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

Not Applicable

Completed

• Conditions: Tetralogy of Fallot; Cardiopulmonary Bypass; Total Anomalous Pulmonary Venous Return; Pulmonary Atresia With Ventricular Septal Defect; Double Outlet Right Ventricle With Subaortic Ventricular Septal Defect and Pulmonary Stenosis; Truncus Arteriosus; Transposition of the Great Arteries; Hypoplastic Left Heart Syndrome; Double Outlet Right Ventricle, Subpulmonary VSD
• Interventions: Other: Normoxia (with controlled re-oxygenation); Other: Standard of care ventilation

• Registration Number: NCT04452188
• Lead Sponsor: University of Michigan

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

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-06-22
• Study First Submitted QC: 2020-06-27
• Study First Posted: 2020-06-30
• Study Start: 2021-01-18
• Primary Completion: 2023-04-20
• Study Completion: 2023-04-20
• Results First Submitted: 2024-04-23
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-22
• Last Update Submitted: 2024-05-22
• Results First Posted: 2024-06-18
• Last Update Posted: 2024-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• 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)

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Exclusion Criteria

• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normoxia	Normoxia (with controlled re-oxygenation)	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.
Standard of care	Standard of care ventilation	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

Primary Outcome Measures

Name	Time	Method
Rate of Observed Adverse Events Between the Two Groups	30 days after surgery	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.
Global Rank Score	30 days after surgery	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.
Days Alive and Out of the Intensive Care Unit (ICU) at 30 Days After Surgery	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.
Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS)	Up to 24 hours following surgery	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.
Post-operative Length of Stay	30 days after surgery	Calculated as number of days in the hospital after surgery.
Composite Outcome of Major Adverse Events	30 days after surgery	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.

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States