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

Heart Valve Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01802619
• Other study ID #: 20121025-8
• Secondary ID: 81000232
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 25, 2013
• Last updated: February 10, 2018
• Start date: August 2013
• Est. completion date: June 2016

Study information

• Verified date: February 2018
• Source: Xijing Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 217
• Est. completion date: June 2016
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Valve Replacement Complication
• Heart Valve Diseases
• Heart; Complications, Valve, Prosthesis
• Renal Insufficiency

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Xijing Hospital	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	In-hospital stay	It is the length of hospital stay	Normally within 30 days, when patients was discharged from ICU
Other	ICU-stay	It is the length of stay in ICU	Normally within 30 days, when patients was discharged from ICU
Other	Incidence of prolonged ventilation	Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours	During hospital stay, normally within 30 days
Primary	acute kidney injury	acute kidney injury was defined by the KDIGO criteria	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
Secondary	Chronic kidney disease	defined as eGFR<60 mL/min/1.73m2	at 30 days, 90 days, and 1 year following ICU admission
Secondary	Loss of 25% of eGFR compared to baseline	Loss of 25% of eGFR compared to baseline	at 30 days, 90 days, and 1 year following ICU admission
Secondary	Major adverse kidney events (MAKE)	a composite outcome of loss of 25% of eGFR from baseline, end stage renal disease requiring a continuous renal replacement therapy and mortality.	at 30 days, 90 days, and 1 year following ICU admission
Secondary	Renal Replacement Therapy	the incidence of need for Renal Replacement Therapy	at 30 days, 90 days, and 1 year following ICU admission
Secondary	Incidence of nonfatal stroke and nonfatal myocardial infarction.	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.	at 30 days, 90 days, and 1 year following ICU admission
Secondary	Quality of life	The quality of life will be evaluated by the Katz Index of In dependence in Activities of Daily living	at 30 days, 90 days, and 1 year following ICU admission
Secondary	overall mortality	all cause mortality	at 30 days, 90 days, and 1 year following ICU admission