Comparison of Optimal Hypertension Regimens

NCT02847338 | Completed Phase 4

• 1 other identifier: AO94005
• Study Type: interventional
• Target: 940
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Hypertension

Keywords

Hypertension

Outcome Measures

Primary Outcomes (1)

• Seated Automated Office Systolic Blood Pressure

  This is planned for all participants

  Approximately 8 weeks after receiving each treatment up to week 24 for mono therapy patients and up to week 32 for dual therapy patients

Secondary Outcomes (5)

• Seated Automatic office systolic blood pressure

  At every visit - every 4 weeks up to week 24 for mono therapy patients and every 4 weeks up to week 32 for dual therapy patients. From screening until last visit.

• Core Cardiovascular Measurements

  Core cardiovascular measurements will be performed on all participants at Baseline. For all patients there is an option for them to have the measurements repeated at weeks 8, 16, 24 Mono&Dual and week 32 Dual only, these subsequent visits are optional.

• Detailed Self Defined Ethnicity

  Screening visit only

• Ambulatory Blood Pressure and/or blood pressure

  This will be measured for a subgroup of patients at Baseline, week 8, week 16, week 24 Dual&Mono & week 32 Dual only

• Optional Cardiovascular measures

  These measurements will be performed on a subgroup of patients at Baseline, week 8, week 16, week 24 Dual&Mono & week 32 Dual only

Other Outcomes (2)

• Baseline demographic comparison

  Baseline visit

• Urine compliance drug screen

  These will be measured for a subgroup of patients at Baseline visit, week 8, week 16, week 24 Dual&Mono & week 32 Dual only

Study Arms (2)

Mono-therapy group

EXPERIMENTAL

The monotherapy group will be treated with the following treatments: A) 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg B) 1 to 2 weeks of Lisinopril 10mg followed by 6 to 7 weeks of Lisinopril 20mg C) Approximately 8 weeks of 25mg Chlortalidone Participants will be randomly allocated to one of six possible sequences of treatments of the three-treatment-three period Williams design: ABC, ACB, BAC, BCA, CAB, and CBA.

Drug: Amlodipine; Drug: Lisinopril; Drug: Chlortalidone

Dual-therapy arm

EXPERIMENTAL

The dual-therapy group will be treated with the following treatments: A) Approximately 8 weeks of Amlodipine 5mg and Lisinopril 20mg B) Approximately 8 weeks of Amlodipine 5mg and Chlortalidone 25mg C) Approximately 8 weeks of Lisinopril 20mg and Chlortalidone 25mg D) Approximately 8 weeks of Amiloride 10mg and Chlortalidone 25mg Participants will be randomly allocated to one of four possible sequences of treatments of the four-treatment four-period Williams design: ABDC, BCAD, CDBA, and DACB.

Drug: Amlodipine; Drug: Lisinopril; Drug: Amiloride; Drug: Chlortalidone

Interventions

Amlodipine DRUG

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.

Dual-therapy arm; Mono-therapy group

Lisinopril DRUG

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.

Dual-therapy arm; Mono-therapy group

Amiloride DRUG

Amiloride 10mg will be one of the treatments in which patients will receive on the dual therapy arm.

Dual-therapy arm

Chlortalidone DRUG

Chlortalidone 25mg will be one of the treatments in which patients will receive on the dual therapy arm and monotherapy arm.

Dual-therapy arm; Mono-therapy group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included in the trial the participant must:
• Have given written informed consent to participate
• Be aged 18 to 65 years inclusive
• Self-Define Ethnicity: participants should SELF IDENTIFY into 1 of the three groups below:
• White White British White Irish Any other white background
• Black or Black British Black Caribbean Black African Any other black background
• Asian or Asian British Asian Indian Asian Pakistani Asian Bangladeshi Any other Asian background
• Be hypertensive defined as:- Mono-therapy rotation
• currently untreated with EITHER an ABPM day time average blood pressure ≥ 135mmHG (systolic) or ≥ 85mmHg (diastolic) OR Home BP measurements using a validated device based on the average of 10 blood pressure readings of ≥135 mmHg (systolic) or ≥85 mmHg (diastolic)
• Patients who may be taking antihypertensive drugs at sub therapeutic doses or in ineffective combinations, and who are felt likely to be controllable on a study drug and willing and able to be washed out, at the discretion of the CI (Chief Investigator) / PI (Principal Investigator), can enter the trial if they meet the above criteria.
• Dual therapy rotation
• a.Treated hypertensive receiving one to three antihypertensive drugs with a blood pressure (ABPM daytime average blood pressure or Home BP as in a.) between 135 or 200 mmHg (systolic) AND between 85 or 110 mmHg (diastolic).

You may not qualify if:

• The presence of any of the following will mean participants are ineligible:
• Participant does not fit into one of the defined ethnic groups e.g. Mixed
• Pregnant or breastfeeding women
• Known or suspected secondary hypertension
• Significant sensitivity or contraindications to any of the study medications
• Participants taking lithium or are regularly consuming non-steroidal anti-inflammatory drugs at variable doses
• Requirement to take any of the study drugs continuously e.g. ACEi and heart failure
• Any clinically significant hepatic impairment
• Any clinically significant kidney impairment
• Patients who are deemed unsuitable by the investigator on clinical grounds

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• Medical Research Council: collaborator

Study Sites (14)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Sandwell & West Birmingham Hospitals NHS Trust

Birmingham, B18 7QH, United Kingdom

Location

Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

University Hospital Llandough

Cardiff, CF64 2XX, United Kingdom

Location

University of Glasgow

Glasgow, G12 8TA, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, L14 3PE, United Kingdom

Location

William Harvey Research Institute, Barts and the London Medical School

London, EC1M 6BQ, United Kingdom

Location

St Thomas' Hospital

London, SE1 7EH, United Kingdom

Location

St George's Hospital

London, SW17 0RE, United Kingdom

Location

Hammersmith & Fulham GP Partnership: Richford Gate Medical Practice

London, W6 7HL, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Nottingham University Hospital: QMC Campus

Nottingham, NG7 2UH, United Kingdom

Location

Lister Hospital

Stevenage, SG1 4AB, United Kingdom

Location

Related Publications (2)

• Wych J, Grayling MJ, Mander AP. Sample size re-estimation in crossover trials: application to the AIM HY-INFORM study. Trials. 2019 Dec 2;20(1):665. doi: 10.1186/s13063-019-3724-6.

  PMID: 31791376 DERIVED

• Mukhtar O, Cheriyan J, Cockcroft JR, Collier D, Coulson JM, Dasgupta I, Faconti L, Glover M, Heagerty AM, Khong TK, Lip GYH, Mander AP, Marchong MN, Martin U, McDonnell BJ, McEniery CM, Padmanabhan S, Saxena M, Sever PJ, Shiel JI, Wych J, Chowienczyk PJ, Wilkinson IB. A randomized controlled crossover trial evaluating differential responses to antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity: The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative Markers in HYpertension program-AIM-HY INFORM trial. Am Heart J. 2018 Oct;204:102-108. doi: 10.1016/j.ahj.2018.05.006. Epub 2018 May 20.

  PMID: 30092411 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine; Lisinopril; Amiloride; Chlorthalidone

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Pyrazines; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ian Wilkinson

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant

Study Record Dates

• First Submitted: June 30, 2016
• First Posted: July 28, 2016
• Study Start: November 1, 2016
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

GB (14)