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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Xijing Hospital
Sponsor:
Information provided by (Responsible Party):
Xijing Hospital
ClinicalTrials.gov Identifier:
NCT01802619
First received: February 25, 2013
Last updated: August 18, 2014
Last verified: August 2014

February 25, 2013
August 18, 2014
August 2013
August 2015   (final data collection date for primary outcome measure)
acute renal failure [ Time Frame: within 28 days after the procedure ] [ Designated as safety issue: No ]
Renal failure will be defined according to the RIFLE/ AKIN criteria .
Same as current
Complete list of historical versions of study NCT01802619 on ClinicalTrials.gov Archive Site
  • acute renal failure [ Time Frame: at 60 days, 90 days and 1 year ] [ Designated as safety issue: No ]
  • Incidence of nofatal stroke and nonfatal myocardial infarction. [ Time Frame: at 28 days, 60 days, 90 days and 1 year ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
Same as current
  • In-hospital stay [ Time Frame: at 28 days ] [ Designated as safety issue: No ]
    It is the length of hospital stay
  • ICU-stay [ Time Frame: at 28 days ] [ Designated as safety issue: No ]
    It is the length of stay in ICU
  • Incidence of prolonged ventilation [ Time Frame: at 28 days ] [ Designated as safety issue: No ]
    Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours
Same as current
 
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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.
  • 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.
  • 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.
 
Recruiting
314
August 2016
August 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
  • Evidence of intravascular or extravascular hemolysis
Both
18 Years and older
No
Contact: Chong Lei, M.D., Ph.D., 86-18629011362 leichongbb@gmail.com
Contact: Hui Zhang, M.D., 86-15991700956 zhanghuia309@163.com
China
 
NCT01802619
20121025-8, 81000232
Yes
Xijing Hospital
Xijing Hospital
Not Provided
Study Chair: lize Xiong, M.D.,Ph.D. Xijing Hospital
Xijing Hospital
August 2014

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