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
  Purpose

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.


Condition Intervention Phase
Heart Valve Diseases
Heart; Complications, Valve, Prosthesis
Cardiac Valve Replacement Complication
Other: inhaled nitric oxide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.

Resource links provided by NLM:


Further study details as provided by Xijing Hospital:

Primary Outcome Measures:
  • 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 .


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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


Estimated Enrollment: 314
Study Start Date: August 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802619

Contacts
Contact: Chong Lei, M.D., Ph.D., 86-18629011362 leichongbb@gmail.com
Contact: Hui Zhang, M.D., 86-15991700956 zhanghuia309@163.com

Locations
China, Shaanxi
Xijing Hospital Recruiting
Xi'an, Shaanxi, China, 710032
Contact: Chong Lei, M.D., Ph.D.    86-18629011362    leichongbb@gmail.com   
Principal Investigator: Chong Lei, M.D., Ph.D,         
Sponsors and Collaborators
Xijing Hospital
Investigators
Study Chair: lize Xiong, M.D.,Ph.D. Xijing Hospital
  More Information

No publications provided

Responsible Party: Xijing Hospital
ClinicalTrials.gov Identifier: NCT01802619     History of Changes
Other Study ID Numbers: 20121025-8, 81000232
Study First Received: February 25, 2013
Last Updated: August 18, 2014
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Renal Insufficiency
Heart Valve Diseases
Kidney Diseases
Urologic Diseases
Heart Diseases
Cardiovascular Diseases
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Gasotransmitters
Protective Agents

ClinicalTrials.gov processed this record on September 18, 2014