Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome

NCT ID: NCT03090620

Last Updated: 2021-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-30
• Study Completion Date: 2020-08-31

Brief Summary

Overdose of xenobiotics (antihistamines, antipsychotics, or Jimson Weed) with resulting antimuscarinic toxidrome is a common scenario in medical toxicology. The result of antagonism of muscarinic receptors is a constellation of signs and symptoms (toxidrome): mydriasis, decreased sweat, decreased bowel sounds, agitation, delirium, hallucinations, urinary retention, tachycardia, flushed skin and seizures. Two treatment options are physostigmine or benzodiazepines.

Although the antimuscarinic toxidrome occurs commonly, physostigmine has been used sparingly despite evidence of safety and efficacy. To demonstrate the utility and safety of physostigmine, the investigators propose a randomized clinical trial of physostigmine compared to benzodiazepine for antimuscarinic toxicity.

Conditions

Anticholinergics Toxicity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Physostigmine

Physostigmine 0.02 mg/kg IV bolus (max of 2 mg), which can be repeated at 10 minutes, followed by a 0.02 mg/kg/hr (max of 2 mg/hr) infusion for 4 hours.

Group Type: EXPERIMENTAL

Physostigmine

Intervention Type: DRUG

Administration of physostigmine bolus followed by an infusion

Lorazepam

Lorazepam 0.05 mg/kg IV bolus (max 2 mg), which can be repeated at 10 minutes if inadequate patient response, followed by a Normal Saline infusion for 4 hours.

Group Type: EXPERIMENTAL

Lorazepam

Intervention Type: DRUG

Administration of lorazepam bolus followed by normal saline infusion

Interventions

Physostigmine

Administration of physostigmine bolus followed by an infusion

Intervention Type: DRUG

Lorazepam

Administration of lorazepam bolus followed by normal saline infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age >=10 and < 18 years
• Present to the Emergency Department or Intensive Care Unit for an antimuscarinic toxidrome from either a pharmaceutical agent such as antihistamine overdose, or natural toxins or products such as Datura stramonium
• Antimuscarinic toxidrome will be defined with at least one central nervous system agitation effect (agitation, delirium, visual hallucinations, mumbling incomprehensible speech), and at least 2 peripheral nervous system adverse effect (mydriasis, dry mucus membranes, dry axillae, tachycardia, decreased bowel sounds).
• Patients will also be required to have a RASS score of +2 to +4 on initial assessment.

Exclusion Criteria

• History of seizures or seizure during acute clinical course
• History of asthma or wheezing during clinical course Bradycardia (Heart Rate <60)
• Concomitant use of atropine or choline ester or depolarizing neuromuscular blocker during present illness and hospital course
• Diabetes gangrene, known intestinal obstruction or urogenital tract, vagotonic state
• QRS interval > 120 ms on electrocardiogram
• Known to be pregnant at the time of enrollment
• Known ward of the state

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

American Academy of Clinical Toxicology

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George S Wang, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Anschutz Medical Campus, Children's Hospital Colorado

Aurora, Colorado, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

16-1730

Identifier Type: -

Identifier Source: org_study_id