Nitric Oxide During CPB to Reduce AKI in Neonates

A Prospective Randomized Controlled Trial of Supplemental Nitric Oxide During Cardiopulmonary Bypass to Reduce Acute Kidney Injury After Cardiac Surgery

This is a prospective, randomized, double-blind, placebo-controlled pilot study to investigate whether supplemental Nitric Oxide (NO) gas delivered during cardiac surgery with cardiopulmonary bypass (CPB) reduces the incidence and impact of acute kidney injury (AKI) in neonates undergoing surgery for congenital heart disease (CHD), when compared to placebo gas

Study Overview

• Status: Withdrawn
• Conditions: Acute Kidney Injury; Congenital Heart Disease
• Intervention / Treatment: Drug: NO gas delivered during cardiac surgery; Other: placebo gas delivered during cardiac surgery

Detailed Description

Screening: All patients undergoing either elective or emergency cardiac surgery will be screened against the eligibility criteria.

Research Sample Collection: Blood and urine will be collected for the first 48 hours admission and analyzed. The specific time points for these parameters will be: 2 hours, 6 hours, 12 hours 24 hours, and 48 hours post admission. Blood and urine parameters will also be collected as a baseline pre-operative. Patient outcomes will be captured for 30 days post operatively.

Research Data Collection: Baseline information will be collected. Other research related variables collected during the surgical intervention and bypass. Additional information will be collected 2 hours, 6 hours, 12 hours, 24 hours, and 48 hours after admission as well as outcomes 30 days after the procedure.

Participants will be randomly allocated to the NO or control group in a 1:1 ratio.

This study is investigating a possible protective role for NO gas administration during bypass on the subsequent development of AKI. NO is typically delivered via large, stand-alone cylinders that are placed at the bedside (or adjacent to the patient) and is set up by respiratory therapists. In this research study, the study gas (NO or placebo) will be delivered directly into the bypass circuit at a constant gas flow. The placebo gas in this study will be 21% (or atmospheric) oxygen, and will appear to all members of the clinical and research teams (with the exception of the respiratory therapist responsible for setting it up) indistinguishable from NO, rendering this a double-blind study for the patient (or caregiver) and the investigators. This minimizes any possibility of bias in the study.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: </= 30 days
• Gestational age: 38 weeks
• Diagnosis: Congenital Heart Disease (CHD)
• Planned surgery to include cardiopulmonary bypass (CPB )for underlying CHD
• Consent of parent/guardian

Exclusion Criteria:

• Currently receiving or has received inhaled nitric oxide (NO) or other nitrogen donors such as sildenafil or nitroprusside
• Pre-existing acute kidney injury (AKI) as per the AKIN criteria;
• Cardiac arrest within one week prior consent;
• Prior cardiac surgery with CPB procedure;
• Prior history of Extra Corporeal Membrane Oxygenation (ECMO)
• Use of another investigational drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group	Other: placebo gas delivered during cardiac surgery; placebo blended into the fresh gas flow of the CPB oxygenator via the INOMax delivery system. The placebo gas in this study will be 21% (or atmospheric) oxygen.
Experimental: NO Group	Drug: NO gas delivered during cardiac surgery; intra-operative NO gas at 20ppm blended into the fresh gas flow of the CPB oxygenator via the INOMax delivery system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NGAL level	1 of 2 biomarkers to determine acute kidney injury (AKI)	48 hours
Cystatin-C level	2 of 2 biomarkers to determine acute kidney injury (AKI)	48 hours

Collaborators and Investigators

• Sponsor: Fabio Savorgnan
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Fabio Savorgnan, MD, Texas Children's Hospital / Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): December 1, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: cardiac surgery; Congenital Heart Disease; infant; Acute Kidney Injury; CHD; neonate; Cardiopulmonary bypass; nitric oxide; NO; CPB; AKI; gestational age
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Renal Insufficiency; Cardiovascular Abnormalities; Heart Diseases; Acute Kidney Injury; Heart Defects, Congenital
• Other Study ID Numbers: H-44435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No