Anti-hypertensive Medication Dosing Regimen in Effective Blood Pressure Control (HARMONY)

Hellenic Anglo Research Into Morning Or Evening Antihypertensive Drug deliverY Trial

A randomised crossover trial of anti-hypertensive medication dosing regimen in effective blood pressure control.

To investigate whether there is a difference in 24 hour blood pressure (BP) control when antihypertensive medications are taken in the morning compared with the evening.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Anti-hypertensive Medication -

Detailed Description

The identification of any significant difference could lead to more effective therapeutic management of arterial hypertension, which in turn would result in a reduced cardiovascular burden, lower costs and a better quality of life for hypertensive patients.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece
    • Aristotle University Of Thessaloniki
• United Kingdom
  • London, United Kingdom, W2 1LA
    • Imperial Clinical Trials Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Caucasian patients aged 18-80 years;
• History of any grade of hypertension for at least 1 year, including at least 3 months of constant antihypertensive medication (consisting of ≥ 1 antihypertensive drugs, each administered in one dose daily), with reasonably controlled BP (≤150/90 mmHg and ≥ 115/75 mmHg on usual medication) based on previous clinic records, in the last 3 months.

Exclusion Criteria:

• BP levels > 150/90 mmHg or < 115/75 mmHg in the last 3 months.
• Postural hypotension, defined as symptoms resulting from a > 20 mm Hg drop of systolic BP or a > 10 mm Hg drop of diastolic BP or both between 1 and 3 min after standing from the sitting position.
• Known Extreme dippers at baseline (fall of mean night time SBP > 20% of mean day time SBP)
• Individuals with jobs which require night-time shift work.
• Pregnant women or those planning to become pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Evening medication; Anti hypertensive medication in the evening (between 18.00 and 23.00)	Drug: Anti-hypertensive Medication -; Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication. Dosing regimen either in the morning (between 06.00 and 11.00) or in the evening (between 18.00 and 23.00).; Other Names: PR1 Diruetics; PR3 Beta Blockers; PR4 Calcium channel blockers; PR5 ACE inhibitors; PR6 Angiotensin II Receptor Blockers; PR7 Centrally acting agents; PR8 Alpha blockers; PR9 Direct Renin Inhibitors; PR10 Vasodilators
ACTIVE_COMPARATOR: Morning medication; Antihypertensive medication in the morning(between 06.00 and 11.00)	Drug: Anti-hypertensive Medication -; Patients will be taking their routine blood pressure lowering medication prescribed by their GP, different patients will be using different blood pressure lowering medication. Dosing regimen either in the morning (between 06.00 and 11.00) or in the evening (between 18.00 and 23.00).; Other Names: PR1 Diruetics; PR3 Beta Blockers; PR4 Calcium channel blockers; PR5 ACE inhibitors; PR6 Angiotensin II Receptor Blockers; PR7 Centrally acting agents; PR8 Alpha blockers; PR9 Direct Renin Inhibitors; PR10 Vasodilators

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in 24 Hour Systolic Blood Pressure	Changes in 24 hour systolic Blood Pressure using ABPM	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Day-time ABPM Systolic BP		6 months
Mean Day-time ABPM Diastolic BP		6 months
Μean Night Time ABPM Systolic BP		6 months
Μean Night Time ABPM Diastolic BP		6 months
Mean Clinic - Systolic BP	This measure was assessed at a clinic.	6 months
Mean Clinic - Diastolic BP	This measure was assessed at a clinic.	6 months
Self Reported Side Effects	Serious Adverse Events reported during the trial	12 months
Quality of Life Score	Quality of Life Score via questionnaire - EQ-5D-5L Score scale is 0-100, 100 optimal health state.	6 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Aristotle University Of Thessaloniki
• Investigators: Principal Investigator: Neil Poulter, MRCS LRCP MBBS MRCP MSc FRCP, Imperial College London

Publications and helpful links

General Publications

• Lemmer B. Clinical chronopharmacology: the importance of time in drug treatment. Ciba Found Symp. 1995;183:235-47; discussion 247-53. doi: 10.1002/9780470514597.ch13.
• Bruguerolle B. Chronopharmacokinetics. Current status. Clin Pharmacokinet. 1998 Aug;35(2):83-94. doi: 10.2165/00003088-199835020-00001.
• Rothwell PM, Howard SC, Dolan E, O'Brien E, Dobson JE, Dahlof B, Sever PS, Poulter NR. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010 Mar 13;375(9718):895-905. doi: 10.1016/S0140-6736(10)60308-X.
• Smolensky MH, Hermida RC, Ayala DE, Tiseo R, Portaluppi F. Administration-time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. Blood Press Monit. 2010 Aug;15(4):173-80. doi: 10.1097/MBP.0b013e32833c7308.
• Hermida RC, Ayala DE, Mojon A, Fernandez JR. Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study. Chronobiol Int. 2010 Sep;27(8):1629-51. doi: 10.3109/07420528.2010.510230.
• Heart Outcomes Prevention Evaluation Study Investigators; Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000 Jan 20;342(3):145-53. doi: 10.1056/NEJM200001203420301. Erratum In: 2000 May 4;342(18):1376. N Engl J Med 2000 Mar 9;342(10):748.
• Mayet J, Chapman N, Li CK, Shahi M, Poulter NR, Sever PS, Foale RA, Thom SA. Ethnic differences in the hypertensive heart and 24-hour blood pressure profile. Hypertension. 1998 May;31(5):1190-4. doi: 10.1161/01.hyp.31.5.1190.
• Poulter NR, Savopoulos C, Anjum A, Apostolopoulou M, Chapman N, Cross M, Falaschetti E, Fotiadis S, James RM, Kanellos I, Szigeti M, Thom S, Sever P, Thompson D, Hatzitolios AI. Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure. Hypertension. 2018 Oct;72(4):870-873. doi: 10.1161/HYPERTENSIONAHA.118.11101.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2012
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: July 2, 2012
• First Submitted That Met QC Criteria: August 17, 2012
• First Posted (ESTIMATE): August 21, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Antihypertensive Agents; Calcium Channel Blockers; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists
• Other Study ID Numbers: CRO1749

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No