Personalised Electronic Record Supported Optimisation of Amlodipine for Patients With Hypertension (PERSONAL HTN)

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

Study Overview

• Status: Withdrawn
• Conditions: Hypertension
• Intervention / Treatment: Drug: Amlodipine

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 Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Amlodipine 0mg; 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	Drug: Amlodipine; Amlodipine 1mg/ml Oral Solution
Other: Amlodipine 5mg; 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	Drug: Amlodipine; Amlodipine 1mg/ml Oral Solution

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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
Feasibility of collecting data using a digital diary	Feasibility of collecting data using a digital diary	End of study 1 year
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
Patient feedback on the use of digital diary	Patient feedback on the use of digital diary	End of study 1 year
Insight into number of patients achieving target BP of <135 and 85 at EOS	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 reduction in systolic BP of ≥5mmHg at EOS	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 ≥10mmHg 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 diastolic BP of ≥5mmHg at EOS	Insight into number of patients achieving reduction in diastolic BP of ≥5mmHg at EOS	End of study 1 year

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: INNOVATEUK; Closed Loop Medicine Ltd
• Investigators: Principal Investigator: David Collier, Dr, Clinical Director

Study record dates

Study Major Dates

• Study Start (Estimated): September 26, 2020
• Primary Completion (Estimated): January 31, 2021
• Study Completion (Estimated): May 31, 2021

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 27, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Calcium Channel Blockers; Vasodilator Agents; Antihypertensive Agents; Amlodipine
• Other Study ID Numbers: 1 (Mobile Health and Wellness Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Main study findings will be published on websites of the cardiovascular unit at Barts. Following primary publication of the trial results, fully anonymized trial data can be made available to interested researchers on request to the Chief Investigator.

The sponsor retains the right to review all publications prior to submission or publication. Responsibility for ensuring accuracy of any publication from this study is delegated to the Chief Investigator.

• IPD Sharing Time Frame: Post-trial, timeframe unspecified
• IPD Sharing Access Criteria: Approved authorised by CI and clinical/research team.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No