A Phase 4 interventional study of Dexmedetomidine and Saline in Myocardial Repolarization and Healthy, sponsored by University of British Columbia. Completed at 1 site in Canada. Open to participants aged 3 Years to 10 Years. Per ClinicalTrials.gov, last updated 2019-10-07.
Sponsored by University of British Columbia · Phase 4, Interventional, and Basic science
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.
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).
University of British Columbia is the lead sponsor of 1,310 studies on the registry; 253 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 1 (17%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
0.25mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia.
Drug: Dexmedetomidine
0.5mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia.
Drug: Dexmedetomidine
0.75mcg/kg dexmedetomidine diluted with normal saline in a 10mL syringe, administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia.
Drug: Dexmedetomidine
10mL normal saline solution administered intravenously over 60 seconds starting 3 minutes after induction of anesthesia.
Drug: Saline
Also known as: Precedex
Also known as: 9% NaCl
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.
Time frame: 60 seconds post-intervention
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.
Time frame: 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
Time frame: over 30 minutes post-intervention
| Milestone | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus |
|---|---|---|---|---|
| Started | 15 | 18 | 16 | 15 |
| Completed | 12 | 12 | 12 | 12 |
| Not completed | 3 | 6 | 4 | 3 |
| Withdrew: Qtc > 450 msec | 1 | 1 | 1 | 1 |
| Withdrew: Or team declined | 2 | 0 | 0 | 0 |
| Withdrew: Inhalational induction | 0 | 2 | 0 | 0 |
| Withdrew: Ecg data error | 0 | 3 | 2 | 2 |
| Withdrew: Pre-op medication | 0 | 0 | 1 | 0 |
Absolute QTc and TP-e values 1min after a bolus of dexmedetomidine or saline. Measured with 12-lead ECG.
| ms | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus |
|---|---|---|---|---|
| Tp-e Post-intervention | 67.8 ± 6.0 | 64.0 ± 10.0 | 64.3 ± 6.9 | 66.3 ± 5.9 |
| QTc Post-intervention | 395.9 ± 16.1 | 390.2 ± 24.0 | 395.4 ± 18.7 | 416.4 ± 23.3 |
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.
| mmol/L | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus |
|---|---|---|---|---|
| Glucose 15 minutes after intervention | 5.3 ± 0.7 | 5.6 ± 0.7 | 5.9 ± 0.7 | 4.9 ± 0.7 |
| Glucose 30 minutes after intervention | 5.0 ± 0.7 | 5.0 ± 0.7 | 5.5 ± 0.6 | 5.1 ± 0.7 |
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
| mEq/L | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus |
|---|---|---|---|---|
| Potassium 15 minutes after intervention | 3.8 ± 0.7 | 3.7 ± 0.2 | 3.8 ± 0.2 | 3.9 ± 0.4 |
| Potassium 30 minutes after intervention | 3.6 ± 0.3 | 3.6 ± 0.4 | 3.8 ± 0.2 | 3.8 ± 0.2 |
Collected over 30 minutes post-intervention. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dexmedetomidine 0.25mcg/kg | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) |
| Dexmedetomidine 0.5mcg/kg | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) |
| Dexmedetomidine 0.75mcg/kg | 0/16 (0%) | 0/16 (0%) | 0/16 (0%) |
| Saline Bolus | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) |
| Age, Categorical(Participants) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| <=18 years | 12 | 12 | 12 | 12 | 48 |
| Between 18 and 65 years | 0 | 0 | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| Median | 4.5 (3 to 6.2) | 4.5 (3.8 to 6.5) | 5 (3.8 to 6) | 4.5 (3 to 6) | 5 (3 to 6) |
| Sex: Female, Male(Participants) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| Female | 3 | 5 | 5 | 6 | 19 |
| Male | 9 | 7 | 7 | 6 | 29 |
| Race and Ethnicity Not Collected(Participants) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| Count of participants | — | — | — | — | 0 |
| Region of Enrollment(participants) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| Canada | 12 | 12 | 12 | 12 | 48 |
| Heart Rate (beats/min)(beats/min) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| Mean | 88.9 ± 17.8 | 85.7 ± 13.4 | 84.6 ± 12.2 | 80.7 ± 12.5 | 85.0 ± 14.0 |
| Corrected QT interval (ms)(ms) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| Mean | 404.9 ± 17.1 | 408.8 ± 15.2 | 409.5 ± 17.2 | 404.0 ± 24.1 | 406.8 ± 18.2 |
| Interval between the peak and the end of the ECG T wave (Tp-e)(ms) | Dexmedetomidine 0.25mcg/kg | Dexmedetomidine 0.5mcg/kg | Dexmedetomidine 0.75mcg/kg | Saline Bolus | Total |
|---|---|---|---|---|---|
| Mean | 66.7 ± 7.2 | 63.0 ± 9.4 | 62.8 ± 6.1 | 65.3 ± 5.2 | 64.4 ± 7.1 |
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University of British Columbia