Nitric Oxide During Cardiopulmonary Bypass in Neonates to Reduce Risk of Acute Kidney Injury

Acute Kidney Injury Clinical Trial

Official title:

Efficacy of Nitric Oxide Administration During Cardiopulmonary Bypass in Neonates at Reducing the Risk of Acute Kidney Injury: a Preliminary Double-blind Randomized Controlled Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04259684
• Other study ID #: CIN001-gNO to prevent AKI
• Status: Withdrawn
• Phase: Phase 2/Phase 3
• Start date: October 20, 2019
• Est. completion date: October 20, 2019

Study information

• Verified date: October 2019
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute kidney injury following cardiac surgery for congenital heart defects in children is a major cause of both short- and long-term morbidity and mortality, affecting up to 60% of high risk patients. Despite effort, to date, no successful therapeutic agent has gained widespread success in preventing this postoperative decline in renal function. Based on preliminary data available in the literature, we hypothesize that nitric oxide (gNO), administered during cardiopulmonary bypass (CPB), may reduce the risk of acute kidney injury (AKI) via mechanisms of reduced inflammation and vasodilation. In this pilot study, 40 neonates undergoing cardiac surgery will be randomized to receive intraoperative administration of 20 ppm of nitric oxide to the oxygenator of the cardiopulmonary bypass circuit or standard CPB with no additional gas.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 20, 2019
• Est. primary completion date: October 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 31 Days

Eligibility

Inclusion Criteria:

• Neonates (=31 days) undergoing cardiac surgery with cardiopulmonary bypass for congenital heart disease

Exclusion Criteria:

• 1. Failure to obtain informed consent from parent/guardian,

• Clinical signs of preoperative persistent elevated pulmonary vascular resistance,

• Emergency surgery,

• Episode of cardiac arrest within 1 week before surgery,

• Recent treatment with steroids and/or a condition that may require treatment with steroids (excluding steroid administration specifically for CPB),

• Use of inhaled NO (iNO) immediately prior to surgery,

• Structural renal abnormalities by ultrasound,

• Preoperative AKI,

• Use of other investigational drugs,

• Weight less than <2.2 kg,

• Gestational age <36 weeks,

• Major extracardiac congenital anomalies.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Congenital Heart Disease
• Heart Diseases
• Wounds and Injuries

Intervention

Drug:
• gases Nitric Oxide (gNO)
Participants in the intervention group will receive gNO blended into the fresh gas flow of the cardiopulmonary bypass (CPB) oxygenator and maintained at 20 ppm via an Ikaria INO Max DSIR (Mallinckrodt Pharmaceuticals, St. Louis, Missouri, USA), with continuous sampling of NO and NO2 concentration from a port adjacent to the oxygenator. The gNO delivery will be initiated when the patient is on CPB and stopped once the patient comes off CPB.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Kidney Injury	Occurrence of acute kidney defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification (employing both serum creatinine and urine output criteria).	up to 72 hours postoperative
Primary	Glomerular Filtration Rate	Postoperative glomerular filtration rate (GFR) measured using serum cystatin C.	up to 72 hours postoperative
Secondary	Structural Kidney Injury	Assessed by measurement of urine biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) liver-type fatty acid-binding protein (L-FABP), and urinary nitrate.	up to 72 hours postoperative
Secondary	Low cardiac output syndrome (LCOS)	Occurence of low cardiac output syndrome (LCOS) defined as any of the following at any time during the first 48 hours postoperative: Lactate >6mmol/l and central venous saturation (ScvO2) <60% (or SaO2-ScvO2 difference greater than 35% in a single ventricle),; Vasoactive inotropic score (VIS)24 = 10,; Extracorporeal Membrane Oxygenation (ECMO).	up to 48 hours postoperative
Secondary	Duration of mechanical ventilation	hours/days	up to 2 weeks from admission to CICU to extubation
Secondary	Length of cardiac intensive care unit (CICU) stay	days	up to 2 weeksfrom admission to CICU to discharge from CICU
Secondary	Length of hospital stay	days	up to 30 days from hospital admission to discharge
Secondary	Inotrope free days	days	up to 30 days after surgery to CICU discharge
Secondary	ECMO free days	Extracorporeal Membrane Oxygenation free days	up to 2 weeks after surgery to CICU discharge
Secondary	Closed sternum days	days	up to 2 weeks from postoperative CICU admission to discharge
Secondary	Time to negative fluid balance	hours/days	up to 2 weeks from CICU admission to outcome reached
Secondary	Urine Output	ml	up to two weeks from CICU admission to discharge
Secondary	Use of peritoneal dialysis	yes/no	up to two weeks from CICU admission to discharge
Secondary	Cardiac arrest	yes/no	up to two weeks from CICU admission to discharge
Secondary	Use of postoperative inhaled Nitric Oxide (iNO)	yes/no, indication, dose	up to two weeks from CICU admission to discharge