UMIN-CTR Clinical Trial

Basic information
Public title	An analysis on distribution of serum concentration of bisoprolol and its effect on prognosis in patients with heart failure
Acronym	CVI ARO 6 study
Scientific Title	An analysis on distribution of serum concentration of bisoprolol and its effect on prognosis in patients with heart failure
Scientific Title:Acronym	CVI ARO 6 study
Region	Japan

Condition
Condition	Patients with heart failure who are taking bisoprolol
Classification by specialty	Cardiology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To clarify the distribution of trough serum concentration of bisoprolol and its relationship with prognosis.
Basic objectives2	PK,PD
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Others
Developmental phase	Not applicable

Assessment
Primary outcomes	Admission or death by heart failure within 1 year after registration
Key secondary outcomes	Primary outcomes and increase of diuretics due to exacerbation of heart failure (loop diuretics, potassium sparing diuretics, thiazide diuretics, selective vasopressin V2-receptor antagonists)

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
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

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients who are visiting to the Cardiovascular Institute and taking bisoprolol with diagnosis of heart failure. Patients who meets all of the criteria below. (1) Age: 20 years and older (2) In ultrasound cardiogram within 1 year before registration (if multiple data exists, the latest one), systolic dysfunction (left ventricular ejection fraction [LVEF] <50%), or diastolic dysfunction (LVEF >=50% and E/E' >=15) are observed. (3) Bisoprolol is constantly taken for more than 1 month at blood sampling of serum concentration. (4) Bisoprolol is administered once a day. (5) Outpatients
Key exclusion criteria	(1) Inpatients at blood sampling of serum concentration (2) Dose of bisoprolol was changed within 1 month before blood sampling of serum concentration. (3) Bisoprolol was administered twice a day within 1 week before blood sampling of serum concentration. (4) Hyperthyroidism is diagnosed or suspected. (5) Patients who meet contraindications below: 1) Patients with advanced bradycardia (significant sinus bradycardia), atrioventricular block (II or III degree) , atrioventricular block, and/or sick sinus syndrome 2) Patients with diabetic ketoacidosis, and/or metabolic acidosis 3) Patients with cardiogenic shock 4) Patients with right-sided heart failure by pulmonary hypertension 5) Patients with heart failure requiring intravenous administration of inotropic agents and/or vasodilatory agents 6) Patients with decompensated heart failure 7) Patients with severe peripheral circulatory disturbance 8) Patients with untreated pheochromocytoma 9) Women who are pregnant or may be pregnant 10) Patients who have a history of hypersensitivity for bisoprolol (6) Patients who are judged by the researchers as inadequate for this study
Target sample size	240

Research contact person
Name of lead principal investigator	1st name Shinya Middle name Last name Suzuki
Organization	The Cardiovascular Institute
Division name	Department of cardiovascular medicine
Zip code	106-0031
Address	3-2-19 Nishiazabu, Minato-Ku, Tokyo. ZIP: 106-0031
TEL	+81-3-3408-2151
Email	sinsuz-tky@umin.net

Public contact
Name of contact person	1st name Kazumi Middle name Last name Matsuda
Organization	Cardiovascular Institute Academic Research Organization (CVI ARO)
Division name	Head office
Zip code	106-0031
Address	3-2-19 Nishiazabu, Minato-Ku, Tokyo
TEL	+81-3-3408-2151
Homepage URL
Email	matsuda@cvi.or.jp

Sponsor
Institute	The Cardiovascular Institute
Institute
Department

Funding Source
Organization	Mitsubishi Tanabe Pharma
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Ethical Committee of The Cardiovascular Institute
Address	Nishi-azabu 3-2-19, Minato-ku, Tokyo
Tel	03-3408-2151
Email	matsuda@cvi.or.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	心臓血管研究所付属病院（The Cardiovascular Institute）

Other administrative information
Date of disclosure of the study information	2016 Year 07 Month 27 Day

Related information
URL releasing protocol	https://www.cvi.or.jp/kenkyujo/cviaro.html#link01
Publication of results	Published

Result
URL related to results and publications	https://www.sciencedirect.com/science/article/abs/pii/S1347436720300033?via%3Dihub
Number of participants that the trial has enrolled	128
Results	The data of 114 HF patients under once-daily bisoprolol was analyzed. In multivariate logistic regression analysis, independent predictors of high Bis-PC (1st tertile: >= 5.38 ng/mL) were age, eGFR, and bisoprolol dose. The cumulative incidence rates of the primary endpoint were 10.5%/13.2%/26.3% in low/middle/high Bis-PC categories, respectively (log rank test, p = 0.087). Bis-PC was independently associated with the primary endpoint (hazard ratio [HR], 1.19 [per ng/mL], 95% CI 1.03-1.36).
Results date posted	2021 Year 04 Month 22 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2020 Year 01 Month 13 Day
Baseline Characteristics	Heart failure patients prescribed bisoprolol once per day.
Participant flow	Consecutive eligible patients who visited the Cardiovascular Institute were enrolled.
Adverse events	Admission or death by heart failure: 12
Outcome measures	The cumulative incidences of the primary endpoint at 1-year were 10.5%, 13.2%, and 26.3% in patients in the low, middle, and high Bis-PC categories.
Plan to share IPD	Available by the first author for reasonable cases
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 04 Month 20 Day
Date of IRB	2016 Year 05 Month 09 Day
Anticipated trial start date	2016 Year 07 Month 01 Day
Last follow-up date	2017 Year 06 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	The main results were published.

Management information
Registered date	2016 Year 07 Month 27 Day
Last modified on	2021 Year 04 Month 22 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026166