Hypoplastic Left Heart SyndromeT-NOXNCT04452188
Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period
A study of Hypoplastic Left Heart Syndrome and Total Anomalous Pulmonary Venous Return, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 29 days
- Conditions the study is for
- Hypoplastic Left Heart Syndrome, Total Anomalous Pulmonary Venous Return, Truncus Arteriosus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2021to 20 Apr 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 29 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period (T-NOX)
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.
Read more
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
- Being tested
- Normoxia (with controlled re-oxygenation), Standard of care ventilation
- Keywords
- Open heart surgery
- Medical subject headings
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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:
- Single ventricle patients (PaO2:35-45 and oxygen saturation 75%-85%)
- Two ventricle patients (PaO2: 60-100 and oxygen saturation >92%)
Standard of care ventilationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Other: Standard of care ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 30 days after surgery
Post-operative Length of Stay
Calculated as number of days in the hospital after surgery.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2020
- Study start18 Jan 2021
- Primary completion20 Apr 2023
- Study completion20 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypoplastic Left Heart SyndromeStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Nathaniel Sznycer-Taub, University of Michigan
- Investigators
- Nathaniel Sznycer-Taub, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04452188
- Sponsor's protocol ID
- HUM00175086
- Other IDs
- 5UL1TR002240-05
- Acronym
- T-NOX
- Status last verified
- May 2024
- First submitted
- 22 Jun 2020
- Last updated
- 18 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period (T-NOX)
- ClinicalTrials.gov ID
- NCT04452188
- Acronym / sponsor ID
- T-NOX / HUM00175086
- 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
- Keywords
- Open heart surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)
- Study start
- 18 Jan 2021 (actual)
- Primary completion
- 20 Apr 2023 (actual)
- Study completion
- 20 Apr 2023 (actual)
- First posted
- 30 Jun 2020 (actual)
- Results
- Posted 18 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normoxia | Experimental | Other: 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 | Active comparator | Other: Standard of care ventilationFrequent 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 |
Who may qualify
- Ages
- Up to 29 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Normoxia (with controlled re-oxygenation)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%) | Other | Normoxia |
| Standard of care ventilationAs 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. | Other | Standard of care |
Primary outcome
Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS)
Time frame: 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.
Rate of Observed Adverse Events Between the Two Groups
Time frame: 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.
Post-operative Length of Stay
Time frame: 30 days after surgery
Calculated as number of days in the hospital after surgery.
Days Alive and Out of the Intensive Care Unit (ICU) at 30 Days After Surgery
Time frame: 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.
Composite Outcome of Major Adverse Events
Time frame: 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.
Global Rank Score
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nathaniel Sznycer-Taub, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Hypoplastic Left Heart Syndrome and Total Anomalous Pulmonary Venous Return, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Systemic Oxidative Stress Based on Thiobarbituric Acid Reactive Substances (TBARS) (time frame: Up to 24 hours following surgery). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2024.