UMIN-CTR Clinical Trial

Public title

Hypertension and Atrial Fibrillation treated by Rivaroxaban for the Morning and Night with sYnergy with calcium antagonists

Acronym

Hypertension and Atrial Fibrillation treated by Rivaroxaban for the Morning and Night with sYnergy with calcium antagonists; HARMONY

Scientific Title

Hypertension and Atrial Fibrillation treated by Rivaroxaban for the Morning and Night with sYnergy with calcium antagonists

Scientific Title:Acronym

Hypertension and Atrial Fibrillation treated by Rivaroxaban for the Morning and Night with sYnergy with calcium antagonists; HARMONY

Region

Japan

Condition

Non-valvular atrial fibrillation (newly diagnosed patients; or patients taking an oral anticoagulant drug, and their primary physicians consider that switching to rivaroxaban is appropriate)

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To study the effect of the oral factor Xa inhibitor rivaroxaban administered once daily on changes in coagulation/ fibrinolysis markers in patients with non-valvular atrial fibrillation; To study changes in coagulation/fibrinolysis markers following concurrent administration of rivaroxaban and nifedipine CR to non-valvular atrial fibrillation patients in which early-morning hypertension (morning surge in blood pressure) has been detected by home blood pressure measurement

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Early-morning F1+2 before and after the rivaroxaban administration

Key secondary outcomes

1) Change in factor Xa activity (%)
2) Changes in other coagulation and fibrinolysis markers: PT-INR (Prothrombin Time-International Normalized Ratio), aPTT (activated partial thromboplastin time), d-Dimer, TAT, and soluble fibrin monomer complex (SFMC)
3) Changes in cardiomyopathy markers: NT-proBNP, Troponin T
4) Occurrence/exacerbation of cerebro/cardiovascular events*1
5) Blood pressure (outpatient measurement at hospital visits), home blood pressure
6) Changes of coagulation and fibrinolysis markers in patients who underwent ablation or electrical cardioversion
7) Adverse events: Major bleeding events (ISTH criteria)*2, other bleeding events (such as GI bleeding, nasal bleeding, gingival bleeding, subcutaneous bleeding, and hematuria)*2, gastrointestinal symptoms, abnormalities in laboratory test values, etc.

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

Xarelto Tablets (10mg or 15 mg as rivaroxaban) is continuously administered once daily after breakfast over 8 weeks (study period I).

To subjects who have shown early-morning hypertension in the study period I, Adalat-CR Tablets (20-40 mg as nifedipine) is additionally administered at bedtime, and the Xarelto Tablets administration is continued for additional 8 weeks.

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

50

years-old

<=

Age-upper limit

85

years-old

>

Gender

Male and Female

Key inclusion criteria

Patients who meet all of the following criteria at institutions participating in the study
(1) Patients newly diagnosed with non-valvular atrial fibrillation (NVAF), or those diagnosed with non-valvular atrial fibrillation in the past and are receiving an oral anticoagulant drug
(2) Patients diagnosed with hypertension, regardless of treatment with an antihypertensive drug
(3) Poorly controlled patients if being treated with warfarin
(4) Patients who can measure home blood pressure
(5) Male or female patients at least 50 years old and less than 85 years old
(6) Patients who have consented in writing

Key exclusion criteria

Patients who meet any of the following criteria are not included in the study subjects.
(1) Patients with cerebral stroke or systemic embolism that has occurred within the last 6 months
(2) Patients with myocardial infarction, unstable angina, or a peripheral artery disease that has developed within the last 6 months
(3) Patients with acute-phase heart failure
(4) Hypertensive patients with an office systolic blood pressure of >=140mmHg even after treatment with an antihypertensive drug
(5) Patients with renal failure (creatinine clearance, less than 30 mL/min)
(6) Patients requiring two or more antiplatelet agents (concomitant use)
(7) Patients who is using an anticoagulant drug other than dabigatran and warfarin
(8) Patients requiring administration of an HIV protease inhibitor (oral drug)
(9) Patients requiring administration of an azole antifungal agent (oral, or injection (except fluconazole))
(10) Patients being treated for malignant tumors
(11) Patients who have undergone a surgery within the last 6 months
(12) Patients with a rheumatic disease
(13) Contraindicated cases of the study drugs
(14) Patients who are pregnant or breast-feeding
(15) Other patients that an investigator finds inappropriate to be included in the study population

Target sample size

100

Name of lead principal investigator

1st name
Middle name
Last name	Kazuomi Kario

Organization

Jichi Medical University School of Medicine

Division name

Division of Cardiovascular Medicine, Department of Medicine,

Zip code

Address

3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, JAPAN

TEL

0285-58-7538

Email

kkario@jichi.ac.jp

Name of contact person

1st name
Middle name
Last name	Tomoyuki Kabutoya

Organization

Jichi Medical University School of Medicine

Division name

Division of Cardiovascular Medicine, Department of Medicine,

Zip code

Address

3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, JAPAN

TEL

0285-58-7344

Homepage URL

Email

kabu@jichi.ac.jp

Institute

Jichi Medical University School of Medicine

Institute

Department

Personal name

Organization

Bayer Yakuhin, Ltd

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Sogo Rinsho Medefi Co., Ltd.

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

自治医科大学（栃木県）
下田メディカルセンター（静岡県）
中村循環器科心臓外科医院（福岡県）
おんが病院（福岡県）
海老名総合病院（神奈川県）
倉井清彦内科医院（栃木県）
天使病院（北海道）
鶴見中央クリニック（神奈川県）
いつき会ハートクリニック（東京都）
二本松病院（福島県）
南会津病院（福島県）
白河市表郷クリニック（福島県）
会田病院（福島県）
東北公済病院（宮城県）

Date of disclosure of the study information

2014

Year

11

Month

30

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

11

Month

05

Day

Date of IRB

Anticipated trial start date

2014

Year

12

Month

01

Day

Last follow-up date

2017

Year

08

Month

31

Day

Date of closure to data entry

Date trial data considered complete

2017

Year

08

Month

01

Day

Date analysis concluded

Other related information

Registered date

2014

Year

11

Month

28

Day

Last modified on

2018

Year

12

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018357