Intranasal Dexmedetomidine vs Oral Triclofos Sodium for EEG in Children With Autism

Autistic Disorder Clinical Trial

Official title:

Intranasal Dexmedetomidine vs Oral Triclofos Sodium Sedation for Children With Autism Undergoing Electroencephalograms - A Randomized Controlled Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04270708
• Other study ID #: 0090-20-RMC
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: March 1, 2020
• Est. completion date: August 1, 2022

Study information

• Verified date: February 2020
• Source: Rabin Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Children with Autistic Spectrum Disorder (ASD) often undergo an Electroencephalography (EEG) as part of routine work up. These children present a challenge to successful EEG execution, due to a lack of co-operation, and thus, are often in need of sedation. Historically we have used orally administered, Triclofos Sodium (TFS) - pharmacologically and physiologically similar to chloral hydrate, for sedation in this age group. However success using this drug is limited to approximately 75% in those aged 5 years and above, and possibly lower in this age group when associated with a diagnosis of ASD. The medication is often poorly tolerated by the oral route, and involves patient agitation, spiting (with incomplete drug ingestion), and immediate vomiting upon administration. Recently we have introduced Intra-nasal Dexmedetomidine (IN DEX), with an initial impression of much improved drug acceptance and possibly improved efficacy over TFS.

We designed this pilot study, with the aim of comparing efficacy, tolerance of drug administration and adverse events between TFS and IN DEX, with the goal of generating initial results as well as feasibility of recruitment for a larger trial.

Description:

Study participants will be allocated, amongst patients invited for routine EEG monitoring in the hospitals EEG facility. All patients will be fasted on arrival, with a recommendation to awaken early on the day of the planned examination.

Patients aged 4yrs and above, with a diagnosis of ASD will be allocated and investigated for fulfillment of inclusion and exclusion criteria for study participation. The legal guardians of patients meeting study criteria will be approached for study participation consent. Patients declining consent will be treated with TFS as per current protocol. Patients for whom consent is attained will comprise the study group.

Study group patients will be randomized for treatment and stratified according to age groups:

4-7, 8-12, 12-18. Treatment will consist of 2 alternative pathways:

Oral Trichlofos Sodium (TFS) Pathway:

1. Initial Drug dose: Patients will be treated orally with 50mg/kg of TFS to maximum of 2000gr.

2. Failure to achieve sedate state 45 minutes after drug administration will enable an additional oral dose of 25mg/kg.

3. Patients failing to fall asleep following second drug dose will be regarded as treatment failure.

4. Rescue therapy according to physician's choice can be instituted (Dexmed or Neuleptil).

Intranasal Dexmedetomidine (IN DEX) Pathway:

1. Initial drug dose: Patients will be treated with IN 3mcg/kg of Dexmedetomidine to max dose of 150mcg. The drug will be delivered through MAD nasal atomizer.

2. Failure to achieve sedate state 45 minutes after drug administration will enable an additional dose of IN 1.5mcg/kg by MAD device.

3. Paitients failing to fall asleep following second drug dose will be regarded as treatment failure.

4. Rescue therapy according to physician's choice can be instituted (Neuleptil not recommended due to drug interactions).

All sedated children will be connected to monitoring including ECG chest leads in addition to oxygen pulse saturation monitoring.

Primary outcome assessment: Sedation depth by UMSS will be assessed by the EEG technician, who will be blinded to the drug used for sedation.

Secondary outcome assessment:

1. Satisfaction from sedation depth for completing exam by blinded technician on VAS score.

2. EEG motion artifact by interpreting neurologist, blinded to study drug on VAS score.

3. All other secondary outcomes from drug administration to discharge, including adverse events and needed interventions, will be documented by the nurse who is not blinded to administered drug.

4. ECG monitoring for determination of HR or arrhythmia

5. Assessing incidence of bradycardia, hypotension and their severity:

a. HR and BP age related normal value chart to be used as reference. b. Bradycardia and Hypotension determined in relation to lower normal value for age: i. Mild<10% decrease from normal value ii. Moderate 10-20% decrease from normal value iii. Severe >20% or signs of hemodynamic compromise

Ethics: This study is a comparison of two medications currently under routine use for performing sedated EEG's in our medical center. The study will be authorized by the Rabin Campus Helsinki Committee. Informed consent will be requested from the accompanying legal guardian.

Statistics: Based on our experience, we assume a 70% success rate for sedation using TFS and a 90% success rate for IN DEX. Using an alpha of 0.05 and 80% power, two groups of 62 patients would be needed, to demonstrate statistical significance.

This trial is planned as a pilot study aimed at assessing drug effects and recruitment rate, over a limited time period of up to 2 year, or up to 200 patiens (100 TFS + 100 IN DEX).

Randomization and age stratification: Patient allocation will be determined according to an age stratified randomization table. Patients will be stratified by 3 age groups: 4-7, 8-12, 12-18.

Funding: No funding has been allocated for this study. Study will be conducted using routine medications in current practice without additional cost.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: August 1, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 19 Years

Eligibility

Inclusion Criteria:

1. Children aged 4-18 yrs referred for an EEG under sedation..

2. A Neurologist derived diagnosis of Autistic Spectrum Disorder (ASD).

3. ASA 1 or 2

Exclusion Criteria:

1. Allergy to study drug

2. Congenital heart disease, bradycardia < 60 or know arrhythmia/AV block.

3. Vasoactive drugs or treatment for arterial HTN.

4. Known Renal dysfunction Creatinine Clearance < 30% or known Liver dysfunction (Elevated LFT's).

5. Concurrent Treatment with drugs know to interact with Dexmedetomidine:

1. Atipical Antipsychotics / Phenothiazines

2. Tricyclic anti-depressents

3. Lacosamide treatment - Antiepileptic.

4. PDE V inhibitors (Viagra)

5. Beta-blockers

6. Phenothiazines

7. First generation Anti-histamines

6. Significant rhinorrhea.

Related Conditions & MeSH terms

• Autistic Disorder

Intervention

Drug:
• Dexmedetomidine
Patients with Autism will be treated with intranasal Dexmedetomidine as a sedative for EEG
• Triclofos 100 MG/ML
Patients with Autism will be treated with oral Triclofos as a sedative for EEG

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Rabin Medical Center

References & Publications (18)

Baier NM, Mendez SS, Kimm D, Velazquez AE, Schroeder AR. Intranasal dexmedetomidine: an effective sedative agent for electroencephalogram and auditory brain response testing. Paediatr Anaesth. 2016 Mar;26(3):280-5. doi: 10.1111/pan.12851. — View Citation

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Fernandes ML, Oliveira WM, Santos Mdo C, Gomez RS. Sedation for electroencephalography with dexmedetomidine or chloral hydrate: a comparative study on the qualitative and quantitative electroencephalogram pattern. J Neurosurg Anesthesiol. 2015 Jan;27(1):2 — View Citation

Grissinger M. Chloral Hydrate: Is It Still Being Used? Are There Safer Alternatives? P T. 2019 Aug;44(8):444-459. — View Citation

Gumus H, Bayram AK, Poyrazoglu HG, Canpolat DG, Per H, Canpolat M, Yildiz K, Kumandas S. Comparison of Effects of Different Dexmedetomidine and Chloral Hydrate Doses Used in Sedation on Electroencephalography in Pediatric Patients. J Child Neurol. 2015 Ju — View Citation

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Kaplan E, Daka A, Weissbach A, Kraus D, Kadmon G, Milkh R, Nahum E. Triclofos Sodium for Pediatric Sedation in Non-Painful Neurodiagnostic Studies. Paediatr Drugs. 2019 Oct;21(5):371-378. doi: 10.1007/s40272-019-00346-6. Review. — View Citation

Keller R, Basta R, Salerno L, Elia M. Autism, epilepsy, and synaptopathies: a not rare association. Neurol Sci. 2017 Aug;38(8):1353-1361. doi: 10.1007/s10072-017-2974-x. Epub 2017 Apr 28. Review. — View Citation

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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 2 — View Citation

Liu H, Sun M, Zhang J, Tian Q, Yu Q, Liu Y, Yang F, Li S, Tu S. Determination of the 90% effective dose of intranasal dexmedetomidine for sedation during electroencephalography in children. Acta Anaesthesiol Scand. 2019 Aug;63(7):847-852. doi: 10.1111/aas — View Citation

Mason KP, Lubisch N, Robinson F, Roskos R, Epstein MA. Intramuscular dexmedetomidine: an effective route of sedation preserves background activity for pediatric electroencephalograms. J Pediatr. 2012 Nov;161(5):927-32. doi: 10.1016/j.jpeds.2012.05.011. Ep — View Citation

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Xie Z, Shen W, Lin J, Xiao L, Liao M, Gan X. Sedation effects of intranasal dexmedetomidine delivered as sprays versus drops on pediatric response to venous cannulation. Am J Emerg Med. 2017 Aug;35(8):1126-1130. doi: 10.1016/j.ajem.2017.03.021. Epub 2017 — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal Sedation Depth	Maximal Sedation Depth by the University of Michigan Sedation Scale (UMSS)	Within 90 minutes
Primary	Technician satisfaction from sedation	Technician Ability to complete exam in satisfactory fashion - VAS score	Within 90 minutes
Secondary	Neurologist satisfaction from EEG motion artifact	Neurologist satisfaction from EEG motion artifact - VAS score	Within 7 days
Secondary	Compliance with IN vs Oral Delivery	Compliance with IN vs Oral Delivery - Successful drug administration Y/N?	Immediate upon administration
Secondary	Resistance to drug administration (1-10 scale)	Resistance to drug administration (1-10 scale): Crying / spitting or Complete or Partial Rejection for TFS/IN DEX	Immediate upon administration
Secondary	Achieving sedation following single dose	Achieving sedation following single dose of Dexmed vs TFS	Within 45 minutes
Secondary	Achieving sedation following rescue dose	Achieving sedation following additional rescue dose of Dexmed vs TFS	within 90 minutes
Secondary	Sedation onset, duration and recovery periods	Sedation onset, duration and recovery periods	Within 4 hours.
Secondary	Adverse Events	Sedation associated adverse events	Within 4 hours.