Myocardial RepolarizationPhase 4DexmedQTNCT02353169
The Effects of Dexmedetomidine on the Heart Beat During Elective Surgery in Children
A Phase 4 study testing Dexmedetomidine and Saline in people with Myocardial Repolarization and Healthy, run by University of British Columbia at 1 site in Canada.
Trial summary
Dexmedetomidine is a sedative drug that is commonly used to improve calmness and reduce pain in children waking up after surgery. Some of the side effects of dexmedetomidine, such as a potential change in how the heart muscles contract and changes in blood sugar and potassium levels, are poorly understood. Read more about this study
- Who is it for?
- Ages 3 to 10 years
- Conditions the study is for
- Myocardial Repolarization, Healthy
- What is being tested?
- Dexmedetomidine and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2015to Dec 2017
- Phase
- Phase 4
- 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 3 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ASA Physical Status I-II
- Age 3 to 10yrs
- Elective surgical procedure requiring general anesthesia
- Use of dexmedetomidine acceptable to the staff anesthesiologist
- Un-premedicated
- Ability to read and understand English (parent/legal guardian(s) and child)
Who cannot join
- Long QT syndrome (LQTS)
- Cardiac disease or rhythm abnormalities
- Family history of LQTS or abnormal cardiac conduction
- Currently taking medications known to prolong QT
- Currently taking medications known to predispose to hypokalemia
- Known hypersensitivity to dexmedetomidine or other study medication
Show all 11Show fewer
- Weight < 5th centile or > 95th centile for age
- Previously diagnosed hypokalemia
- Impaired renal or liver function
- Pre-operative anxiety requiring sedatives or opioids
- Refusal to participate
Trial locations and contacts
1 site in 1 country.
Canada1 site
BC Children's Hospital - Department of Anesthesia
Vancouver, British Columbia, V6H 3V4
About this study
Official title: The Effects of Dexmedetomidine on Myocardial Repolarization in Children
Dexmedetomidine is a sedative drug that is commonly used to improve calmness and reduce pain in children waking up after surgery. Some of the side effects of dexmedetomidine, such as a potential change in how the heart muscles contract and changes in blood sugar and potassium levels, are poorly understood. The current study aims to examine these changes directly in healthy children undergoing elective surgery by measuring the heart beats (with an electrocardiogram) and blood sugar and potassium at specific times before and after dexmedetomidine is given. The investigators aim to establish a better understanding of this drug's safety profile.
Read the detailed description
Purpose:
This study is being conducted to evaluate the effect of three different doses of dexmedetomidine (Precedex® , Hospira Healthcare) on myocardial repolarization, and blood glucose and potassium levels in children undergoing elective surgery.
Hypotheses:
The investigators hypothesize that administering a dexmedetomidine bolus will have some effect on myocardial repolarization, blood glucose, and potassium concentrations in a dose-dependent manner, whereas a saline bolus will not.
Justification:
Dexmedetomidine is a potent, centrally acting α-2 adrenoreceptor agonist with sympatholytic, sedative, amnestic, anxiolytic and analgesic effects, which properties make it popular for use in both pediatric anesthesia and intensive care. In 2013, dexmedetomidine was added to the "possible risk factor for torsades de pointes (TdP)" drug list on crediblemeds.org. Clinicians are currently advised to be vigilant about potential QT prolongation with dexmedetomidine, especially in patients with congenital long QT syndrome (LQTS). However, current evidence for dexmedetomidine-induced prolonged QT is sparse and somewhat contradictory, and the effect of dexmedetomidine on the Tp-e interval has yet to be reported in detail in adults or children. Another poorly defined pharmacodynamic effect of dexmedetomidine is its effect on blood glucose concentration. Theoretically, dexmedetomidine would be expected to cause hypoinsulinaemia and a resultant increase in blood glucose levels (hyperglycemia). Previous studies are in contrast to this however; with reports of hypoglycemia after large doses of the drug. Considering the use of dexmedetomidine in pediatric anesthesia, pediatric intensive care and its increasing use in the neonatal population, increased knowledge of the effect of dexmedetomidine on blood glucose would be valuable.
Finally, hypokalemia is listed as a treatment-emergent adverse event occurring in >2% of adult patients receiving dexmedetomidine in long-term intensive care unit sedation studies. The effect of dexmedetomidine on serum potassium levels in healthy children has yet to be elucidated. Given that hypokalemia increases the risk of TdP, and that there is a possibility that dexmedetomidine may be torsadogenic, this effect is also worthy of investigation.
In sum, the use of dexmedetomidine is associated with many clinical benefits, but its effects on indices of myocardial repolarization, as well as its effects on glucose and potassium metabolism, remain poorly understood and need to be better defined in order to use this drug safely and effectively.
Objectives:
The primary objective of this study is to investigate the effects of three different doses of dexmedetomidine (0.25/0.5/0.75 mcg/kg) on indices of myocardial repolarization (QTc and Tp-e intervals). As a secondary objective, this study will also sample blood glucose and potassium levels before and after dexmedetomidine administration to ascertain if there is any significant effect of a single bolus dose on blood glucose concentrations.
Research Method:
The investigators propose a randomized, single-blinded, 4-group comparative study to characterize the effects of different doses of dexmedetomidine on myocardial repolarization and blood glucose levels in healthy children undergoing elective surgery. The study-specific interventions will include giving a bolus of dexmedetomidine (0.25/0.5/0.75 mcg/kg; or 10mL saline) after induction of general anesthesia, recording two 12-lead ECGs (one before and one after dexmedetomidine administration), and taking three venous blood samples (one before and two after dexmedetomidine administration) to measure glucose and potassium. If the anesthetist would like to administer dexmedetomidine to a participant in the control (saline) group as part of their normal practice, they can do so after the study period is over (after the last blood sample).
- Conditions
- Myocardial Repolarization, Healthy
- Being tested
- Dexmedetomidine, Saline
- Keywords
- changes in myocardial repolarization in healthy children
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
SalineDrug
Also called 9% NaCl
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine 0.25mcg/kg | Experimental | 0.25mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. Receives: Drug: Dexmedetomidine |
| Dexmedetomidine 0.5mcg/kg | Experimental | 0.5mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. Receives: Drug: Dexmedetomidine |
| Dexmedetomidine 0.75mcg/kg | Experimental | 0.75mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. Receives: Drug: Dexmedetomidine |
| Saline bolus | Sham comparator | 10mL normal saline solution administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Myocardial Repolarization (QTc and TP-e Intervals) 1min After Intervention
Absolute QTc and TP-e values 1min after a bolus of dexmedetomidine or saline. Measured with 12-lead ECG.
Measured: 60 seconds post-intervention
Secondary outcomes (2)
Blood Glucose Levels at 15min and 30min Post-intervention
Blood glucose levels at 15 min and 30 min after a bolus of dexmedetomidine or saline. Measured from 1 mL venous blood sample with blood gas analyzer.
Measured: over 30 minutes post-intervention
Blood Potassium Levels at 15min and 30min Post-intervention
Blood potassium levels at 15 min and 30 min after a bolus of dexmedetomidine or saline. Measured from 1mL venous blood sample with blood gas analyzer
Measured: over 30 minutes post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2015 (estimated)
- Study startSep 2015
- Primary completionSep 2017
- Study completionDec 2017
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Myocardial RepolarizationStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Simon Whyte, University of British Columbia
- Investigators
- Simon Whyte, MBBS, FRCA, Principal investigator, BC Children's Hospital, Department of Anesthesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02353169
- Sponsor's protocol ID
- H14-03274
- Acronym
- DexmedQT
- Status last verified
- Oct 2019
- First submitted
- 23 Dec 2014
- Last updated
- 7 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Gorges M, Poznikoff AK, West NC, Brodie SM, Brant RF, Whyte SD. Effects of Dexmedetomidine on Blood Glucose and Serum Potassium Levels in Children Undergoing General Anesthesia: A Secondary Analysis of Safety Endpoints During a Randomized Controlled Trial. Anesth Analg. 2019 Oct;129(4):1093-1099. doi: 10.1213/ANE.0000000000004154.
PubMed 31008751Gorges M, Sherwin ED, Poznikoff AK, West NC, Brodie SM, Whyte SD. Effects of Dexmedetomidine on Myocardial Repolarization in Children Undergoing General Anesthesia: A Randomized Controlled Trial. Anesth Analg. 2019 Oct;129(4):1100-1108. doi: 10.1213/ANE.0000000000004135.
PubMed 30985379
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Dexmedetomidine on Myocardial Repolarization in Children
- ClinicalTrials.gov ID
- NCT02353169
- Acronym / sponsor ID
- DexmedQT / H14-03274
- Conditions
- Myocardial Repolarization, Healthy
- Keywords
- changes in myocardial repolarization in healthy children
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Sep 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 2 Feb 2015 (estimated)
- Results
- Posted 7 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dexmedetomidine is a sedative drug that is commonly used to improve calmness and reduce pain in children waking up after surgery. Some of the side effects of dexmedetomidine, such as a potential change in how the heart muscles contract and changes in blood sugar and potassium levels, are poorly understood. The current study aims to examine these changes directly in healthy children undergoing elective surgery by measuring the heart beats (with an electrocardiogram) and blood sugar and potassium at specific times before and after dexmedetomidine is given. The investigators aim to establish a better understanding of this drug's safety profile.
Detailed description
Purpose:
This study is being conducted to evaluate the effect of three different doses of dexmedetomidine (Precedex® , Hospira Healthcare) on myocardial repolarization, and blood glucose and potassium levels in children undergoing elective surgery.
Hypotheses:
The investigators hypothesize that administering a dexmedetomidine bolus will have some effect on myocardial repolarization, blood glucose, and potassium concentrations in a dose-dependent manner, whereas a saline bolus will not.
Justification:
Dexmedetomidine is a potent, centrally acting α-2 adrenoreceptor agonist with sympatholytic, sedative, amnestic, anxiolytic and analgesic effects, which properties make it popular for use in both pediatric anesthesia and intensive care. In 2013, dexmedetomidine was added to the "possible risk factor for torsades de pointes (TdP)" drug list on crediblemeds.org. Clinicians are currently advised to be vigilant about potential QT prolongation with dexmedetomidine, especially in patients with congenital long QT syndrome (LQTS). However, current evidence for dexmedetomidine-induced prolonged QT is sparse and somewhat contradictory, and the effect of dexmedetomidine on the Tp-e interval has yet to be reported in detail in adults or children. Another poorly defined pharmacodynamic effect of dexmedetomidine is its effect on blood glucose concentration. Theoretically, dexmedetomidine would be expected to cause hypoinsulinaemia and a resultant increase in blood glucose levels (hyperglycemia). Previous studies are in contrast to this however; with reports of hypoglycemia after large doses of the drug. Considering the use of dexmedetomidine in pediatric anesthesia, pediatric intensive care and its increasing use in the neonatal population, increased knowledge of the effect of dexmedetomidine on blood glucose would be valuable.
Finally, hypokalemia is listed as a treatment-emergent adverse event occurring in >2% of adult patients receiving dexmedetomidine in long-term intensive care unit sedation studies. The effect of dexmedetomidine on serum potassium levels in healthy children has yet to be elucidated. Given that hypokalemia increases the risk of TdP, and that there is a possibility that dexmedetomidine may be torsadogenic, this effect is also worthy of investigation.
In sum, the use of dexmedetomidine is associated with many clinical benefits, but its effects on indices of myocardial repolarization, as well as its effects on glucose and potassium metabolism, remain poorly understood and need to be better defined in order to use this drug safely and effectively.
Objectives:
The primary objective of this study is to investigate the effects of three different doses of dexmedetomidine (0.25/0.5/0.75 mcg/kg) on indices of myocardial repolarization (QTc and Tp-e intervals). As a secondary objective, this study will also sample blood glucose and potassium levels before and after dexmedetomidine administration to ascertain if there is any significant effect of a single bolus dose on blood glucose concentrations.
Research Method:
The investigators propose a randomized, single-blinded, 4-group comparative study to characterize the effects of different doses of dexmedetomidine on myocardial repolarization and blood glucose levels in healthy children undergoing elective surgery. The study-specific interventions will include giving a bolus of dexmedetomidine (0.25/0.5/0.75 mcg/kg; or 10mL saline) after induction of general anesthesia, recording two 12-lead ECGs (one before and one after dexmedetomidine administration), and taking three venous blood samples (one before and two after dexmedetomidine administration) to measure glucose and potassium. If the anesthetist would like to administer dexmedetomidine to a participant in the control (saline) group as part of their normal practice, they can do so after the study period is over (after the last blood sample).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine 0.25mcg/kg | Experimental | Drug: Dexmedetomidine0.25mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. |
| Dexmedetomidine 0.5mcg/kg | Experimental | Drug: Dexmedetomidine0.5mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. |
| Dexmedetomidine 0.75mcg/kg | Experimental | Drug: Dexmedetomidine0.75mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. |
| Saline bolus | Sham comparator | Drug: Saline10mL normal saline solution administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia. |
Who may qualify
- Ages
- 3 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- ASA Physical Status I-II
- Age 3 to 10yrs
- Elective surgical procedure requiring general anesthesia
- Use of dexmedetomidine acceptable to the staff anesthesiologist
- Un-premedicated
Key exclusion criteria (11 listed)
- Long QT syndrome (LQTS)
- Cardiac disease or rhythm abnormalities
- Family history of LQTS or abnormal cardiac conduction
- Currently taking medications known to prolong QT
- Currently taking medications known to predispose to hypokalemia
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 |
|---|---|---|
| DexmedetomidineAlso: Precedex | Drug | Dexmedetomidine 0.25mcg/kg, Dexmedetomidine 0.5mcg/kg, Dexmedetomidine 0.75mcg/kg |
| SalineAlso: 9% NaCl | Drug | Saline bolus |
Primary outcome
Myocardial Repolarization (QTc and TP-e Intervals) 1min After Intervention
Time frame: 60 seconds post-intervention
Absolute QTc and TP-e values 1min after a bolus of dexmedetomidine or saline. Measured with 12-lead ECG.
2 secondary outcomes
Blood Glucose Levels at 15min and 30min Post-intervention
Time frame: over 30 minutes post-intervention
Blood Potassium Levels at 15min and 30min Post-intervention
Time frame: over 30 minutes post-intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31008751Gorges M, Poznikoff AK, West NC, Brodie SM, Brant RF, Whyte SD. Effects of Dexmedetomidine on Blood Glucose and Serum Potassium Levels in Children Undergoing General Anesthesia: A Secondary Analysis of Safety Endpoints During a Randomized Controlled Trial. Anesth Analg. 2019 Oct;129(4):1093-1099. doi: 10.1213/ANE.0000000000004154.
- Derived from this study: PubMed 30985379Gorges M, Sherwin ED, Poznikoff AK, West NC, Brodie SM, Whyte SD. Effects of Dexmedetomidine on Myocardial Repolarization in Children Undergoing General Anesthesia: A Randomized Controlled Trial. Anesth Analg. 2019 Oct;129(4):1100-1108. doi: 10.1213/ANE.0000000000004135.
- Individual participant dataSharing planned: No
Related trials for Myocardial Repolarization
Not yet recruitingObservational study
Relation of Total Ischemic Time to Repolarization Indices and Their Impact on Outcomes Among STEMI Patients Undergoing Primary PCI
ST Elevation (STEMI) Myocardial Infarction of Other Sites, Repolarization Indices
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.
Simon Whyte, MBBS, FRCA principal investigator
BC Children's Hospital, Department of Anesthesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine and Saline in people with Myocardial Repolarization and Healthy, run by University of British Columbia at 1 site in Canada.
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 6 inclusion and 11 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 7 Oct 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 Canada. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Oct 2019). 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?
Myocardial Repolarization (QTc and TP-e Intervals) 1min After Intervention (time frame: 60 seconds post-intervention). 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 NCT02353169, which also lists 2 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 7 Oct 2019.