stratifies hypertension treatment according to age and self-defined ethnicity (SDE). Different initial monotherapies are recommended for all those aged over 55 years, and for younger black compared to white individuals. However, there is no recommended stratification for combination therapy. The evidence based supporting the current guidance on SDE stratification is limited, and there is a specific lack of data from UK based populations. Stratification based on SDE has a number of limitations and an alternative approach is stratification based on ancestry informative markers (AIM). There are genetic polymorphisms, which show substantially different frequencies between populations from different geographical regions, and can predict geographical ancestry with remarkable accuracy. AIM are thus more likely to capture the genetic component of variation in drug response in ethnically diverse population. Metabolomic profiling of plasma and urine may provide complementary information to AIM, as differences between individuals will reflect both genetic and environmental influences. To address these issues the investigators intend to compare the variation in response to antihypertensive drug treatments in three SDE cohorts, and relate this to variation in AIM and metabolomic profiles. Our objective is to test the validity of current NICE guidance on antihypertensives stratification based on SDE, to provide evidence about SDE stratification for dual therapy, and to examine whether more effective personalisation of antihypertensive treatment, can be achieved using AIM and/or metabolomic profiling. An assessment of patient stratification based on AIM phenotypes against SDE will enable the selection of optimal and more effective choices of anti-hypertensive treatments from currently existing first line drugs (and combinations of) and ultimately reduce the attrition of antihypertensive therapies. Output from the trial will provide the first perspective evidence for best treatment choice according to SDE for white, black and asian populations in the UK. This should reduce the number of consultations; time required to achieve optimal blood pressure control and the contribution to between hypertension control in the UK. Patients in the trial will be enrolled on a monotherapy or dual therapy regime depending on their history of hypertension. The monotherapy group of patients will enter a randomised, open-label, three-treatment three-period cross over trial. The dual therapy group of patients will enter a randomised, open-label, four-treatment four-period cross over trial. Randomisation, for each crossover design, will be stratified by three SDE groups. The duration for individual participants will be approximately 24 (monotherapy) or 32 weeks (dual therapy) The hypertensive medication used in this trial are: Amlodipine 5 or 10mg, Chlortalidone 25mg, Amiloride 10mg, Lisinopril 10 or 20mg, Participants on the dual therapy treatment arm will have a total of 11 visits including screening/enrolment (visit 1) and baseline visit (visit 2) Participants on the monotherapy treatment arm will have a total of 9 visits including screening/enrolment (visit 1) and baseline visit (visit 2) A total number of 1320 participants will be enrolled in the study across participating sites, so that approximately 660 participants in each therapy regime (approximately 220 participants per ethnic group) complete the trial. An optional skin-sodium investigation will be conducted at selected sites only where capacity and capability to complete the sub study investigations is demonstrated. The sub study aims to recruit up to 60 participants who have already given consent for the main AIM HY INFORM Trial. Consent for the optional sub-study will be obtained separately. The investigation comprises two optional assessments: a skin biopsy and a sodium magnetic resonance imaging (23Na MRI) scan. Both assessments will be used to quantify skin sodium levels. Participants in the mono and dual therapy arms can elect to have the skin biopsy, the MRI scan, or both, at the baseline visit. Participants in the mono therapy arm only, can elect to have the skin biopsy, the MRI scan, or both, following completion of the amlodipine (A) and chlortalidone (C) study arms. The additional measurements are not anticipated to take more than approximately 2 hours.

Conditions

• Hypertension

Interventions

Type	Name	Description
DRUG	Amlodipine	Amlodipine 5mg and Amlodipine 10mg will be one of the treatments in which patients will receive on the monotherapy arm and on the dual therapy arm.
DRUG	Lisinopril	Lisinopril 10mg and Lisinopril 20mg will be one of the treatments in which patients will receive on the monotherapy arm. Lisinopril 20mg will be one of the treatments in which patients will receive on the dual therapy arm.
DRUG	Amiloride	Amiloride 10mg will be one of the treatments in which patients will receive on the dual therapy arm.
DRUG	Chlortalidone	Chlortalidone 25mg will be one of the treatments in which patients will receive on the dual therapy arm and monotherapy arm.

Timeline

• Start date: 2016-11-01
• Primary completion: 2023-10-01
• Completion: 2023-10-01
• First posted: 2016-07-28
• Last updated: 2025-09-05

Locations

14 sites across 1 country: United Kingdom