Completed

NCT Number: NCT03090620

Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome

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.

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Key information

Conditions

Anticholinergics Toxicity

Age range

10 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

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

Aurora, Colorado, 80045, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Physostigmine

Drug

Administration of physostigmine bolus followed by an infusion

Lorazepam

Drug

Administration of lorazepam bolus followed by normal saline infusion

Primary outcomes

Comparison of RASS Score Between Physostigmine and Lorazepam: Before Bolus

Time frame: Baseline, immediately before bolus

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert & calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.
Comparison of RASS Score Between Physostigmine and Lorazepam: After Bolus

Time frame: Immediately after bolus, up to 10 minutes post-Baseline

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert & calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.
Comparison of RASS Score Between Physostigmine and Lorazepam: 4 Hours

Time frame: 4 hours

Determine the effectiveness of physostigmine as compared with lorazepam for control of antimuscarinic agitation. Richmond Agitation Sedation Scores (RASS) will be compared throughout treatment protocol. The Richmond Agitation-Sedation Scale (RASS) measures sedation and agitation. Possible scores range from -5 (unarousable) to 0 (alert & calm) to +4 (combative). Scores closer to 0 indicate a better outcome for this measurement.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: Before Bolus

Time frame: Baseline, immediately before bolus

Determine the effectiveness of physostigmine as compared with lorazepam in the reversal of antimuscarinic delirium. Confusion Assessment Method for the ICU (CAM-ICU) scores will be evaluated throughout the study. This measurement is a dichotomous outcome ("yes" or "no" for presence of delirium is indicated rather than a score). The number of participants exhibiting delirium is reported.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: After Bolus

Time frame: Immediately after bolus, up to 10 minutes post-Baseline

Determine the effectiveness of physostigmine as compared with lorazepam in the reversal of antimuscarinic delirium. Confusion Assessment Method for the ICU (CAM-ICU) scores will be evaluated throughout the study. This measurement is a dichotomous outcome ("yes" or "no" for presence of delirium is indicated rather than a score). The number of participants exhibiting delirium is reported.
Comparison of the Effectiveness in Control of Delirium Between Physostigmine and Lorazepam: 4 Hours

Time frame: 4 hours

Determine the effectiveness of physostigmine as compared with lorazepam in the reversal of antimuscarinic delirium. Confusion Assessment Method for the ICU (CAM-ICU) scores will be evaluated throughout the study. This measurement is a dichotomous outcome ("yes" or "no" for presence of delirium is indicated rather than a score). The number of participants exhibiting delirium is reported.

Secondary outcomes

Safety and Effectiveness of Physostigmine Infusion in the Setting of Antimuscarinic Toxidrome.

Time frame: Up to 4 hours

Evaluation of clinical antimuscarinic symptoms, along with presence of any adverse effects, during the infusion to report tolerability, safety profile, and effectiveness of the infusion. the number of participants exhibiting adverse events will be reported, by type.

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Collaborators

American Academy of Clinical Toxicology

Registry information

Official study title

A Randomized Trial Comparing Physostigmine vs Lorazepam for Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome

Acronym: TAAT

Important dates

Study start: 2017
Primary completion: 2020
Study completion: 2020
First posted: Mar 27, 2017
Registry last updated: Aug 23, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.