NOinCPB: Nitric Oxide-mediated Cardioprotection During Cardiac Surgery With Cardiopulmonary Bypass

Sponsor

Tomsk National Research Medical Center of the Russian Academy of Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT03500783

Collaborator

(none)

Enrollment

Arms

18.6

Actual Duration (Months)

Study Details

Study Description

Brief Summary

This prospective randomized study elucidates the effects of exogenous nitric oxide delivered to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass graft surgery with cardiopulmonary bypass.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Coronary Artery Bypass Cardiopulmonary Bypass Nitric Oxide Reperfusion Injury, Myocardial	Drug: Nitric Oxide Other: Standard CPB	Phase 1/Phase 2

Detailed Description

The aim of this study is to investigate the effects of exogenous nitric oxide (NO) delivered to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB). A total of 60 patients with ischemic heart disease referred for CABG with CPB are included in prospective randomized study. Patients are randomized to receive standard treatment or surgery based on modified CPB protocol. According to modified protocol, 40-ppm NO is supplied to the CPB circuit during CABG. The primary endpoints are changes in cardiac troponin I (cTnI) levels at 6, 24, and 48 hours after surgery compared with baseline. The secondary end points are the changes in the levels of creatine kinase-muscle/brain (CK-MB) compared with baseline and vasoactive inotropic score (VIS) at 6, 24, and 48 hours. NO supplied to the CPB circuit exertes cardioprotective effect. Changes in cTnI, CK-MB, and VIS are considered indictors of the presence or absence of cardioprotective action of NO supplied to the CPB circuit.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single-center prospective, randomized, placebo-controlled studySingle-center prospective, randomized, placebo-controlled study

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

Trial participants, data analysts, and report writers are blinded.

Primary Purpose:

Prevention

Official Title:

Nitric Oxide-mediated Cardioprotection During Cardiac Surgery With Cardiopulmonary Bypass

Actual Study Start Date :

May 15, 2015

Actual Primary Completion Date :

Nov 30, 2016

Actual Study Completion Date :

Nov 30, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nitric Oxide Patients of this group receive treatment with exogenous gaseous nitric oxide supplied directly to the oxygenator in the cardiopulmonary bypass circuit during coronary artery bypass grafting for coronary artery disease.	Drug: Nitric Oxide 40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during coronary artery bypass grafting.
Placebo Comparator: Standard CPB Patients of this group receive sham-treatment without supplying nitric oxide to the cardiopulmonary bypass circuit during coronary artery bypass grafting for coronary artery disease. Considering dilution of nitric oxide at a high ratio of 1 to 25,000 in the gas mixture of the cardiopulmonary bypass circuit (CPB), no addition of any inert gas to the CPB circuit is required in sham-treatment group.	Other: Standard CPB Standard protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit Other Names: Cardiopulmonary bypass

Arm

Intervention/Treatment

Experimental: Nitric Oxide

Patients of this group receive treatment with exogenous gaseous nitric oxide supplied directly to the oxygenator in the cardiopulmonary bypass circuit during coronary artery bypass grafting for coronary artery disease.

Drug: Nitric Oxide

40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during coronary artery bypass grafting.

Placebo Comparator: Standard CPB

Patients of this group receive sham-treatment without supplying nitric oxide to the cardiopulmonary bypass circuit during coronary artery bypass grafting for coronary artery disease. Considering dilution of nitric oxide at a high ratio of 1 to 25,000 in the gas mixture of the cardiopulmonary bypass circuit (CPB), no addition of any inert gas to the CPB circuit is required in sham-treatment group.

Other: Standard CPB

Standard protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit

Other Names:

Cardiopulmonary bypass

Outcome Measures

Primary Outcome Measures

Cardiac troponin I change measure (cTnI) [48 hours (with intermediate measurements at 6 and 24 hours)]
Changes in the plasma level of cTnI (ng/mL) relative to the baseline value are measured at 6, 24, and 48 hours after surgery.

Secondary Outcome Measures

Creatine kinase-muscle/brain change measure (CK-MB) [48 hours (with intermediate measurements at 6 and 24 hours)]
Changes in the plasma level of CK-MB (U/L) relative to the baseline value are measured at 6, 24, and 48 hours after surgery.
Vasoactive inotropic score measure (VIS) [48 hours (with intermediate measurements at 6 and 24 hours)]
Vasoactive inotropic score (VIS) is assessed at 6, 24, and 48 hours after surgery. VIS is calculated as follows: (dobutamine μg/kg/min × 1 + dopamine μg/kg/min × 1 + milrinone μg/kg/min × 10) + 100 × (adrenalin μg/kg/min + noradrenaline μg/kg/min + vasopressin μg/kg/min).

Eligibility Criteria

Criteria

Ages Eligible for Study:

56 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Coronary artery disease requiring coronary artery bypass grafting with the cardiopulmonary bypass.

Exclusion Criteria:

Non-elective surgery, age over 70 years, left ventricular ejection fraction less than 35%, history of myocardial infarction within three months prior to surgery, chronic atrial fibrillation, diabetes mellitus, and the elevated levels of cardiac specific markers within 12 h prior to the intervention.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Tomsk National Research Medical Center of the Russian Academy of Sciences

Investigators

Study Director: Sergey V Popov, MD, Tomsk NRMC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nikolay Kamenshchikov, Principal Investigator, Physician Anesthesiologist, Tomsk National Research Medical Center of the Russian Academy of Sciences

ClinicalTrials.gov Identifier:

NCT03500783

Other Study ID Numbers:

NOinCPB

First Posted:

Apr 18, 2018

Last Update Posted:

Jul 5, 2019

Last Verified:

Jul 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Nikolay Kamenshchikov, Principal Investigator, Physician Anesthesiologist, Tomsk National Research Medical Center of the Russian Academy of Sciences

Cardioprotection

Ischemia-reperfusion injury

Nitric oxide

Cardiopulmonary bypass

Coronary artery bypass grafting

Additional relevant MeSH terms:

Coronary Artery Disease

Reperfusion Injury

Myocardial Reperfusion Injury

Nitric Oxide

Study Results

No Results Posted as of Jul 5, 2019