UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	The effect of Landiolol hydrochloride administrated in the perioperative period of off-pump coronary artery bypass graft surgery on prevention of atrial fibrillation or atrial flutter
Title of the study (Brief title)	JL-KNIGHT study II (Japan Landiolol-Kicking off the novel investigation for gold standard heart study II)
Region	Japan

Condition
Condition	Patients undergoing off-pump coronary artery bypass graft surgery (CABG)
Classification by specialty	Cardiology Anesthesiology Cardiovascular surgery Intensive care medicine
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigate the efficacy of the perioperative intravenous administration of short-acting beta 1-adrenergic receptor antagonist, Landiolol hydrochloride on the prevention of atrial fibrillation or atrial flutter in the postoperative period of off-pump coronary artery bypass graft surgery
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase IV

Assessment
Primary outcomes	Number of patients with atrial fibrillation or atrial flutter persisting for more than 1 minute in 6 days after surgery
Key secondary outcomes	-Number of patients with atrial fibrillation or atrial flutter in 6 days after surgery -Heart rate and blood pressure -Length of stay in intensive care unit after surgery -Length of stay at hospital after surgery -In-hospital medical expense after surgery -Plasma level of brain natriuretic peptide (BNP) or N-terminal prohormone of BNP (NT-proBNP) -Number of patients with major adverse cerebral and cardiovascular events -Extent of cerebral infarction evaluated by brain magnetic resonance imaging (MRI) -Visual analogue scale (VAS) score for subjective assessment of anastomosis during surgical operation -Motion analysis of anastomotic part of coronary artery -Evaluation of coronary artery bypass graft patency by angiography

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Single blind -participants are blinded
Control	Placebo
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Each subject will be administered Landiolol intravenously at a rate of 3 micrograms/kg/min (0.06 mL/kg/hr) just after anesthetic induction. Heart rate should be maintained at a level between 50 and 80 bpm. The infusion rate of Landiolol can be increased by a rate of 1 microgram/kg/min (0.02 mL/kg/hr) when heart rate is over 80 bpm for 15 or 20 minutes and decreased by a rate of 0.5-1 micrograms/kg/min (0.01-0.02 mL/kg/hr) when the heart rate obviously tend to decrease even within the target heart rate (50-80 bpm). Infusion of Landiolol should be maintained within a rate of 0.5-20 micrograms/kg/min (0.01-0.4 mL/kg/hr) for 24 hours. Medical treatment using atropine or ephedrine etc. or pacing therapy will be performed when heart rate is under 50 bpm, however infusion of Landiolol has to be maintained with minimum rate (0.5 micrograms/kg/min (0.01 mL/kg/hr)) under such condition.
Interventions/Control_2	Each subject will be administered saline intravenously at a rate of 0.06 mL/kg/hr just after anesthetic induction. Heart rate should be maintained at a level between 50 and 80 bpm. The infusion rate of saline can be increased by a rate of 0.02 mL/kg/hr when heart rate is over 80 bpm for 15 or 20 minutes and decreased by a rate of 0.01-0.02 mL/kg/hr when the heart rate obviously tend to decrease even within the target heart rate (50-80 bpm). Infusion of saline should be maintained within a rate of 0.01-0.4 mL/kg/hr for 24 hours. Medical treatment using atropine or ephedrine etc. or pacing therapy will be performed when heart rate is under 50 bpm, however infusion of saline has to be maintained with minimum rate (0.01 mL/kg/hr) under such condition.
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	20 years-old <=
Age-upper limit	85 years-old >
Gender	Male and Female
Key inclusion criteria	1) Patients with written informed consent 2) Patients aged from 20 to 85 years old 3) Patients who are going to have first CABG surgery
Key exclusion criteria	1) Patients with acute myocardial infarction occurred within 3 days after getting informed consent 2) Patients with history of atrial fibrillation or atrial flutter (including paroxysmal atrial fibrillation or atrial flutter) 3) Patients who will have any emergency operations within 24 hours after the hospital visits 4) Patients with cardiac shock 5) Patients with diabetic keto-acidosis or metabolic acidosis 6) Patients with bradyarrhythmias (sick sinus syndrome or second or third degree atrioventricular block) 7) Patients with pulmonary arterial hypertension complicating right heart failure 8) Patients with severe heart failure (NYHA functional classification is greater than grade three or ejection fraction is less than 35%) 9) Patients or suspected persons with untreated pheochromocytoma 10) Pregnant women or women with breast-feeding or patients who have possibilities of pregnancy 11) Patients with bronchial asthma or chronic lung diseases 12) Patients with past history of drug hypersensitivity against Landiolol 13) Patients who are judged by the investigators to be inappropriate for this study
Target sample size	520

Research contact person
Name of lead principal investigator	Atsuhiro Sakamoto
Organization	Nippon Medical School
Division name	Department of Anesthesiology
Address	1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602 JAPAN
TEL
Email

Public contact
Name of contact person	Atsuhiro Sakamoto
Organization	Nippon Medical School
Division name	Department of Anesthesiology
Address	1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602 JAPAN
TEL	03-3822-2131
Homepage URL	http://jlknight.net/
Email

Sponsor
Institute	The Society of Clinical Peri-operative Circulation Management
Institute
Department

Funding Source
Organization	Japan Heart Foundation
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization

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

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

Other administrative information
Date of disclosure of the study information	2013 Year 05 Month 07 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 04 Month 16 Day
Anticipated trial start date	2013 Year 09 Month 09 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2013 Year 05 Month 07 Day
Last modified on	2018 Year 10 Month 05 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012416