Intranasal Dexmedetomidine Versus Oral Midazolam as Premedication for Propofol Sedation in Pediatric Patients Undergoing Magnetic Resonance Imaging

Dexmedetomidine Clinical Trial

Official title:

Prospective, Randomized, Double-blind, Double-dummy, Active-controlled, Phase 3 Clinical Trial Comparing the Safety and Efficacy of Intranasal Dexmedetomidine to Oral Midazolam as Premedication for Propofol Sedation in Pediatric Patients Undergoing Magnetic Resonance Imaging

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05192629
• Other study ID #: CHUB-PED-MIDEX_MRI
• Status: Recruiting
• Phase: Phase 3
• Start date: March 9, 2022
• Est. completion date: July 31, 2023

Study information

• Verified date: March 2022
• Source: Brugmann University Hospital
• Contact: Denis Schmartz, MD
• Phone: +3224773996
• Email: denis.schmartz[@]huderf.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A magnetic resonance imaging (MRI) examination usually takes 30 to 45 minutes and requires the patient to remain perfectly still during the entire acquisition process to ensure quality. Children under 6 years of age are not very cooperative and sedation is required for this age group.

Currently, there are no specific recommendations for sedation for a paediatric MRI examination. In 2018, a retrospective study on the sedation protocol applied at Hôpital Universitaire des Enfants Reine Fabiola (H.U.D.E.R.F.) was conducted. In this protocol, premedication was done with oral midazolam and sedation with iterative boluses of propofol. This study concluded that the protocol in place was effective, but found that image acquisition during the procedure was interrupted in 25% of cases, largely due to involuntary movements of the child.

Preoperative stress can be emotionally traumatic for the child and may even extend beyond the perioperative period, hence the importance of premedication. For the most anxious children, non-pharmacological means of premedication are often not sufficient. Moreover, the literature shows that pharmacological premedication is useful in reducing parental separation anxiety and in facilitating induction of anaesthesia.

Midazolam is an effective premedication agent with some disadvantages (paradoxical reaction, low compliance of oral intake). Dexmedetomidine is a highly effective α-2 receptor agonist that can also be used as premedication according to the current literature. A report by the Pediatric Sedation Research Consortium (P.S.R.C.) shows that it has a safe profile and an incidence rate of serious adverse events of 0.36% in the paediatric population. Furthermore, administered intranasally, it is non-invasive, painless and has good bioavailability (over 80%).

The primary objective is to demonstrate the superiority of intranasal dexmedetomidine over oral midazolam as a premedication for bolus sedation of propofol in terms of the incidence of any event during the MRI procedure requiring temporary or permanent interruption of the examination.

The impact of dexmedetomidine on the amount of propofol administered and on the post-sedation period, the impact of external factors on the primary objective, the acceptance of intranasal premedication by the children and the quality of the MRI images will also be analyzed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: July 31, 2023
• Est. primary completion date: June 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 6 Years

Eligibility

Inclusion Criteria:

• Children of both sexes, aged 6 months to 6 years,

• ASA score I to IV,

• Requiring standard magnetic resonance imaging due to clinical condition, regardless of underlying pathology,

• Sedation performed by an anesthesiologist,

• Written informed consent in accordance with the ICH-GCP and local legislation prior to trial entry.

Exclusion Criteria:

• Contraindications to MRI (cardiac pacemaker, neurostimulator, ferromagnetic implant),

• Sedation carried out by a non-anesthesiologist,

• Emergency MRI,

• Presence of head trauma,

• Presence of nasal congestion or upper respiratory tract infection on the day of sedation,

• Multiple procedures during the same sedation (operating room, evoked potentials, etc.),

• Children with pathologies requiring airway safety,

• Any known allergic or hypersensitivity reaction to dexmedetomidine,

• Any known allergic or hypersensitivity reaction to benzodiazepines,

• Concomitant use of negative chronotropes, as Digoxine,

• Patient known with chronic respiratory failure or myasthenia,

• Patient known with anatomical abnormality of the airway, lung disease or sleep apnea syndrome

• Patient with known cardiac rhythm abnormality or cardio-vascular disease,

• Patient with known hepatic disorder or chronic kidney disease,

• Patient with hypotension or bradycardia on the day of the examination,

• Patient with a BMI > 97th percentile (which corresponds to overweight, including obesity).

Related Conditions & MeSH terms

• Dexmedetomidine
• Midazolam
• MRI
• Pediatric Sedation

Intervention

Drug:
• Dexmedetomidine
Premedication by intranasal dexmedetomidine
• Midazolam
Premedication by intranasal midazolam

Locations

Country	Name	City	State
Belgium	Hôpital Universitaire des Enfants Reine Fabiola	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Brugmann University Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (34)

Anttila M, Penttilä J, Helminen A, Vuorilehto L, Scheinin H. Bioavailability of dexmedetomidine after extravascular doses in healthy subjects. Br J Clin Pharmacol. 2003 Dec;56(6):691-3. — View Citation

Berkenbosch JW. Options and Considerations for Procedural Sedation in Pediatric Imaging. Paediatr Drugs. 2015 Oct;17(5):385-99. doi: 10.1007/s40272-015-0140-6. Review. — View Citation

Bhatt M, Kennedy RM, Osmond MH, Krauss B, McAllister JD, Ansermino JM, Evered LM, Roback MG; Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN). Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med. 2009 Apr;53(4):426-435.e4. doi: 10.1016/j.annemergmed.2008.09.030. Epub 2008 Nov 20. — View Citation

Cho JE, Kim WO, Chang DJ, Choi EM, Oh SY, Kil HK. Titrated propofol induction vs. continuous infusion in children undergoing magnetic resonance imaging. Acta Anaesthesiol Scand. 2010 Apr;54(4):453-7. doi: 10.1111/j.1399-6576.2009.02169.x. Epub 2009 Nov 23. — View Citation

Chorney JM, Kain ZN. Behavioral analysis of children's response to induction of anesthesia. Anesth Analg. 2009 Nov;109(5):1434-40. doi: 10.1213/ane.0b013e3181b412cf. Epub 2009 Aug 27. — View Citation

Coté CJ, Wilson S; AMERICAN ACADEMY OF PEDIATRICS; AMERICAN ACADEMY OF PEDIATRIC DENTISTRY. Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016. Pediatrics. 2016 Jul;138(1). pii: e20161212. doi: 10.1542/peds.2016-1212. — View Citation

Ghai B, Jain K, Saxena AK, Bhatia N, Sodhi KS. Comparison of oral midazolam with intranasal dexmedetomidine premedication for children undergoing CT imaging: a randomized, double-blind, and controlled study. Paediatr Anaesth. 2017 Jan;27(1):37-44. doi: 10.1111/pan.13010. Epub 2016 Oct 13. — View Citation

Gupta A, Dalvi NP, Tendolkar BA. Comparison between intranasal dexmedetomidine and intranasal midazolam as premedication for brain magnetic resonance imaging in pediatric patients: A prospective randomized double blind trial. J Anaesthesiol Clin Pharmacol. 2017 Apr-Jun;33(2):236-240. doi: 10.4103/joacp.JOACP_204_16. — View Citation

Gutmann A, Pessenbacher K, Gschanes A, Eggenreich U, Wargenau M, Toller W. Propofol anesthesia in spontaneously breathing children undergoing magnetic resonance imaging: comparison of two propofol emulsions. Paediatr Anaesth. 2006 Mar;16(3):266-74. — View Citation

Jun JH, Kim KN, Kim JY, Song SM. The effects of intranasal dexmedetomidine premedication in children: a systematic review and meta-analysis. Can J Anaesth. 2017 Sep;64(9):947-961. doi: 10.1007/s12630-017-0917-x. Epub 2017 Jun 21. Review. — View Citation

Jung SM. Drug selection for sedation and general anesthesia in children undergoing ambulatory magnetic resonance imaging. Yeungnam Univ J Med. 2020 Jul;37(3):159-168. doi: 10.12701/yujm.2020.00171. Epub 2020 Apr 17. — View Citation

Kim HJ, Shin WJ, Park S, Ahn HS, Oh JH. The sedative effects of the intranasal administration of dexmedetomidine in children undergoing surgeries compared to other sedation methods: A systematic review and meta-analysis. J Clin Anesth. 2017 May;38:33-39. doi: 10.1016/j.jclinane.2017.01.014. Epub 2017 Jan 15. Review. — View Citation

Kumar L, Kumar A, Panikkaveetil R, Vasu BK, Rajan S, Nair SG. Efficacy of intranasal dexmedetomidine versus oral midazolam for paediatric premedication. Indian J Anaesth. 2017 Feb;61(2):125-130. doi: 10.4103/0019-5049.199850. — View Citation

Leroy PL, Costa LR, Emmanouil D, van Beukering A, Franck LS. Beyond the drugs: nonpharmacologic strategies to optimize procedural care in children. Curr Opin Anaesthesiol. 2016 Mar;29 Suppl 1:S1-13. doi: 10.1097/ACO.0000000000000312. Review. — View Citation

Li BL, Zhang N, Huang JX, Qiu QQ, Tian H, Ni J, Song XR, Yuen VM, Irwin MG. A comparison of intranasal dexmedetomidine for sedation in children administered either by atomiser or by drops. Anaesthesia. 2016 May;71(5):522-8. doi: 10.1111/anae.13407. Epub 2016 Mar 3. — View Citation

Mahmoud M, Barbi E, Mason KP. Dexmedetomidine: What's New for Pediatrics? A Narrative Review. J Clin Med. 2020 Aug 24;9(9). pii: E2724. doi: 10.3390/jcm9092724. Review. — View Citation

Malviya S, Voepel-Lewis T, Tait AR, Merkel S, Tremper K, Naughton N. Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). Br J Anaesth. 2002 Feb;88(2):241-5. — View Citation

Mason KP, Park RS, Sullivan CA, Lukovits K, Halpin EM, Imbrescia ST, Cavanaugh D, Prescilla R, Fox VL. The synergistic effect of dexmedetomidine on propofol for paediatric deep sedation: A randomised trial. Eur J Anaesthesiol. 2021 May 1;38(5):541-547. doi: 10.1097/EJA.0000000000001350. — View Citation

Mason KP. Sedation trends in the 21st century: the transition to dexmedetomidine for radiological imaging studies. Paediatr Anaesth. 2010 Mar;20(3):265-72. doi: 10.1111/j.1460-9592.2009.03224.x. Epub 2009 Dec 10. Review. — View Citation

Mekitarian Filho E, Robinson F, de Carvalho WB, Gilio AE, Mason KP. Intranasal dexmedetomidine for sedation for pediatric computed tomography imaging. J Pediatr. 2015 May;166(5):1313-1315.e1. doi: 10.1016/j.jpeds.2015.01.036. Epub 2015 Mar 6. — View Citation

Nagoshi M, Reddy S, Bell M, Cresencia A, Margolis R, Wetzel R, Ross P. Low-dose dexmedetomidine as an adjuvant to propofol infusion for children in MRI: A double-cohort study. Paediatr Anaesth. 2018 Jul;28(7):639-646. doi: 10.1111/pan.13400. Epub 2018 Jun 7. — View Citation

Peng K, Wu SR, Ji FH, Li J. Premedication with dexmedetomidine in pediatric patients: a systematic review and meta-analysis. Clinics (Sao Paulo). 2014 Nov;69(11):777-86. doi: 10.6061/clinics/2014(11)12. Review. — View Citation

Petroz GC, Sikich N, James M, van Dyk H, Shafer SL, Schily M, Lerman J. A phase I, two-center study of the pharmacokinetics and pharmacodynamics of dexmedetomidine in children. Anesthesiology. 2006 Dec;105(6):1098-110. — View Citation

Radhika KP, Sreejit MS, Ramadas KT. Efficacy of midazolam as oral premedication in children in comparison to triclofos sodium. Indian J Anaesth. 2016 Jun;60(6):415-9. doi: 10.4103/0019-5049.183389. — View Citation

Rosen DA, Daume JT. Short duration large dose dexmedetomidine in a pediatric patient during procedural sedation. Anesth Analg. 2006 Jul;103(1):68-9, table of contents. — View Citation

Sadeghi A, Khaleghnejad Tabari A, Mahdavi A, Salarian S, Razavi SS. Impact of parental presence during induction of anesthesia on anxiety level among pediatric patients and their parents: a randomized clinical trial. Neuropsychiatr Dis Treat. 2017 Feb 20;12:3237-3241. doi: 10.2147/NDT.S119208. eCollection 2017. — View Citation

Sriganesh K, Saini J, Theerth K, Venkataramaiah S. Airway Dimensions in Children with Neurological Disabilities During Dexmedetomidine and Propofol Sedation for Magnetic Resonance Imaging Study. Turk J Anaesthesiol Reanim. 2018 Jun;46(3):214-221. doi: 10.5152/TJAR.2017.48285. Epub 2017 Nov 27. — View Citation

Sulton C, McCracken C, Simon HK, Hebbar K, Reynolds J, Cravero J, Mallory M, Kamat P. Pediatric Procedural Sedation Using Dexmedetomidine: A Report From the Pediatric Sedation Research Consortium. Hosp Pediatr. 2016 Sep;6(9):536-44. doi: 10.1542/hpeds.2015-0280. Epub 2016 Aug 11. — View Citation

Sun Y, Lu Y, Huang Y, Jiang H. Is dexmedetomidine superior to midazolam as a premedication in children? A meta-analysis of randomized controlled trials. Paediatr Anaesth. 2014 Aug;24(8):863-74. doi: 10.1111/pan.12391. Epub 2014 Mar 26. — View Citation

Talon MD, Woodson LC, Sherwood ER, Aarsland A, McRae L, Benham T. Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery. J Burn Care Res. 2009 Jul-Aug;30(4):599-605. doi: 10.1097/BCR.0b013e3181abff90. — View Citation

Tu Y, Liang Y, Xiao Y, Lv J, Guan R, Xiao F, Xie Y, Xiao Q. Dexmedetomidine attenuates the neurotoxicity of propofol toward primary hippocampal neurons in vitro via Erk1/2/CREB/BDNF signaling pathways. Drug Des Devel Ther. 2019 Feb 19;13:695-706. doi: 10.2147/DDDT.S188436. eCollection 2019. — View Citation

van Hoorn CE, Flint RB, Skowno J, Davies P, Engelhardt T, Lalwani K, Olutoye O, Ista E, de Graaff JC. Off-label use of dexmedetomidine in paediatric anaesthesiology: an international survey of 791 (paediatric) anaesthesiologists. Eur J Clin Pharmacol. 2021 Apr;77(4):625-635. doi: 10.1007/s00228-020-03028-2. Epub 2020 Oct 29. — View Citation

Wollin SR, Plummer JL, Owen H, Hawkins RM, Materazzo F. Predictors of preoperative anxiety in children. Anaesth Intensive Care. 2003 Feb;31(1):69-74. — View Citation

Yip P, Middleton P, Cyna AM, Carlyle AV. Non-pharmacological interventions for assisting the induction of anaesthesia in children. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD006447. doi: 10.1002/14651858.CD006447.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;7:CD006447. — View Citation

* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of bradycardia	Incidence of bradycardia (defined as a decrease of 2 standard deviations from normal for age, as described by the American Heart Association (AHA) in the Pediatric Advanced Life Support (PALS) manual, and which requires intervention by the anesthesiologist in charge of the patient to improve heart rate and cardiac output); expressed as percentage of patients	6 hours
Primary	Hypotension	Incidence of hypotension (defined as a systolic blood pressure below the 5th percentile for age, as described by the AHA in the PALS manual, and which requires intervention by the anesthesiologist in charge of the patient to improve blood pressure); expressed as percentage of patients	6 hours
Primary	Desaturation	Incidence of oxygen desaturation under 95% (defined as moderate if SpO2 is between 90 and 95%, severe if below 90%); expressed as percentage of patients	6 hours
Primary	Movements	Incidence of involuntary movements requiring intervention by the anesthesiologist in charge of the patient to deepen sedation; expressed as percentage of patients	6 hours