Clinical trial NCT02214498: Treatment of HYpertension: Morning Versus Evening
Official title: Treatment of HYpertension: Morning Versus Evening
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Essential Hypertension
Keywords: Dipper
Non-dipper
Chronopharmacology
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2014-08-12
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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

Primary outcomes:
measure: Average nocturnal blood pressure, percentage dipping and nadir of nocturnal blood pressure
timeFrame: 24 hours
Secondary outcomes:
measure: Percentage of nocturnal diastolic blood pressure measurements below 65 mm hg
timeFrame: 24 hours
measure: Urine: Sodium, potassium, protein, melatonin, creatinin
timeFrame: Two times within 24 hours at the end of six weeks of treatment according to one of the two regimes
measure: Plasma: enalapril, cortisol, melatonin, aldosterone, ACE activity, gene expression of clock genes
timeFrame: Moring of 24 hour blood pressure measurement after six weeks of treatment according to a certain regime
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
Study officials:
affiliation: Erasmus Medical Center
name: Jorie Versmissen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmus Medical Center
name: Teun Van Gelder, Prof
role: STUDY_DIRECTOR
affiliation: Erasmus Medical Center
name: Eric Sijbrands, Prof
role: STUDY_CHAIR
References: