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Completed

NCT Number: NCT01802619

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

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.

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Key information

Conditions

Heart Valve Diseases Cardiac Valve Replacement Complication Cardiovascular Diseases Heart Diseases Heart; Complications, Valve, Prosthesis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Xijing Hospital

Xi'an, Shaanxi, 710032, China

About this study

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:

  • Nitric oxide reduces ischemia-reperfusion injury (such as in acute myocardial infarction, stroke, and acute tubular necrosis).
  • 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.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

inhaled nitric oxide

Other

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.

inhaled Nitrogen

Other

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.

Primary outcomes

  1. 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

Secondary outcomes

  1. Chronic kidney disease

    Time frame: at 30 days, 90 days, and 1 year following ICU admission

    defined as eGFR<60 mL/min/1.73m2

  2. 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

  3. 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.

  4. Renal Replacement Therapy

    Time frame: at 30 days, 90 days, and 1 year following ICU admission

    the incidence of need for Renal Replacement Therapy

  5. 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.

  6. 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

  7. overall mortality

    Time frame: at 30 days, 90 days, and 1 year following ICU admission

    all cause mortality

Other outcomes

  1. In-hospital stay

    Time frame: Normally within 30 days, when patients was discharged from ICU

    It is the length of hospital stay

  2. ICU-stay

    Time frame: Normally within 30 days, when patients was discharged from ICU

    It is the length of stay in ICU

  3. 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

Sponsors and collaborators

Lead sponsor

Xijing Hospital

Other

Registry information

Official study title

Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.

Important dates

Study start
2013
Primary completion
2015
Study completion
2016
First posted
Mar 1, 2013
Registry last updated
Feb 13, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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