Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period

NCT04452188 | Completed Results

• 2 other identifiers: HUM001750865UL1TR002240-05
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is studying the use of different levels of oxygen exposure during and after cardiopulmonary bypass in eligible infants to learn about its safety during heart surgery. In addition to having the various doses of oxygen, participants will also have blood samples, ultrasounds of the head, and brain wave patterns monitored. The hypotheses of this trial are:

• that there will be no difference with regards to adverse events between the infants in the normoxia group compared to the infants in the standard of care group
• there will be a significant difference in the measured partial pressure of oxygen (PaO2) values between the two treatment groups.
• the use of normoxia during cardiopulmonary bypass and in the immediate post-operative period will result in clinically significant decrease in oxidative stress as measured by thiobarbituric acid reactive substances (TBARS) after cardiac surgery

Conditions

Hypoplastic Left Heart Syndrome; Total Anomalous Pulmonary Venous Return; Truncus Arteriosus; Pulmonary Atresia With Ventricular Septal Defect; Transposition of the Great Arteries; Double Outlet Right Ventricle, Subpulmonary VSD; Tetralogy of Fallot; Double Outlet Right Ventricle With Subaortic Ventricular Septal Defect and Pulmonary Stenosis; Cardiopulmonary Bypass

Keywords

Open heart surgery

Outcome Measures

Primary Outcomes (6)

• Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS)

  Oxidative stress (OS) reflects an imbalance between the production and accumulation of reactive oxygen species. Oxidation of lipids leads to the generation of lipid peroxides which can be detected as Thiobarbituric acid reactive substances (TBARS). Thus, levels of serum TBARS were assessed in participants as indicators of OS. TBARS levels were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline pre-operative sample and described as a fold-of-change from baseline. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as TBARS level at each PO time point / TBARS at baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared.

  Up to 24 hours following surgery

• Rate of Observed Adverse Events Between the Two Groups

  The count of each of the adverse events within 30 days after the index cardiac surgery, listed here: mortality, cardiac arrest, need for mechanical circulatory support, seizures (clinical or subclinical based on EEG), and need for dialysis is presented below.

  30 days after surgery

• Post-operative Length of Stay

  Calculated as number of days in the hospital after surgery.

  30 days after surgery

• Days Alive and Out of the Intensive Care Unit (ICU) at 30 Days After Surgery

  This composite measure reflects the number of days alive and not admitted to the ICU. Non-survivors at day 30 were considered to have no ICU-free days.

  30 days after surgery

• Composite Outcome of Major Adverse Events

  The composite endpoint assessed in this study combines in-hospital mortality, cardiac arrest, ECMO, seizures, and dialysis and reflects the number of participants affected by one or more of these outcomes.

  30 days after surgery

• Global Rank Score

  Per NCT03229538, a composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. For this endpoint, each randomized patient will be assigned a rank based upon their most-severe outcome. Rank of 91= Post-operative length of stay \> 90 days, 92= Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93= Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94= Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95= Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96= Heart transplant (during hospitalization); 97= Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days. A lower score means a better outcome.

  30 days after surgery

Other Outcomes (3)

• Systemic Oxidative Stress Based on Protein Carbonyl Levels After Surgery

  Up to 24 hours after surgery

• Systemic Oxidative Stress Based on Total Antioxidant Capacity (TAC)

  Up to 24 hours after surgery

• Systemic Oxidative Stress Based on 8-Isoprostane Levels After Surgery

  Up to 24 hours after surgery

Study Arms (2)

Normoxia

EXPERIMENTAL

On bypass, goal PaO2 on cardiopulmonary bypass of 60-100 mm Hg using lower fraction of inspired oxygen (FiO2) (blended sweep gas) via oxygenator Post-bypass, goal of PaO2 \<100 mm Hg by anesthesia and in ICU via oxygen titration via mechanical ventilator for 24 hours post-op.

Other: Normoxia (with controlled re-oxygenation)

Standard of care

ACTIVE COMPARATOR

Frequent blood gases will be checked per protocol on bypass and correlated with the blood parameter monitoring system to maintain a PaO2 of 200-300 per standard practice

Other: Standard of care ventilation

Interventions

Normoxia (with controlled re-oxygenation) OTHER

Participants will receive lower levels of oxygen during surgery and after surgery on the ventilator. As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation with an FiO2 of 50% or less (unless clinically necessary) to achieve oxygen saturation and PaO2 goals that fit within the expected range for the participant's physiology: 1. Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%) 2. Two ventricle patients (PaO2: 60-100 and oxygen saturation \>92%)

Normoxia

Standard of care ventilation OTHER

As cardiopulmonary bypass is being weaned, anesthesia will initiate mechanical ventilation per standard protocols. Ventilation will be continued in the ICU and adjusted per standard goals per the intensivist.

Standard of care

Eligibility Criteria

• Age: Up to 29 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age less than 30 days of age at time of surgery with need for cardiopulmonary bypass with cardioplegic arrest (with or without deep hypothermic circulatory arrest)
• Diagnosis with cyanosis at baseline (pre-operative PaO2 of less than 50mmHG) due to:
• Complete admixture lesion (example: hypoplastic left heart syndrome, total anomalous pulmonary venous return, truncus arteriosus, pulmonary atresia with VSD)
• Transposition physiology (example: D-Transposition of the great arteries or Double outlet right ventricle with subpulmonary VSD)
• Right-to-left shunt (example: Tetralogy of Fallot, double outlet right ventricle with subaortic VSD and pulmonary stenosis)

You may not qualify if:

• Corrected gestation at time of surgery less than 37 weeks
• Prior cardiac arrest
• Current or prior history of extracorporeal membrane oxygenation (ECMO) support
• Current or prior history of needing renal replacement therapy with dialysis
• Prior cardiac surgery requiring cardiopulmonary bypass
• Diagnosis of Ebstein's Anomaly
• Known genetic syndrome other than Trisomy 21 or DiGeorge Syndrome

Sponsors & Collaborators

• University of Michigan: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Hypoplastic Left Heart Syndrome; Scimitar Syndrome; Truncus Arteriosus, Persistent; Pulmonary Atresia With Ventricular Septal Defect; Transposition of Great Vessels; Double Outlet Right Ventricle; Tetralogy of Fallot; Pulmonary Valve Stenosis

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Respiratory System Abnormalities; Vascular Malformations; Vascular Diseases; Aortopulmonary Septal Defect; Heart Septal Defects; Heart Septal Defects, Ventricular; Heart Valve Diseases; Ventricular Outflow Obstruction

Results Point of Contact

• Title: Dr. Nathaniel Sznycer-Taub
• Organization: The University of Michigan Health System

nsznycer@umich.edu

734-936-8993

Study Officials

• Nathaniel Sznycer-Taub, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: June 30, 2020
• Study Start: January 18, 2021
• Primary Completion: April 20, 2023
• Study Completion: April 20, 2023
• Last Updated: June 18, 2024
• Results First Posted: June 18, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)