Anesthesia; Adverse EffectNDONCT03882788
The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
A study testing Isoflurane, Fentanyl (high dose) and Fentanyl (low dose) in people with Anesthesia; Adverse Effect and Congenital Heart Disease, run by Stanford University at 1 site in United States.
Trial summary
The purpose of this study is to assess whether the type of anesthesia, narcotic-based versus inhalational anesthesia administered during cardiopulmonary bypass (CPB) surgery contributes to the wide variation in neurologic recovery and developmental outcome after surgery in infants with congenital heart disease. Read more about this study
- Who is it for?
- Ages 1 day to 36 months
- Conditions the study is for
- Anesthesia; Adverse Effect, Congenital Heart Disease, Neurodevelopmental Disorders
- What is being tested?
- Isoflurane, Fentanyl (high dose) and Fentanyl (low dose)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Apr 2013to 19 Nov 2020
- 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 1 day to 36 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Neonates of at least 32 weeks of gestation, infants and children up to 2 years of age admitted to The Children's Hospital for treatment of cyanotic or non-cyanotic heart disease requiring surgical intervention.
- Admitting diagnosis of cyanotic or non-cyanotic heart disease
Who cannot join
- Neonates less than 32 weeks of gestational age, and children more than 2 years of age.
- Any documented central nervous system malformations.
- Any potential subject requiring unexpected postoperative Extracorporeal membrane oxygenation (ECMO) support
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford Childrens hospital
Palo Alto, California, 94305
About this study
Official title: Anesthesia and the Developing Brain: a Comparison of Two Anesthetic Techniques
The purpose of this study is to assess whether the type of anesthesia, narcotic-based versus inhalational anesthesia administered during cardiopulmonary bypass (CPB) surgery contributes to the wide variation in neurologic recovery and developmental outcome after surgery in infants with congenital heart disease.
Read the detailed description
All subjects will be consented prior to participation in this study and prior to randomization.
All the subjects enrolled in the study will receive a preoperative assessment by one of the cardiac anesthesiologists and receive standardized induction with sevoflurane up to 2%, 2 mcg/kg of fentanyl and 1 mg/kg of rocuronium. The anesthetic maintenance will be determined using a computer- generated randomization table and assigning each patient to one of the two anesthetic regimens. Both of these anesthetic techniques are standard of care and are commonly used for these procedures.
Anesthetic Technique:
Volatile anesthetic:
In volatile anesthetic technique, maintenance of anesthesia will be standardized to the volatile anesthetic isoflurane. Isoflurane will be used for the study since this is what is presently available on the CPB machines. Anesthesia at 1.0 minimum anesthetic concentration (MAC) indicates that at this concentration 50% of the patients will not move when surgically stimulated. Anesthesiologists commonly use about 1.2-1.4 MAC in neonates, since the MAC value in infants is higher than that of children and adults. Isoflurane will be delivered at 1.5-2.0%% as required for anesthetic management.
Rocuronium or pancuronium will be used for muscle relaxation. Narcotic, fentanyl will be administered at no greater than 2 mcg/kg/hr.
Narcotic-based anesthetic:
In narcotic based anesthetic technique, no volatile anesthetics will be used except during induction.
Maintenance of anesthesia will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr.
The anesthetic may be supplemented with dexmedetomidine 0.05 mcg/kg/hr but not to exceed 1.0 mcg/kg/hr. Narcotic-based anesthetic will be used by the cardiac anesthesia team and the CPB technician throughout the operative case. 5 mcg/kg/hr of fentanyl is felt to represent 0.6 MAC of anesthesia.
Postoperative Sedative and Analgesic Care:
As per institutional standard of care, postoperative sedation will consist of fentanyl infusions of 2-4 mcg/kg/hr for the first 48 hours postoperatively.
A total of 9 Blood samples will be collected at different time points throughout the entire study for metabolomics determination (NAA/Cr and Chol/Cr)
EEG monitoring will be done for baseline in the pre-operative period for 15-20 minutes, during surgery and post-operatively up to 48 hours and prior to discharge for 15-20 minutes. Neurological and behavioral testing including Bayley Exam III will be done at 18-48 months.
- Being tested
- Isoflurane, Fentanyl (high dose), Fentanyl (low dose)
- Medical subject headings
- Heart Defects, Congenital, Neurodevelopmental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsofluraneDrug
Isoflurane (volatile anesthesia) will be delivered at 1.5-2.0%% as required for anesthetic management.
Fentanyl (high dose)Drug
Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr.
Fentanyl (low dose)Drug
Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 2 mcg/kg/hr.
| Study group | Role | What they receive |
|---|---|---|
| Volatile Anesthesia | Active comparator | In volatile anesthetic technique, maintenance of anesthesia will be standardized to the anesthesia will be standardized to the volatile anesthetic isoflurane.
Rocuronium or pancuronium will be used for muscle relaxation. Additionally, narcotic fentanyl will be administered at no greater than 2 mcg/kg/hr (low dose). However, the primary anesthetic during CPB will be isoflurane with no narcotic administered during CPB. Receives: Drug: Isoflurane; Drug: Fentanyl (low dose) |
| Narcotic based anesthesia | Active comparator | In narcotic based anesthetic technique, no volatile anesthetics will be used past induction.
Maintenance of anesthesia will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr (high dose). Receives: Drug: Fentanyl (high dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bayley III
Neurodevelopmental assessment scores are age dependent and based motor and behavioral abilities, often reported for normal or abnormal for age. Bayley Scales of Infant and Toddler Development, third edition, (Bayley III) is an instrument designed to measure the developmental functioning of infants and toddlers between the ages of 1 month and 42 months (age adjustments for prematurity are accommodated with the tool). It provides age specific composite scores for cognitive (91 items, score min 55 max 145), language (98 items, score min 47 max 153), and motor (138 items, score min 46 max 154) skills. For all scales, higher scores are better and lower scores indicate possible delay/deficit.
Measured: Assessed once between age 18 to 48 months (approximately 2 hours to assess), up to 48 months from study start
Electroencephalogram
Brain electrical activity: observation is for brain region specific abnormal or seizure activity. Number of participants with abnormal EEG are reported.
Measured: EEG taken immediately prior to surgery, during surgery, during cardiovascular intensive care unit (CVICU) stay (up to 48 hours after surgery), and immediately prior to discharge (between 5 to 20 minutes to assess EEG at each time point)
Secondary outcomes (4)
Choline
blood levels: time and patient dependent variation, observed patient related trends over time
Measured: 0-72 hours
Glutamate
blood levels:time and patient dependent variation, observed patient related trends over time
Measured: 0-72 hours
N-acetylaspartate (Naa)
blood levels:time and patient dependent variation, observed patient related trends over time
Measured: 0-72 hours
Lactate
blood levels:time and patient dependent variation, observed patient related trends over time
Measured: 0-72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2019
- Study start22 Apr 2013
- Primary completion19 Nov 2020
- Study completion19 Nov 2020
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 Anesthesia; Adverse EffectStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- The Gerber Foundation
- Responsible party
- Sponsor
- Investigators
- Lisa W Faberowski, MD, MSc, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03882788
- Sponsor's protocol ID
- NDO
- Acronym
- NDO
- Status last verified
- May 2022
- First submitted
- 5 May 2016
- Last updated
- 9 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: No IPD will be shared with other researchers
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anesthesia and the Developing Brain: a Comparison of Two Anesthetic Techniques
- ClinicalTrials.gov ID
- NCT03882788
- Acronym / sponsor ID
- NDO / NDO
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- The Gerber Foundation
- Study start
- 22 Apr 2013 (actual)
- Primary completion
- 19 Nov 2020 (actual)
- Study completion
- 19 Nov 2020 (actual)
- First posted
- 20 Mar 2019 (actual)
- Results
- Posted 9 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess whether the type of anesthesia, narcotic-based versus inhalational anesthesia administered during cardiopulmonary bypass (CPB) surgery contributes to the wide variation in neurologic recovery and developmental outcome after surgery in infants with congenital heart disease.
Detailed description
All subjects will be consented prior to participation in this study and prior to randomization.
All the subjects enrolled in the study will receive a preoperative assessment by one of the cardiac anesthesiologists and receive standardized induction with sevoflurane up to 2%, 2 mcg/kg of fentanyl and 1 mg/kg of rocuronium. The anesthetic maintenance will be determined using a computer- generated randomization table and assigning each patient to one of the two anesthetic regimens. Both of these anesthetic techniques are standard of care and are commonly used for these procedures.
Anesthetic Technique:
Volatile anesthetic:
In volatile anesthetic technique, maintenance of anesthesia will be standardized to the volatile anesthetic isoflurane. Isoflurane will be used for the study since this is what is presently available on the CPB machines. Anesthesia at 1.0 minimum anesthetic concentration (MAC) indicates that at this concentration 50% of the patients will not move when surgically stimulated. Anesthesiologists commonly use about 1.2-1.4 MAC in neonates, since the MAC value in infants is higher than that of children and adults. Isoflurane will be delivered at 1.5-2.0%% as required for anesthetic management.
Rocuronium or pancuronium will be used for muscle relaxation. Narcotic, fentanyl will be administered at no greater than 2 mcg/kg/hr.
Narcotic-based anesthetic:
In narcotic based anesthetic technique, no volatile anesthetics will be used except during induction.
Maintenance of anesthesia will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr.
The anesthetic may be supplemented with dexmedetomidine 0.05 mcg/kg/hr but not to exceed 1.0 mcg/kg/hr. Narcotic-based anesthetic will be used by the cardiac anesthesia team and the CPB technician throughout the operative case. 5 mcg/kg/hr of fentanyl is felt to represent 0.6 MAC of anesthesia.
Postoperative Sedative and Analgesic Care:
As per institutional standard of care, postoperative sedation will consist of fentanyl infusions of 2-4 mcg/kg/hr for the first 48 hours postoperatively.
A total of 9 Blood samples will be collected at different time points throughout the entire study for metabolomics determination (NAA/Cr and Chol/Cr)
EEG monitoring will be done for baseline in the pre-operative period for 15-20 minutes, during surgery and post-operatively up to 48 hours and prior to discharge for 15-20 minutes. Neurological and behavioral testing including Bayley Exam III will be done at 18-48 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Volatile Anesthesia | Active comparator | Drug: Isoflurane, Drug: Fentanyl (low dose)In volatile anesthetic technique, maintenance of anesthesia will be standardized to the anesthesia will be standardized to the volatile anesthetic isoflurane. Rocuronium or pancuronium will be used for muscle relaxation. Additionally, narcotic fentanyl will be administered at no greater than 2 mcg/kg/hr (low dose). However, the primary anesthetic during CPB will be isoflurane with no narcotic administered during CPB. |
| Narcotic based anesthesia | Active comparator | Drug: Fentanyl (high dose)In narcotic based anesthetic technique, no volatile anesthetics will be used past induction. Maintenance of anesthesia will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr (high dose). |
Who may qualify
- Ages
- 1 day to 36 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Neonates of at least 32 weeks of gestation, infants and children up to 2 years of age admitted to The Children's Hospital for treatment of cyanotic or non-cyanotic heart disease requiring surgical intervention.
- Admitting diagnosis of cyanotic or non-cyanotic heart disease
Key exclusion criteria (3 listed)
- Neonates less than 32 weeks of gestational age, and children more than 2 years of age.
- Any documented central nervous system malformations.
- Any potential subject requiring unexpected postoperative Extracorporeal membrane oxygenation (ECMO) support
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 |
|---|---|---|
| IsofluraneIsoflurane (volatile anesthesia) will be delivered at 1.5-2.0%% as required for anesthetic management. | Drug | Volatile Anesthesia |
| Fentanyl (high dose)Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 5 mcg/kg/hr not to exceed 10 mcg/kg/hr. | Drug | Narcotic based anesthesia |
| Fentanyl (low dose)Fentanyl (narcotic anesthesia) maintenance will be with fentanyl 2 mcg/kg/hr. | Drug | Volatile Anesthesia |
Primary outcome
Bayley III
Time frame: Assessed once between age 18 to 48 months (approximately 2 hours to assess), up to 48 months from study start
Neurodevelopmental assessment scores are age dependent and based motor and behavioral abilities, often reported for normal or abnormal for age. Bayley Scales of Infant and Toddler Development, third edition, (Bayley III) is an instrument designed to measure the developmental functioning of infants and toddlers between the ages of 1 month and 42 months (age adjustments for prematurity are accommodated with the tool). It provides age specific composite scores for cognitive (91 items, score min 55 max 145), language (98 items, score min 47 max 153), and motor (138 items, score min 46 max 154) skills. For all scales, higher scores are better and lower scores indicate possible delay/deficit.
Electroencephalogram
Time frame: EEG taken immediately prior to surgery, during surgery, during cardiovascular intensive care unit (CVICU) stay (up to 48 hours after surgery), and immediately prior to discharge (between 5 to 20 minutes to assess EEG at each time point)
Brain electrical activity: observation is for brain region specific abnormal or seizure activity. Number of participants with abnormal EEG are reported.
4 secondary outcomes
Choline
Time frame: 0-72 hours
Glutamate
Time frame: 0-72 hours
N-acetylaspartate (Naa)
Time frame: 0-72 hours
Lactate
Time frame: 0-72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No IPD will be shared with other researchers
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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.
Lisa W Faberowski, MD, MSc principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Isoflurane, Fentanyl (high dose) and Fentanyl (low dose) in people with Anesthesia; Adverse Effect and Congenital Heart Disease, run by Stanford University 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 2 inclusion and 3 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 9 May 2022. 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 9 May 2022). 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?
Bayley III (time frame: Assessed once between age 18 to 48 months (approximately 2 hours to assess), up to 48 months from study start). The study lists 2 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 9 May 2022.