Clinical trial NCT01348971: Coronary Artery Bypass and Nitrate Oral Supplementation
Official title: Effects of Oral Nitrate During Coronary Artery Bypass Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease
Keywords: sodium nitrate
coronary artery bypass surgery
ischemia-reperfusion
myocardial injury
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2011-05-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine whether oral sodium nitrate administration prior to coronary artery bypass surgery can reduce perioperative levels of troponin T. In addition, plasma and urine surrogate markers of renal, hepatic and brain injury will be monitored.

Detailed description: Nitric oxide (NO) is an important mediator in the cardiovascular system and has been shown to have protective properties in ischemia-reperfusion injury. Inorganic nitrate, an oxidation product from endogenous NO production and also a constituent in green leafy vegetables, can be recycled, via nitrite, back to bioactive NO in the body. Recent research has shown beneficial effects of nitrate and nitrite in animal models of myocardial ischemia-reperfusion injury. Moreover, dietary nitrate reduces blood pressure and oxygen cost during exercise in humans.

During coronary bypass surgery the heart undergoes ischemia-reperfusion injury and troponin T is most often released from the myocardium. The aim of the present study is to investigate if preoperative inorganic nitrate, in doses easily achievable from the diet, can affect troponin T release as well as other surrogate markers of injury to the liver, kidneys and the brain. In addition, plasma and urine samples will be collected for markers of oxidative stress and inflammation (sCRP and cytokines). Patients planned for bypass surgery who give their written informed consent will, the night before surgery, get a standardized, low-nitrate meal where after they receive sodium nitrate on two occasions preoperatively; the night before and in the morning before surgery. Plasma and urine samples will be collected at various time points up to 72 hours after surgery.

Eligibility criteria: Inclusion Criteria:

* Patients undergoing coronary artery bypass surgery
* Over 18 years of age

Exclusion Criteria:

* Over 80 years of age
* Pregnancy
* Reoperation
* Intended heart valve or additional surgery
* Angina or troponin release above 45 nmol/L \< 48 hours before surgery
* Medication with organic nitrates/nitrites \< 24 hours before surgery
* Medication with glibenclamide or corticosteroids
* Significant renal, pulmonary or hepatic disease

Primary outcomes:
measure: Troponin T release over the perioperative 72-hour period.
timeFrame: 72 hours
Secondary outcomes:
measure: Troponin T release over the perioperative 24-hour period.
timeFrame: 24 h
measure: Creatinine kinase myocardial fraction (CKMB) release over the perioperative 72-hour period
timeFrame: 72 hours
measure: Creatinine kinase myocardial fraction (CKMB) release over the perioperative 24-hour period
timeFrame: 24 hours
measure: Pro Brain natriuretic peptide (proBNP) release over the perioperative 72-hour period.
timeFrame: 72 hours
measure: Aspartate aminotransferase (AST) release over the perioperative 72-hour period.
timeFrame: 72 hours
measure: Alaninaminotransferas (ALAT) release over the perioperative 72-hour period.
timeFrame: 72 hours
measure: Alkaline phosphatase (ALP) release over the perioperative 72-hour period.
timeFrame: 72 hours
measure: Bilirubin release over the perioperative 72-hour period
timeFrame: 72 hours
measure: Creatinine release over the perioperative 72-hour period
timeFrame: 72 h
measure: Cystatin C release over the perioperative 72-hour period
timeFrame: 72
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska Institutet
name: Eddie T Weitzberg, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Eriksson KE, Eidhagen F, Liska J, Franco-Cereceda A, Lundberg JO, Weitzberg E. Effects of inorganic nitrate on ischaemia-reperfusion injury after coronary artery bypass surgery: a randomised controlled trial. Br J Anaesth. 2021 Oct;127(4):547-555. doi: 10.1016/j.bja.2021.06.046. Epub 2021 Aug 14.