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Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass.

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ClinicalTrials.gov Identifier: NCT01802619
Recruitment Status : Completed
First Posted : March 1, 2013
Last Update Posted : February 13, 2018
Sponsor:
Information provided by (Responsible Party):
chonglei, Xijing Hospital

February 25, 2013
March 1, 2013
February 13, 2018
August 2013
June 2015   (Final data collection date for primary outcome measure)
acute kidney injury [ Time Frame: an increase of serum creatinine by 50% within 7 days after surgery, or an increase of serum creatinine by 0.3 mg/dl within 2 days after surgery ]
acute kidney injury was defined by the KDIGO criteria
acute renal failure [ Time Frame: within 28 days after the procedure ]
Renal failure will be defined according to the RIFLE/ AKIN criteria .
Complete list of historical versions of study NCT01802619 on ClinicalTrials.gov Archive Site
  • Chronic kidney disease [ Time Frame: at 30 days, 90 days, and 1 year following ICU admission ]
    defined as eGFR<60 mL/min/1.73m2
  • Loss of 25% of eGFR compared to baseline [ Time Frame: at 30 days, 90 days, and 1 year following ICU admission ]
    Loss of 25% of eGFR compared to baseline
  • Major adverse kidney events (MAKE) [ Time Frame: at 30 days, 90 days, and 1 year following ICU admission ]
    a composite outcome of loss of 25% of eGFR from baseline, end stage renal disease requiring a continuous renal replacement therapy and mortality.
  • Renal Replacement Therapy [ Time Frame: at 30 days, 90 days, and 1 year following ICU admission ]
    the incidence of need for Renal Replacement Therapy
  • Incidence of nonfatal stroke and nonfatal myocardial infarction. [ Time Frame: at 30 days, 90 days, and 1 year following ICU admission ]

    Nonfatal stroke will be assessed by the NIH Stroke Scale at baseline before surgery and at 28 days, 60 days, 90 days and 1 year after surgery.

    Nonfatal myocardial infarction is defined by the third universal definition of MI released in 2012 by the ESC/ACCF/AHA/WHF.

  • Quality of life [ Time Frame: at 30 days, 90 days, and 1 year following ICU admission ]
    The quality of life will be evaluated by the Katz Index of In dependence in Activities of Daily living
  • overall mortality [ Time Frame: at 30 days, 90 days, and 1 year following ICU admission ]
    all cause mortality
  • acute renal failure [ Time Frame: at 60 days, 90 days and 1 year ]
  • Incidence of nofatal stroke and nonfatal myocardial infarction. [ Time Frame: at 28 days, 60 days, 90 days and 1 year ]

    Nonfatal stroke will be assesed by the NIH Stroke Scale at baseline before surgery and at 28 days, 60 days, 90 days and 1 year after surgery.

    Nonfatal myocardial infarction is defined by the third universal definition of MI released in 2012 by the ESC/ACCF/AHA/WHF.

  • Quality of life [ Time Frame: at 28 days, 60 days, 90 days and 1 year ]
    The quality of life will be evaluated by the Katz Index of In dependence in Activities of Daily living
  • overall mortality [ Time Frame: at 28 days, 60 days, 90 days and 1 year ]
  • In-hospital stay [ Time Frame: Normally within 30 days, when patients was discharged from ICU ]
    It is the length of hospital stay
  • ICU-stay [ Time Frame: Normally within 30 days, when patients was discharged from ICU ]
    It is the length of stay in ICU
  • Incidence of prolonged ventilation [ Time Frame: During hospital stay, normally within 30 days ]
    Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours
  • In-hospital stay [ Time Frame: at 28 days ]
    It is the length of hospital stay
  • ICU-stay [ Time Frame: at 28 days ]
    It is the length of stay in ICU
  • Incidence of prolonged ventilation [ Time Frame: at 28 days ]
    Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours
 
Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass.
Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.
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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
  • Heart Valve Diseases
  • Heart; Complications, Valve, Prosthesis
  • Cardiac Valve Replacement Complication
  • Other: 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.
  • Other: 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.
  • Placebo Comparator: inhaled nitrogen
    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.
    Intervention: Other: inhaled Nitrogen
  • Experimental: inhaled nitric oxide
    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.
    Intervention: Other: inhaled nitric oxide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
217
314
June 2016
June 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
China
 
 
NCT01802619
20121025-8
81000232 ( Other Grant/Funding Number: National Natural Science Foundation of China )
Yes
Not Provided
Not Provided
chonglei, Xijing Hospital
Xijing Hospital
Not Provided
Study Chair: lize Xiong, M.D.,Ph.D. Xijing Hospital
Xijing Hospital
February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP