Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium

Launched by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE · Apr 30, 2024

Keywords

ClinConnect Summary

This clinical trial is studying whether a medication called rivastigmine can help prevent the return of a serious condition known as antimuscarinic delirium (AMD) after initial treatment with another drug called physostigmine. AMD is caused by certain medications or chemicals that affect the brain and can lead to confusion and other dangerous symptoms. The researchers believe that rivastigmine, which works longer than physostigmine, may help keep patients stable and reduce the chances of AMD coming back.

To be eligible for the trial, participants must be at least 10 years old and have been diagnosed with AMD by a doctor. They should have received or be planned to receive physostigmine, which helps control their symptoms. Participants will be randomly assigned to receive either rivastigmine or a placebo (a non-active treatment) after their symptoms are under control. Throughout the trial, participants will be closely monitored for their health and response to the medications. This study may be important for improving treatment options for people experiencing AMD.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 10 years of age or older
• • Diagnosis of antimuscarinic delirium by history and physical examination, in the opinion of the treating attending toxicologist.
• • Treatment with physostigmine according to the local standard of care is planned or has been administered by the treating attending toxicologist and is acceptable to the patient's primary attending physician and surrogate decision maker.
• • Antimuscarinic delirium is reasonably controlled after initial physostigmine treatment, as determined by treating toxicologist on bedside physical examination. (Patients may begin the screening and enrollment process prior to physostigmine administration, but will not undergo final initiation of study treatment until after response to physostigmine has been confirmed).
• Exclusion Criteria:
• • Age less than 10 years at time of enrollment
• • Surrogate decision maker not available to provide informed consent for enrollment.
• • Patient is pregnant or a ward of the state.
• • Inability to safely tolerate oral medication, in the judgement of the treating attending physician.
• * Evidence of significant risk for serious cardiac or neurologic sequelae of antimuscarinic poisoning:
• • a. Any known or suspected seizure activity prior to enrollment b. QRS duration \>100 milliseconds on EKG at enrollment c. Any ventricular dysrhythmia prior to enrollment d. Respiratory failure of any etiology requiring endotracheal intubation e. Any hypotension at enrollment: i. Adults: systolic blood pressure (SBP) \<90 mmHg ii. Children ≥10: systolic blood pressure (SBP) \<90 mmHg, as per Pediatric Advanced Life Support (PALS) age-based cutoff for children 10 years of age or older3 f. Any administration of sodium bicarbonate, hypertonic saline, vasopressors, inotropes, antiarrhythmic agents, or intravenous lipid emulsion prior to enrollment.
• • g. Unacceptable risk of serious medical sequelae of antimuscarinic poisoning in the judgment of the treating attending toxicologist.
• * Evidence of significant risk of adverse effect of AChE-I:
• a.Bradycardia or risk of AChE-I induced bradycardia at enrollment: i. Adults: heart rate (HR) \<80 beats per minute ii. Children: heart rate below the median heart rate for age as proposed by Fleming et al.33:
• • 1. Ages 10-12: HR \<84 beats per minute 2. Ages 12-15: HR \<78 beats per minute 3. Ages 15-18: HR \<73 beats per minute b. Known or suspected seizure disorder. c. History of asthma or COPD or wheezing during index presentation d. Known or suspected physical obstruction of intestinal or urogenital tract i. Ileus and/or urinary retention due to antimuscarinic poisoning do not exclude patients from enrollment.
• • e. Known or suspected peptic ulcer disease.
• • Any known allergy or intolerance to rivastigmine or other AChEI.
• • Failure to achieve reasonable initial control of antimuscarinic delirium after physostigmine administration, as assessed by treating toxicologist on bedside physical examination.