UMIN-CTR Clinical Trial

Public title

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

Acronym

JL-KNIGHT study II (Japan Landiolol-Kicking off the novel investigation for gold standard heart study II)

Scientific Title

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

Scientific Title:Acronym

JL-KNIGHT study II (Japan Landiolol-Kicking off the novel investigation for gold standard heart study II)

Region

Japan

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

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

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

Study type

Interventional

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

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Atsuhiro Sakamoto

Organization

Nippon Medical School

Division name

Department of Anesthesiology

Zip code

Address

1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602 JAPAN

TEL

Email

Name of contact person

1st name
Middle name
Last name	Atsuhiro Sakamoto

Organization

Nippon Medical School

Division name

Department of Anesthesiology

Zip code

Address

1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602 JAPAN

TEL

03-3822-2131

Homepage URL

http://jlknight.net/

Email

Institute

The Society of Clinical Peri-operative Circulation Management

Institute

Department

Personal name

Organization

Japan Heart Foundation

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

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

Date of disclosure of the study information

2013

Year

05

Month

07

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

2013

Year

04

Month

16

Day

Date of IRB

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

Other related information

Registered date

2013

Year

05

Month

07

Day

Last modified on

2018

Year

10

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012416