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

Phase 2

Withdrawn

• Conditions: Congenital Heart Disease; Acute Kidney Injury
• Interventions: Drug: gases Nitric Oxide (gNO)

• Registration Number: NCT04259684
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-19
• Status Verified: 2019-10
• Study Start: 2019-10-20
• Primary Completion: 2019-10-20
• Study Completion: 2019-10-20
• Study First Submitted QC: 2020-02-05
• Last Update Submitted: 2020-02-05
• Study First Posted: 2020-02-06
• Last Update Posted: 2020-02-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
gNO Group	gases Nitric Oxide (gNO)	Participants in the treatment group will receive gNO added to the oxygenator gas flow at 20 ppm throughout the duration of cardiopulmonary bypass.

Primary Outcome Measures

Name	Time	Method
Glomerular Filtration Rate	up to 72 hours postoperative	Postoperative glomerular filtration rate (GFR) measured using serum cystatin C.
Acute Kidney Injury	up to 72 hours postoperative	Occurrence of acute kidney defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification (employing both serum creatinine and urine output criteria).

Secondary Outcome Measures

Name	Time	Method
Closed sternum days	up to 2 weeks from postoperative CICU admission to discharge	days
Length of cardiac intensive care unit (CICU) stay	up to 2 weeksfrom admission to CICU to discharge from CICU	days
Length of hospital stay	up to 30 days from hospital admission to discharge	days
Low cardiac output syndrome (LCOS)	up to 48 hours postoperative	Occurence of low cardiac output syndrome (LCOS) defined as any of the following at any time during the first 48 hours postoperative: 1. Lactate \>6mmol/l and central venous saturation (ScvO2) \<60% (or SaO2-ScvO2 difference greater than 35% in a single ventricle),; 2. Vasoactive inotropic score (VIS)24 ≥ 10,; 3. Extracorporeal Membrane Oxygenation (ECMO).
Structural Kidney Injury	up to 72 hours postoperative	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.
Duration of mechanical ventilation	up to 2 weeks from admission to CICU to extubation	hours/days
Use of postoperative inhaled Nitric Oxide (iNO)	up to two weeks from CICU admission to discharge	yes/no, indication, dose
ECMO free days	up to 2 weeks after surgery to CICU discharge	Extracorporeal Membrane Oxygenation free days
Time to negative fluid balance	up to 2 weeks from CICU admission to outcome reached	hours/days
Urine Output	up to two weeks from CICU admission to discharge	ml
Cardiac arrest	up to two weeks from CICU admission to discharge	yes/no
Inotrope free days	up to 30 days after surgery to CICU discharge	days
Use of peritoneal dialysis	up to two weeks from CICU admission to discharge	yes/no