ChildrenPhase 3NCT02481791
Study to Evaluate the Optimal Dose of Remifentanil During MRI of the Heart Under General Anaesthesia
A Phase 3 study testing Remifentanil and/or propofol and propofol in people with Children and Heart Diseases, run by Alder Hey Children's NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
What is the optimal maintenance dose of remifentanil to ensure apnoea, during breath hold episodes in children having cardiac MR imaging with general anaesthesia? Read more about this study
- Who is it for?
- Ages 1 year to 7 years
- Conditions the study is for
- Children, Heart Diseases, Anaesthesia
- What is being tested?
- Remifentanil and/or propofol and propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jul 2015to 31 Dec 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 year to 7 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children of one year (of age) or older and younger than 7 years of age.
- Scheduled for cardiac MR imaging under general anaesthesia at Alder Hey Children's Hospital.
- Parental Consent
Who cannot join
- Hypersensitivity to any study drug
- Known abnormal response to opiate analgesics or co-morbidity associated with abnormal central control of breathing
- Families unable to understand or complete consent
- Any other contraindication to proposed anaesthetic technique: at the discretion of the responsible anaesthetist.
- Documented significant renal or hepatic dysfunction
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Alder Hey Children's Hospital
Liverpool, Merseyside, L12 2AP
Phillip Arnold, 0151 228 4811, Philip.Arnold@alderhey.nhs.uk
Syed Sanaulla, 0151 228 4811, Sanaulla.Syed@alderhey.nhs.uk
About this study
Official title: Study to Evaluate the Optimal Dose of Remifentanil Required to Ensure Apnoea During Magnetic Resonance Imaging of the Heart Under General Anaesthesia
What is the optimal maintenance dose of remifentanil to ensure apnoea, during breath hold episodes in children having cardiac MR imaging with general anaesthesia?
Read the detailed description
The management of congenital heart disease depends upon accurate imaging of the heart to define anatomical abnormalities. The use of magnetic resonance imaging has grown in response to this need. Young children, however, are unable to cooperate sufficiently to allow the scan to occur; this necessitates the use of general anaesthesia.
The optimal anaesthetic management of children in this situation is complex. Imaging of an acceptable quality depends on a low (normal) heart rate which is relatively constant during the scan and frequent breath holds to avoid respiratory artefacts. Children undergoing such scans commonly have significant cardiac and non-cardiac disease. A technique, currently used at Alder Hey Hospital, is to use intravenous agents to provide anaesthesia: commonly a mixture of the intravenous anaesthetic propofol and the potent opiate remifentanil. The patient's own ventilation is suppressed by the use of remifentanil which also reduces heart rate and heart rate variability. Controlled ventilation is provided via a ventilator and endotracheal tube. Adequate doses of remifentanil are required to ensure suppression of the patient's ventilation whilst excess doses are avoided to reduce the risk of adverse effects (primarily arterial hypotension) and ensure rapid recovery.
Remifentanil dose has been studied during surgery(3-6), however this is a unique indication and optimal dosage has not been formally studied. In particular the absence of any stimulation from surgery is likely to mean that substantially lower doses of remifentanil will be required.
- Conditions
- Children, Heart Diseases, Anaesthesia, Magnetic Resonance Imaging
- Being tested
- Remifentanil and/or propofol, propofol
- Medical subject headings
- Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remifentanil and/or propofolDrug
Induction Phase: A dose of remifentanil 1mcg/kg by slow bolus, will be given to facilitate endotracheal intubation. Further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given to ensure an anaesthetised patient.
Remifentanil and/or propofolDrug
Settling Period: An infusion of the test dose of remifentanil will be commenced from an infusion prepared prior to the patient being anaesthetised. 1mg of Remifentanil (one vial) will be diluted to a volume of 50mls in normal saline 0.9% in a 50ml syringe. Maintenance dose of propofol 130 mcg/Kg/min for the first 5 minutes reduced to 100 mcg/kg/min thereafter. 40mls of propofol 1% (10mg/ml) will be drawn undiluted into a 50ml syringe. During the settling period further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given.
propofolDrug
Equilibrium Period: During this period propofol will be infused at a constant rate of 100mcg/kg/min
| Study group | Role | What they receive |
|---|---|---|
| Remifentanil | Experimental | Induction Phase: A dose of remifentanil 1mcg/kg by slow bolus, will be given to facilitate endotracheal intubation. Further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given to ensure an anaesthetised patient.
Settling Period: An infusion of the test dose of remifentanil will be commenced from an infusion prepared prior to the patient being anaesthetised. 1mg of Remifentanil (one vial) will be diluted to a volume of 50mls in normal saline 0.9% in a 50ml syringe. Maintenance dose of propofol 130 mcg/Kg/min for the first 5 minutes reduced to 100 mcg/kg/min thereafter. 40mls of propofol 1% (10mg/ml) will be drawn undiluted into a 50ml syringe. During the settling period further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given.
Equilibrium Period: During this period propofol will be infused at a constant rate of 100mcg/kg/min. Receives: Drug: Remifentanil and/or propofol; Drug: propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diaphragm movement
The primary outcome will be movement of the diaphragm during the single test apnoea. The dose of remifentanil will be judged:
- A success. If no movement of the diaphragm is detected by MRI imaging during a 30 second test apnoea.
- A failure. If movement of the diaphragm is detected during the test apnoea.
Measured: 30 seconds
Secondary outcomes (4)
Scan Quality
- quality of the scan from the respiratory gated sequence (graded by the radiologist who will be blinded to the dose)
Measured: 1 hour
Heart Rate
- highest and lowest heart rate (during equilibrium and study period)
Measured: 1 hour
Blood pressure
- lowest blood pressure (during equilibrium and study period)
Measured: 1 hour
Emergence time
- time to emergence (waking up) at end of scan
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2015 (estimated)
- Study startJul 2015
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for ChildrenStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alder Hey Children's NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02481791
- Sponsor's protocol ID
- 146613
- Status last verified
- Jan 2019
- First submitted
- 19 Jun 2015
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Syed SK, Corry P. Cardiac Imaging under general anaesthesia for children with congenital heart disease. Our experience. Abstract presentation, APAGBI scientific meeting. 2012.
Chanavaz C, Tirel O, Wodey E, Bansard JY, Senhadji L, Robert JC, Ecoffey C. Haemodynamic effects of remifentanil in children with and without intravenous atropine. An echocardiographic study. Br J Anaesth. 2005 Jan;94(1):74-9. doi: 10.1093/bja/aeh293. Epub 2004 Oct 14.
PubMed 15486003Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg. 2005 Jun;100(6):1599-1604. doi: 10.1213/01.ANE.0000150940.57369.B5.
PubMed 15920180Hume-Smith H, McCormack J, Montgomery C, Brant R, Malherbe S, Mehta D, Ansermino JM. The effect of age on the dose of remifentanil for tracheal intubation in infants and children. Paediatr Anaesth. 2010 Jan;20(1):19-27. doi: 10.1111/j.1460-9592.2009.03190.x. Epub 2009 Nov 23.
PubMed 19968808Min SK, Kwak YL, Park SY, Kim JS, Kim JY. The optimal dose of remifentanil for intubation during sevoflurane induction without neuromuscular blockade in children. Anaesthesia. 2007 May;62(5):446-50. doi: 10.1111/j.1365-2044.2007.05037.x.
PubMed 17448054Ross AK, Davis PJ, Dear Gd GL, Ginsberg B, McGowan FX, Stiller RD, Henson LG, Huffman C, Muir KT. Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures. Anesth Analg. 2001 Dec;93(6):1393-401, table of contents. doi: 10.1097/00000539-200112000-00008.
PubMed 11726413Whitehead J, Brunier H. Bayesian decision procedures for dose determining experiments. Stat Med. 1995 May 15-30;14(9-10):885-93; discussion 895-9. doi: 10.1002/sim.4780140904.
PubMed 7569508Whitehead J, Williamson D. Bayesian decision procedures based on logistic regression models for dose-finding studies. J Biopharm Stat. 1998 Jul;8(3):445-67. doi: 10.1080/10543409808835252.
PubMed 9741859Zhou Y, Whitehead J. Practical Implementation of Bayesian Dose-Escalation Procedures. Drug Information Journal. 2003;37(1):45-59.
R Core Team R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2013.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate the Optimal Dose of Remifentanil Required to Ensure Apnoea During Magnetic Resonance Imaging of the Heart Under General Anaesthesia
- ClinicalTrials.gov ID
- NCT02481791
- Acronym / sponsor ID
- 146613
- Conditions
- Children, Heart Diseases, Anaesthesia, Magnetic Resonance Imaging
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Alder Hey Children's NHS Foundation TrustUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 25 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
What is the optimal maintenance dose of remifentanil to ensure apnoea, during breath hold episodes in children having cardiac MR imaging with general anaesthesia?
Detailed description
The management of congenital heart disease depends upon accurate imaging of the heart to define anatomical abnormalities. The use of magnetic resonance imaging has grown in response to this need. Young children, however, are unable to cooperate sufficiently to allow the scan to occur; this necessitates the use of general anaesthesia.
The optimal anaesthetic management of children in this situation is complex. Imaging of an acceptable quality depends on a low (normal) heart rate which is relatively constant during the scan and frequent breath holds to avoid respiratory artefacts. Children undergoing such scans commonly have significant cardiac and non-cardiac disease. A technique, currently used at Alder Hey Hospital, is to use intravenous agents to provide anaesthesia: commonly a mixture of the intravenous anaesthetic propofol and the potent opiate remifentanil. The patient's own ventilation is suppressed by the use of remifentanil which also reduces heart rate and heart rate variability. Controlled ventilation is provided via a ventilator and endotracheal tube. Adequate doses of remifentanil are required to ensure suppression of the patient's ventilation whilst excess doses are avoided to reduce the risk of adverse effects (primarily arterial hypotension) and ensure rapid recovery.
Remifentanil dose has been studied during surgery(3-6), however this is a unique indication and optimal dosage has not been formally studied. In particular the absence of any stimulation from surgery is likely to mean that substantially lower doses of remifentanil will be required.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Remifentanil | Experimental | Drug: Remifentanil and/or propofol, Drug: propofolInduction Phase: A dose of remifentanil 1mcg/kg by slow bolus, will be given to facilitate endotracheal intubation. Further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given to ensure an anaesthetised patient. Settling Period: An infusion of the test dose of remifentanil will be commenced from an infusion prepared prior to the patient being anaesthetised. 1mg of Remifentanil (one vial) will be diluted to a volume of 50mls in normal saline 0.9% in a 50ml syringe. Maintenance dose of propofol 130 mcg/Kg/min for the first 5 minutes reduced to 100 mcg/kg/min thereafter. 40mls of propofol 1% (10mg/ml) will be drawn undiluted into a 50ml syringe. During the settling period further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given. Equilibrium Period: During this period propofol will be infused at a constant rate of 100mcg/kg/min. |
Who may qualify
- Ages
- 1 year to 7 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Children of one year (of age) or older and younger than 7 years of age.
- Scheduled for cardiac MR imaging under general anaesthesia at Alder Hey Children's Hospital.
- Parental Consent
Key exclusion criteria (5 listed)
- Hypersensitivity to any study drug
- Known abnormal response to opiate analgesics or co-morbidity associated with abnormal central control of breathing
- Families unable to understand or complete consent
- Any other contraindication to proposed anaesthetic technique: at the discretion of the responsible anaesthetist.
- Documented significant renal or hepatic dysfunction
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 |
|---|---|---|
| Remifentanil and/or propofolInduction Phase: A dose of remifentanil 1mcg/kg by slow bolus, will be given to facilitate endotracheal intubation. Further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given to ensure an anaesthetised patient. | Drug | Remifentanil |
| Remifentanil and/or propofolSettling Period: An infusion of the test dose of remifentanil will be commenced from an infusion prepared prior to the patient being anaesthetised. 1mg of Remifentanil (one vial) will be diluted to a volume of 50mls in normal saline 0.9% in a 50ml syringe. Maintenance dose of propofol 130 mcg/Kg/min for the first 5 minutes reduced to 100 mcg/kg/min thereafter. 40mls of propofol 1% (10mg/ml) will be drawn undiluted into a 50ml syringe. During the settling period further doses of either remifentanil (0.5 mcg/kg) or propofol (1-2mg/kg) may be given. | Drug | Remifentanil |
| propofolEquilibrium Period: During this period propofol will be infused at a constant rate of 100mcg/kg/min | Drug | Remifentanil |
Primary outcome
Diaphragm movement
Time frame: 30 seconds
The primary outcome will be movement of the diaphragm during the single test apnoea. The dose of remifentanil will be judged: * A success. If no movement of the diaphragm is detected by MRI imaging during a 30 second test apnoea. * A failure. If movement of the diaphragm is detected during the test apnoea.
4 secondary outcomes
Scan Quality
Time frame: 1 hour
Heart Rate
Time frame: 1 hour
Blood pressure
Time frame: 1 hour
Emergence time
Time frame: 1 hour
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- BackgroundSyed SK, Corry P. Cardiac Imaging under general anaesthesia for children with congenital heart disease. Our experience. Abstract presentation, APAGBI scientific meeting. 2012.
- Background: PubMed 15486003Chanavaz C, Tirel O, Wodey E, Bansard JY, Senhadji L, Robert JC, Ecoffey C. Haemodynamic effects of remifentanil in children with and without intravenous atropine. An echocardiographic study. Br J Anaesth. 2005 Jan;94(1):74-9. doi: 10.1093/bja/aeh293. Epub 2004 Oct 14.
- Background: PubMed 15920180Crawford MW, Hayes J, Tan JM. Dose-response of remifentanil for tracheal intubation in infants. Anesth Analg. 2005 Jun;100(6):1599-1604. doi: 10.1213/01.ANE.0000150940.57369.B5.
- Background: PubMed 19968808Hume-Smith H, McCormack J, Montgomery C, Brant R, Malherbe S, Mehta D, Ansermino JM. The effect of age on the dose of remifentanil for tracheal intubation in infants and children. Paediatr Anaesth. 2010 Jan;20(1):19-27. doi: 10.1111/j.1460-9592.2009.03190.x. Epub 2009 Nov 23.
- Background: PubMed 17448054Min SK, Kwak YL, Park SY, Kim JS, Kim JY. The optimal dose of remifentanil for intubation during sevoflurane induction without neuromuscular blockade in children. Anaesthesia. 2007 May;62(5):446-50. doi: 10.1111/j.1365-2044.2007.05037.x.
- Background: PubMed 11726413Ross AK, Davis PJ, Dear Gd GL, Ginsberg B, McGowan FX, Stiller RD, Henson LG, Huffman C, Muir KT. Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures. Anesth Analg. 2001 Dec;93(6):1393-401, table of contents. doi: 10.1097/00000539-200112000-00008.
- Background: PubMed 7569508Whitehead J, Brunier H. Bayesian decision procedures for dose determining experiments. Stat Med. 1995 May 15-30;14(9-10):885-93; discussion 895-9. doi: 10.1002/sim.4780140904.
- Background: PubMed 9741859Whitehead J, Williamson D. Bayesian decision procedures based on logistic regression models for dose-finding studies. J Biopharm Stat. 1998 Jul;8(3):445-67. doi: 10.1080/10543409808835252.
- BackgroundZhou Y, Whitehead J. Practical Implementation of Bayesian Dose-Escalation Procedures. Drug Information Journal. 2003;37(1):45-59.
- BackgroundR Core Team R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2013.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Remifentanil and/or propofol and propofol in people with Children and Heart Diseases, run by Alder Hey Children's NHS Foundation Trust at 1 site in United Kingdom.
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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 10 Jan 2019. 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 Kingdom. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diaphragm movement (time frame: 30 seconds). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02481791, which also lists 10 linked publications.
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 10 Jan 2019.