Clinical trial NCT01802619: Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass.
Official title: Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass: A Double Blind Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Heart Valve Diseases
Heart; Complications, Valve, Prosthesis
Cardiac Valve Replacement Complication
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2013-03-01
Enrollment: 217
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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 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
* Anticipate administration of nephrotoxic agents, such as hydroxyethyl starch
* Evidence of intravascular or extravascular hemolysis

Primary outcomes:
measure: acute kidney injury
timeFrame: 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 outcomes:
measure: Chronic kidney disease
timeFrame: at 30 days, 90 days, and 1 year following ICU admission
measure: Loss of 25% of eGFR compared to baseline
timeFrame: at 30 days, 90 days, and 1 year following ICU admission
measure: Major adverse kidney events (MAKE)
timeFrame: at 30 days, 90 days, and 1 year following ICU admission
measure: Renal Replacement Therapy
timeFrame: at 30 days, 90 days, and 1 year following ICU admission
measure: Incidence of nonfatal stroke and nonfatal myocardial infarction.
timeFrame: at 30 days, 90 days, and 1 year following ICU admission
measure: Quality of life
timeFrame: at 30 days, 90 days, and 1 year following ICU admission
measure: overall mortality
timeFrame: at 30 days, 90 days, and 1 year following ICU admission
Other outcomes:
measure: In-hospital stay
timeFrame: Normally within 30 days, when patients was discharged from ICU
measure: ICU-stay
timeFrame: Normally within 30 days, when patients was discharged from ICU
measure: Incidence of prolonged ventilation
timeFrame: During hospital stay, normally within 30 days
Locations:
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
Study officials:
affiliation: Xijing Hospital
name: lize Xiong, M.D.,Ph.D.
role: STUDY_CHAIR
References:
citation: Hu J, Rezoagli E, Zadek F, Bittner EA, Lei C, Berra L. Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial. Anesth Analg. 2021 Jun 1;132(6):1548-1558. doi: 10.1213/ANE.0000000000005381.
citation: Lei C, Berra L, Rezoagli E, Yu B, Dong H, Yu S, Hou L, Chen M, Chen W, Wang H, Zheng Q, Shen J, Jin Z, Chen T, Zhao R, Christie E, Sabbisetti VS, Nordio F, Bonventre JV, Xiong L, Zapol WM. Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery. Am J Respir Crit Care Med. 2018 Nov 15;198(10):1279-1287. doi: 10.1164/rccm.201710-2150OC.