Treatment of HYpertension: Morning Versus Evening

NCT02214498 | Unknown Phase 4

• 1 other identifier: 2014_THYME
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Conditions

Essential Hypertension

Keywords

Dipper; Non-dipper; Chronopharmacology

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Percentage of nocturnal diastolic blood pressure measurements below 65 mm hg

  24 hours

• Urine: Sodium, potassium, protein, melatonin, creatinin

  Two times within 24 hours at the end of six weeks of treatment according to one of the two regimes

• 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

Study Arms (2)

Enalapril/hydrochlorothiazide

ACTIVE COMPARATOR

This arm will start with six weeks of administration of enalapril/hydrochlorothiazide in the evening and placebo in the morning, followed by six weeks of active treatment in the morning and placebo in the evening

Drug: Enalapril/hydrochlorothiazide; Drug: Placebo

Placebo

PLACEBO COMPARATOR

This arm will start with six weeks of morning administration of enalapril/hydrochlorothiazide in the morning and placebo in the evening, followed by six weeks of placebo in the morning and active treatment in the evening

Drug: Enalapril/hydrochlorothiazide; Drug: Placebo

Interventions

Enalapril/hydrochlorothiazide DRUG

The intervention implies that morning and evening administration of enalapril/hydrochlorothiazide will be compared

Also known as: To be determined

Enalapril/hydrochlorothiazide; Placebo

Placebo DRUG

Enalapril/hydrochlorothiazide; Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Erasmus Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Erasmus MC

Rotterdam, Netherlands

Location

MeSH Terms

Conditions

Essential Hypertension

Interventions

Vaseretic

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jorie Versmissen, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Teun Van Gelder, Prof

  Erasmus Medical Center

  STUDY DIRECTOR

• Eric Sijbrands, Prof

  Erasmus Medical Center

  STUDY CHAIR

Central Study Contacts

Jorie Versmissen, MD, PhD

CONTACT

j.versmissen@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: August 8, 2014
• First Posted: August 12, 2014
• Study Start: May 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: August 15, 2014

Record last verified: 2014-08

Locations

NL (1)