Treatment of HYpertension: Morning Versus Evening

Essential Hypertension Clinical Trial

— THYME  

Official title:

Treatment of HYpertension: Morning Versus Evening

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02214498
• Other study ID #: 2014_THYME
• Status: Not yet recruiting
• Phase: Phase 4
• First received: August 8, 2014
• Last updated: August 13, 2014
• Start date: May 2015
• Est. completion date: May 2017

Study information

• Verified date: August 2014
• Source: Erasmus Medical Center
• Contact: Jorie Versmissen, MD, PhD
• Email: j.versmissen[@]erasmusmc.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

Rationale:

The nocturnal blood pressure mean is an independent and stronger predictor of cardiovascular disease (CVD) risk than either daytime office, awake or 24hour mean blood pressure. In general, when nocturnal blood pressure does not decline CVD risk is higher, usually referred to as "dippers" versus "non-dippers". Evening administration of treatment might lower nocturnal blood pressure more effectively than morning administration, which is most commonly advised.

The main hypothesis of this study is that evening administration of antihypertensive medication might resume the dipping pattern in non-dippers and as a consequence might reduce CVD risk more than morning administration.

Primary objective (in short):

-to prove that evening administration of enalapril/hydrochlorothiazide in non-dippers can resume a dipping blood pressure pattern in non-dippers

Study design: A double-blind placebo-controlled cross-over study Each person will use for one period of six weeks enalapril/hydrochlorothiazide in the morning and placebo in the evening, and one period of six weeks the other way around

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: May 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Essential hypertension

• Stable blood pressure on treatment with Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Blocker (ARB) and hydrochlorothiazide

• Age between 18 and 85 years

• WHO performance status 0-1

• Available for a time period of 15 weeks

• Written informed consent

• Dippers: Nocturnal blood pressure fall of 10-20% of daytime values.20

• Non-dippers: -Nocturnal blood pressure fall of <10% of daytime values

Exclusion Criteria:

• secondary cause of hypertension

• use of ARB because of intolerability (e.g. dry cough) of ACEI

• nocturnal blood pressure fall of >20% or rise

• renal insufficiency (GFR<60 ml/min)

• shift work

• pregnancy or wish to get pregnant

• use of other antihypertensive medication than ACEI, ARB, hydrochlorothiazide or a calcium channel blocker

• use of sleeping medication

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension

Intervention

Drug:
• Enalapril/hydrochlorothiazide
The intervention implies that morning and evening administration of enalapril/hydrochlorothiazide will be compared
• Placebo

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average nocturnal blood pressure, percentage dipping and nadir of nocturnal blood pressure	At the end of each treatment period of six weeks, a 24 hour ambulatory blood pressure measurement will be performed	24 hours	Yes
Secondary	Percentage of nocturnal diastolic blood pressure measurements below 65 mm hg	One safety issue on evening administration of antihypertensive treatment is that blood pressure might get too low. We will assess this especially in the dippers.	24 hours	Yes
Secondary	Urine: Sodium, potassium, protein, melatonin, creatinin	Excretion of sodium, potassium, protein and melatonin depend on the circadian clock. Therefore, differences between morning and evening administration of antihypertensive medication are tested	Two times within 24 hours at the end of six weeks of treatment according to one of the two regimes	No
Secondary	Plasma: enalapril, cortisol, melatonin, aldosterone, ACE activity, gene expression of clock genes		Moring of 24 hour blood pressure measurement after six weeks of treatment according to a certain regime	No