Personalised Electronic Record Supported Optimisation of Amlodipine for Patients With Hypertension

Phase 4

Withdrawn

• Conditions: Hypertension
• Interventions: Drug: Amlodipine

• Registration Number: NCT06713785
• Lead Sponsor: Queen Mary University of London

Brief Summary

The primary objective of the study is to assess precision dosing of amlodipine to deliver reductions in blood pressure in patients with primary hypertension and inadequate BP control by up-titration of amlodipine in 1mg increments

Detailed Description

Hypertension is the leading preventable cause of premature death worldwide. Globally, 1.39bn people are estimated to have hypertension, and it caused ≈10.7 million deaths in 2015. It is projected to affect more than 1.5 billion people around the world by 2025.

In the UK \~30% of adults have hypertension3; 9.5m have a diagnosis, and a further 5m people in England alone may have hypertension yet be unaware. The annual incidence of new cases is 5-8%5. Physician inertia (inadequate up-titration of treatment, especially from monotherapy) and poor patient adherence to treatment (especially when based on multiple pills) are now recognised as major factors contributing to poor BP control.

Amlodipine is a calcium-channel blocking drug which reduces blood pressure by relaxing blood vessels (especially veins) but this same effect makes it prone to causing fluid accumulation (oedema) in the lower limbs. Approved by the FDA in the United States in 1987, there is a large amount of evidence on its effectiveness and safety in reducing blood pressure and in treating stable angina. There appears to be a close relationship between wanted and unwanted effects. Finding the best dose of amlodipine for a patient could be useful in optimizing their blood pressure treatment. At present the tablet doses available are only 5mg and 10mg in the UK.

In the present study the investigators will investigate the relationship between patient beliefs about medicines using the Beliefs about Medicines Questionnaire (BMQ) developed by Horne, Weinman and Hankins (1999)13 and their adherence using the Morisky Medication Adherence Scale - 8 14. The investigators hypothesize that patients' tolerability of side effects (as measured by VAS) will be related to their beliefs about the necessity of medication (necessity concerns), their concerns about side effects and their adherence to medication.

This study will only look at doses within the current maximum licensed 10mg dose. The investigators will ask patients who have had previous problems with unwanted effects of amlodipine at conventional doses to have careful monitoring of blood pressure over 24 hours using an ambulatory blood pressure monitor. If blood pressure control on their maximum tolerated conventional dose of amlodipine (0 or 5mg) is inadequate (systolic daytime average =\>135 mmHg and/or diastolic daytime average =\>85 mmHg), then patients will be eligible for the study. Those taking 5mg amlodipine tablets daily will be given amlodipine liquid to take at the same 5mg dose to convert to liquid formulation dosing. Patients will be issued with standard home blood pressure monitors and will be asked to measure their blood pressure in the morning (three readings) before taking their tablet (trough treatment) and again in the evening (three readings). Patients will attend every two weeks, following screening with clinical history taking, haematology, biochemistry, HbA1c, routine physical examination and resting ECG. Every two weeks patients will have clinic blood pressure measurements and review of home BP monitoring

Study Timeline

• Study First Submitted: 2019-11-14
• Study Start: 2020-09-26
• Primary Completion: 2021-01-31
• Study Completion: 2021-05-31
• Status Verified: 2024-11
• Study First Submitted QC: 2024-11-27
• Last Update Submitted: 2024-11-27
• Study First Posted: 2024-12-03
• Last Update Posted: 2024-12-03

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• • Age ≥18 years to 75 years
• Able to give consent
• Possession of a smart phone
• Confirmed diagnosis of hypertension by NICE/BIHS criteria on either 24h ABPM or repeated home measures of blood pressure, at any time.
• Previous experience of amlodipine and unwanted effects of the drug
• Willing to be re-challenged with amlodipine (if off treatment) or to try a higher dose than the 5mg currently treated with.
• Sub-optimal blood pressure control defined as daytime ABPM average systolic blood pressure of 135mmHg or greater, and/or daytime ABPM average diastolic blood pressure of 85mmHg or greater.
• Stable antihypertensive medication (ie. no dose adjustments, new Rx or stopped Rx in last 4 weeks for CCB, 8 weeks for diuretics, ACEi, ARB).
• Patients may be taking other blood pressure lowering medication, but these must be kept stable during assessment of eligibility and for the duration of the trial (except where essential to maintain patient safety).

Exclusion Criteria

• • Unable to consent.
• Severe adverse reaction to amlodipine making re-challenge or dose increase unwise.
• Myocardial infarction, Acute Coronary Syndrome, stroke or Transient Ischaemic Attack in the 6 months prior to screening.
• Heart failure classed as NYHA class III or IV.
• Renal impairment with eGFR < 30ml/minute.
• Participation in another clinical trial, where the patient has received IMP in the last 3 months, except for MRC Aim-Hy with established medications and where patients can be screened after 6 weeks from final visit.
• Pregnant or lactating or female of childbearing potential not using adequate contraception

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Amlodipine 0mg	Amlodipine	amlodipine dose 0mg Week 0 → 1mg Week 2 → 2mg Week 4 → 3mg Week 6 → 4mg Week 8 → 5mg Dose escalation to continue in 1mg increments to a maximum of 5mg
Amlodipine 5mg	Amlodipine	amlodipine dose 5mg Week 0 → 6mg Week 2 → 7mg Week 4 → 8mg Week 6 → 9mg Week 8 → 10mg Dose escalation to continue in 1mg increments to a maximum of 10mg

Primary Outcome Measures

Name	Time	Method
The difference in daytime ambulatory systolic blood pressure between baseline ABPM and post-titration ABPM on a personalized dose of amlodipine.	End of study 1 year	pressure between baseline ABPM and post-titration ABPM on a personalized dose of amlodipine.

Secondary Outcome Measures

Name	Time	Method
Insight into number of patients achieving reduction in diastolic BP of ≥5mmHg at EOS	End of study 1 year	Insight into number of patients achieving reduction in diastolic BP of ≥5mmHg at EOS
Other clinically significant blood pressure measures which related to difference in measured blood pressure between baseline and EOS, especially AOBP clinic BP readings and home BP readings	End of study 1 year	Other clinically significant blood pressure measures which related to difference in measured blood pressure between baseline and EOS, especially AOBP clinic BP readings and home BP readings
Feasibility of collecting data using a digital diary	End of study 1 year	Feasibility of collecting data using a digital diary
Collect patient reported outcome data including satisfaction with medication regime using digital diary	Collect patient reported outcome data including satisfaction with medication regime using digital diary	Collect patient reported outcome data including satisfaction with medication regime using digital diary
Insight into number of patients achieving target BP of <135 and 85 at EOS	End of study 1 year	Insight into number of patients achieving target BP of \<135 and 85 at EOS
Patient feedback on the use of digital diary	End of study 1 year	Patient feedback on the use of digital diary
Insight into number of patients achieving reduction in systolic BP of ≥5mmHg at EOS	End of Study	Insight into number of patients achieving reduction in systolic BP of ≥5mmHg at EOS
Insight into number of patients achieving reduction in systolic BP of ≥10mmHg EOS	EOS 1 year	Insight into number of patients achieving reduction in systolic BP of ≥10mmHg EOS