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

NCT04259684 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CIN001-gNO to prevent AKI
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Kidney Injury; Congenital Heart Disease

Outcome Measures

Primary Outcomes (2)

• 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

• Glomerular Filtration Rate

  Postoperative glomerular filtration rate (GFR) measured using serum cystatin C.

  up to 72 hours postoperative

Secondary Outcomes (13)

• Structural Kidney Injury

  up to 72 hours postoperative

• Low cardiac output syndrome (LCOS)

  up to 48 hours postoperative

• Duration of mechanical ventilation

  up to 2 weeks from admission to CICU to extubation

• Length of cardiac intensive care unit (CICU) stay

  up to 2 weeksfrom admission to CICU to discharge from CICU

• Length of hospital stay

  up to 30 days from hospital admission to discharge

Study Arms (2)

gNO Group

EXPERIMENTAL

Participants in the treatment group will receive gNO added to the oxygenator gas flow at 20 ppm throughout the duration of cardiopulmonary bypass.

Drug: gases Nitric Oxide (gNO)

Control Group

NO INTERVENTION

Participants in the control group will receive standard conduction of cardiopulmonary bypass.

Interventions

gases Nitric Oxide (gNO) DRUG

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.

gNO Group

Eligibility Criteria

• Age: Up to 31 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

MeSH Terms

Conditions

Acute Kidney Injury; Heart Defects, Congenital

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each of the 40 participants will be stratified based on type of lesion (single ventricle vs. biventricular lesions) and block randomized into 1 of 2 study arms: treatment arm (receiving intraoperative administration of 20 ppm of gNO to the oxygenator of the CPB circuit) and control arm (standard CPB conduct).

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: February 6, 2020
• Study Start: October 20, 2019
• Primary Completion: October 20, 2019
• Study Completion: October 20, 2019
• Last Updated: February 6, 2020

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share