Essential HypertensionPhase 4THYMENCT02214498
Treatment of HYpertension: Morning Versus Evening
A Phase 4 study testing Enalapril/hydrochlorothiazide in people with Essential Hypertension, run by Erasmus Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- Enalapril/hydrochlorothiazide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2015to May 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Jorie Versmissen, MD, PhD contact
Netherlands1 site
Erasmus MC
Rotterdam
Jorie Versmissen, MD, PhD, j.versmissen@erasmusmc.nl
Jorie Versmissen, MD, PhD
About this study
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.
Read more
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
- Being tested
- Enalapril/hydrochlorothiazide, Placebo
- Keywords
- Dipper, Non-dipper, Chronopharmacology
- Medical subject headings
- Essential Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enalapril/hydrochlorothiazideDrug
Also called To be determined
The intervention implies that morning and evening administration of enalapril/hydrochlorothiazide will be compared
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Enalapril/hydrochlorothiazide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 hours
Secondary outcomes (3)
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.
Measured: 24 hours
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
Measured: 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
Measured: Moring of 24 hour blood pressure measurement after six weeks of treatment according to a certain regime
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2014 (estimated)
- Study startMay 2015
- Primary completionMay 2017 (estimated)
- Study completionMay 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, Jorie Versmissen, Erasmus Medical Center
- Investigators
- Jorie Versmissen, MD, PhD, Principal investigator, Erasmus Medical CenterTeun Van Gelder, Prof, Study director, Erasmus Medical CenterEric Sijbrands, Prof, Study chair, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02214498
- Sponsor's protocol ID
- 2014_THYME
- Acronym
- THYME
- Status last verified
- Aug 2014
- First submitted
- 8 Aug 2014
- Last updated
- 15 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of HYpertension: Morning Versus Evening
- ClinicalTrials.gov ID
- NCT02214498
- Acronym / sponsor ID
- THYME / 2014_THYME
- Conditions
- Essential Hypertension
- Keywords
- Dipper, Non-dipper, Chronopharmacology
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- May 2015
- Primary completion
- May 2017 (estimated)
- Study completion
- May 2017 (estimated)
- First posted
- 12 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enalapril/hydrochlorothiazide | Active comparator | Drug: Enalapril/hydrochlorothiazide, Drug: PlaceboThis 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 |
| Placebo | Placebo comparator | Drug: Enalapril/hydrochlorothiazide, Drug: PlaceboThis 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 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enalapril/hydrochlorothiazideAlso: To be determinedThe intervention implies that morning and evening administration of enalapril/hydrochlorothiazide will be compared | Drug | Enalapril/hydrochlorothiazide, Placebo |
| Placebo | Drug | Enalapril/hydrochlorothiazide, Placebo |
Primary outcome
Average nocturnal blood pressure, percentage dipping and nadir of nocturnal blood pressure
Time frame: 24 hours
At the end of each treatment period of six weeks, a 24 hour ambulatory blood pressure measurement will be performed
3 secondary outcomes
Percentage of nocturnal diastolic blood pressure measurements below 65 mm hg
Time frame: 24 hours
Urine: Sodium, potassium, protein, melatonin, creatinin
Time frame: 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
Time frame: Moring of 24 hour blood pressure measurement after six weeks of treatment according to a certain regime
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorie Versmissen, MD, PhD contact
Jorie Versmissen, MD, PhD principal investigator
Erasmus Medical Center
Teun Van Gelder, Prof study director
Erasmus Medical Center
Eric Sijbrands, Prof study chair
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Enalapril/hydrochlorothiazide in people with Essential Hypertension, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jorie Versmissen, MD, PhD (j.versmissen@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average nocturnal blood pressure, percentage dipping and nadir of nocturnal blood pressure (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2014.