Overview

This trial is active, not recruiting.

Conditions heart valve diseases, heart; complications, valve, prosthesis, cardiac valve replacement complication
Treatments inhaled nitric oxide, inhaled nitrogen
Phase phase 1/phase 2
Sponsor Xijing Hospital
Start date August 2013
End date June 2015
Trial size 212 participants
Trial identifier NCT01802619, 20121025-8, 81000232

Summary

Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose prevention
Arm
(Placebo Comparator)
Using an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, pure nitrogen (placebo) is mixed with pure O2 or air. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the NO is delivered through the inspiratory limb of the anesthetic or ventilator circuit.
inhaled nitrogen
Standard gas including nitrogen (the vehicle of the Nitric oxide) administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, inhaled gases will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.
(Experimental)
Using an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, 800 ppm NO gas is mixed with pure O2 or air to obtain a final concentration of 80 ppm NO. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the gas is delivered through the inspiratory limb of the anesthetic or ventilator circuit. NO, NO2 and O2 and methemoglobin levels are monitored by an unblinded observer.
inhaled nitric oxide
Nitric oxide administration will commence at the onset of CPB and last for 24 hours. At the end of 24 hours, inhaled NO will be weaned and discontinued while carefully monitoring hemodynamics for a period of 2-4 hours.

Primary Outcomes

Measure
acute renal failure
time frame: within 28 days after the procedure

Secondary Outcomes

Measure
acute renal failure
time frame: at 60 days, 90 days and 1 year
Incidence of nonfatal stroke and nonfatal myocardial infarction.
time frame: at 28 days, 60 days, 90 days and 1 year
Quality of life
time frame: at 28 days, 60 days, 90 days and 1 year
overall mortality
time frame: at 28 days, 60 days, 90 days and 1 year

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Provide written informed consent - Are > 18 years of age - Elective cardiac or aortic surgery with CPB, when the surgeon plans double valve replacement. - Stable pre-operative renal function, without dialysis. Exclusion Criteria: - Emergent cardiac surgery - Life expectancy < 1 year - Hemodynamic instability as defined by a systolic blood pressure <90 mmHg - Administration of ≥1 Packed Red Blood Cell transfusion in the week before surgery - X-ray contrast infusion less than 1 week before surgery - Anticipate administration of nephrotoxic agents, such as hydroxyethyl starch - Evidence of intravascular or extravascular hemolysis

Additional Information

Official title Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.
Description Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging. There are three possible beneficial mechanisms of delivering NO: 1. Nitric oxide reduces ischemia-reperfusion injury (such as in acute myocardial infarction, stroke, and acute tubular necrosis). 2. Nitric oxide has anti-inflammatory properties. As antioxidants, exogenous NO may reduce injury by counteracting the cytotoxic effects of reactive oxygen species, modulating leukocyte recruitment, edema formation and tissue disruption. 3. Exogenous nitric oxide prevents noxious effects of hemolysis-associated NO dysregulation. During hemolysis, nitric oxide gas oxidized of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous endothelium NO scavenging by cell-free Hb. NO depletion during hemolysis and its sequelae. The release of plasma free Hb (with Fe2+ iron) by hemolysis avidly scavenges nitric oxide (NO) by the dioxygenation reaction. Elevated plasma ferrous Hb levels can induce a "NO deficiency" state. Reduced vascular nitric oxide levels can contribute to vasoconstriction, inflammation, and thrombosis, potentially contributing to systemic endothelial dysfunction after cardiac surgery with CPB.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by Xijing Hospital.