UMIN-CTR Clinical Trial

Public title

Effective Treatment for Elevated Nighttime-Home Blood Pressure in Patients with Hypertension (Prognostic Value of Nighttime Home Blood Pressure Reduction)

Acronym

Treatment for Elevated Nighttime-Home Blood Pressure in Hypertensive Patients

Scientific Title

Effective Treatment for Elevated Nighttime-Home Blood Pressure in Patients with Hypertension (Prognostic Value of Nighttime Home Blood Pressure Reduction)

Scientific Title:Acronym

Treatment for Elevated Nighttime-Home Blood Pressure in Hypertensive Patients

Region

Japan

Condition

Hypertension

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

(1)To investigate whether elevated nighttime-home blood pressure assessed by a home blood pressure device can be reduced by aggressive antihypertensive therapy in patients with hypertension.
(2)To evaluate the effect of reduction of nighttime-blood pressure by aggressive antihypertensive therapy on future cardiovascular events.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

(1) Proportion of patients whose elevated nighttime-systolic blood pressure (>or=120 mmHg) was reduced within the normal range (<120 mmHg) after 6-month agressive antihypertensive therapy.
(2)Effective combination, dose, and dosing time of antihypertensive agents.

Key secondary outcomes

(1)All fatal or nonfatal cardiovascular events (cerebravascular disease, coronary heart disease, death due to heart failure, and sudden death)
(2)New onset of left ventricular hypertrophy and atrial fibrillation
(3)New onset of diabetes mellitus
(4)New onset of proteinuria and impairement of kidney function
(5)Change of endothleial function assessed by flow-mediated vasodilation
(6)Adverse events

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Nighttime-blood pressure was measured using the home blood pressure device (HEM-7252G-HP; Omron, Kyoto, Japan) at 2:00, 3:00, 4:00, and 5 AM (4 points) for consecutive 7 days (at leaset more than 5 days). Nocturnal hypertension was defined as the average of all systolic blood pressure readings >or=120 mmHg. All patients with nocturnal hypertension receive aggressive antihypertensive therapy for 6 month to achieve target nighttime-home systolic blood pressure <120 mmHg. During treatment, nignttime-home blood pressure was measured at 2 month and 6 month just before hospital visiting for 5-7 days. If the nighttime-blood pressure was not normalized at 2 month, it should be measured at 4 month. Investigators are encouraged to adjust antihypertensive therapy at their discretion to achieve the target level of nightime-home systolic blood pressure every 1 month. The time of administration may be changd from morning to evening, using long-acting antihypertensive agents, the dose split into morning and evening or an additional dose taken in the evening or before going to bed.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patietns with hypertension defined in the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH2014) as a clinic systolic blood pressure of 140 mmHg or more and/or a diastolic blood pressure of 90 mmHg or more, or a home systolic blood pressure of 135 mmHg or more and/or a diastolic blood pressure of 85 mmHg or more who have been receiving antihypertensive therapy for more than 3 months.
(2)Patients who can be followed up for 5 years
(3)Patients who have given written informed consent to participate in the study

Key exclusion criteria

(1)Patients with severe valvular heart disease
(2)Patients with moderate or severe cardiac dysfunction (NYHA class III or IV)
(3)Patients with lethal arrhythmia after receiving implantable cardioverter defibrillator
(4)Patients with end-stage renal disease receiving dialysis
(5)Patients with malignant disease
(6)Patients receiving corticosteroid or immunosuppressive agent
(7)Patients with hepatic cirrhosis
(8)Pregnant, possible pregnant, or lactating women
(9)Patients who are considered not eligible for the study by the attending doctor due to other reasons

Target sample size

1000

Name of lead principal investigator

1st name	Tatsuya
Middle name
Last name	Maruhashi

Organization

Hiroshima University

Division name

Department of Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine

Zip code

734-8553

Address

1-2-3 Kasumi, Minami-ku, Hiroshima

TEL

082-257-5540

Email

55maruchin@gmail.com

Name of contact person

1st name	Tatsuya
Middle name
Last name	Maruhashi

Organization

Hiroshima University

Division name

Department of Regeneration and Medicine, Research Center for Radiation Genome Medicine, Research Ins

Zip code

734-8553

Address

1-2-3 Kasumi, Minami-ku, Hiroshima

TEL

082-257-5540

Homepage URL

Email

55maruchin@gmail.com

Institute

Department of Cardiovascular Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University

Institute

Department

Personal name

Organization

none

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Hiroshima University hospital IRB

Address

1-2-3 Kasumi, Minami-ku, Hiroshima

Tel

082-257-5596

Email

hugcp@hiroshima-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

鈴川内科循環器科（広島県）、木下循環器・内科（広島県）、福永循環器・内科（広島県）、吉田内科循環器科（広島県）、みつだ循環器科内科（広島県）、中丸クリニック（広島県）、八田医院（広島県）、重信医院（広島県）、山本内科循環器科（広島県）、日下医院（広島県）、二宮内科（広島県）、梶山内科医院（広島県）、小田内科クリニック（広島県）、小園内科・循環器科（広島県）、よしだハートクリニック（広島県）、大岩内科（広島県）、松本内科循環器科医院（広島県）、かわごえ循環器内科（広島県）、しみずハート内科クリニック（広島県）、ＪＡ広島総合病院（広島県）、県立広島病院（広島県）、広島赤十字・原爆病院（広島県）、土谷総合病院（広島県）、呉共済病院（広島県）、済生会呉病院（広島県）、マツダ病院（広島県）

Date of disclosure of the study information

2015

Year

09

Month

30

Day

URL releasing protocol

https://journals.lww.com/jhypertension/fulltext/2025/05000/nighttime_blood_pressure_targeted_antihyp

Publication of results

Partially published

URL related to results and publications

https://journals.lww.com/jhypertension/fulltext/2025/05000/nighttime_blood_pressure_targeted_antihyp

Number of participants that the trial has enrolled

447

Results

264 hypertensive patients receiving antihypertensive medication were enrolled to evaluate the efficacy and safety of intensive antihypertensive treatment targeting nighttime systolic blood pressure (SBP). 90 patients with nocturnal hypertension at baseline (defined as nighttime SBP > or = 120 mmHg) underwent aggressive medication adjustments over a 6-month period. Nocturnal hypertension was normalized in 48 patients (53.3%), with nighttime SBP decreasing from 127.8 to 112.5 mmHg.

Results date posted

2025

Year

04

Month

07

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2025

Year

03

Month

01

Day

Baseline Characteristics

A total of 264 Japanese patients with hypertension who were receiving antihypertensive treatment participated in this study. The mean age was 68.5 years, and 61.0% were male. The average body mass index (BMI) was 24.3. Regarding comorbidities, dyslipidemia was the most prevalent (79.5%), followed by chronic kidney disease (28.2%), diabetes mellitus (21.7%), coronary heart disease (13.8%), cerebrovascular disease (12.0%), and sleep apnea syndrome (12.0%). Additionally, 47.3% of the participants had a history of smoking.

All participants were taking antihypertensive medications, with calcium channel blockers being the most commonly used (83.3%), followed by angiotensin II receptor blockers (72.0%), B-blockers (14.4%), diuretics (21.6%), and mineralocorticoid receptor antagonists (4.5%). With respect to dosing time, 73.1% of the patients took their medication in the morning, and 42.8% took it at bedtime.

At baseline, the mean systolic blood pressure (SBP) measured in the clinic was 128.8 mmHg. Home blood pressure monitoring showed an average nighttime SBP of 116.6 mmHg, morning SBP of 129.5 mmHg, and evening SBP of 124.1 mmHg.

Among the participants, 90 patients (34.1%) had nocturnal hypertension, defined as nighttime SBP > or = 120 mmHg. Compared with those without nocturnal hypertension, these patients were older, had lower estimated glomerular filtration rate (eGFR), and had a higher prevalence of cerebrovascular disease. Moreover, the proportion of patients taking antihypertensive medication at bedtime was lower in the nocturnal hypertension group.

Participant flow

This prospective, multicenter study was conducted between October 2015 and March 2019 at six hospitals and nine affiliated clinics in Hiroshima Prefecture. Eligible participants were adults aged 20 years or older who had been diagnosed with hypertension according to the Japanese Society of Hypertension guidelines and had been receiving antihypertensive treatment for at least three months.

After screening and applying the exclusion criteria, a total of 264 patients were enrolled in the study.

Among them, 90 patients were found to have nocturnal hypertension at baseline, defined as a nighttime systolic blood pressure (SBP) of > or = 120 mmHg. These patients underwent aggressive adjustments in antihypertensive medication targeting nighttime BP. The remaining 174 patients did not have nocturnal hypertension and received usual care with routine follow-up.

At the 6-month follow-up, 48 out of the 90 patients (53.3%) in the intervention group achieved normalization of nocturnal hypertension, while 42 patients (46.7%) continued to have elevated nighttime BP.

Adverse events

In this study, serious adverse events were very rare, occurring in approximately 2% of both the nocturnal hypertension and non-nocturnal hypertension groups, and none were considered related to the intervention targeting nighttime blood pressure.

Non-serious adverse events were more frequent in the nocturnal hypertension group (40%) compared to the non-nocturnal hypertension group (28.2%). The most commonly reported event was orthostatic dizziness, but this and other events observed were not specific to nighttime BP-targeted treatment and are commonly encountered during routine intensification of antihypertensive therapy.

These findings suggest that antihypertensive treatment targeting nighttime blood pressure can be implemented safely.

Outcome measures

Primary Endpoint
The proportion of patients with nocturnal hypertension who achieved the target nighttime systolic blood pressure (SBP <120 mmHg) after 6 months of intervention.

Secondary Endpoints
Identification of effective antihypertensive treatment strategies that contributed to the normalization of nighttime BP.

The impact of nighttime BP-targeted intervention on morning and evening home BP levels.

The incidence and nature of serious and non-serious adverse events during the intervention period.

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2015

Year

09

Month

25

Day

Date of IRB

2015

Year

09

Month

14

Day

Anticipated trial start date

2015

Year

10

Month

01

Day

Last follow-up date

2024

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Patients were followed up.

Registered date

2015

Year

09

Month

30

Day

Last modified on

2025

Year

04

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022103