Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium

NCT06399679 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 202403052
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Antimuscarinic delirium (AMD) is a common and dangerous toxicology condition caused by poisoning by medications and other chemicals that block muscarinic receptors. Physostigmine is effective in reversing AMD but has a short duration of action, and patient commonly experience recurrence of AMD after initial control with physostigmine. Recent case reports and small observational studies suggest that rivastigmine, which has a longer duration of action than physostigmine, might be useful in the treatment of AMD. In order to investigate the effectiveness of rivastigmine in preventing recurrence of AMD after initial control with physostigmine, the investigators propose a randomized, placebo-controlled clinical trial of rivastigmine for AMD. The investigators hypothesize that patients treated with rivastigmine after initial control of AMD with physostigmine will experience less recurrence of antimuscarinic delirium than those treated with placebo.

Conditions

Anticholinergic Toxicity

Outcome Measures

Primary Outcomes (1)

• Incidence of AMD recurrence

  Incidence of AMD recurrence, as defined by the development of agitation (Richmond Agitation-Sedation Scale of +1 or higher) and delirium (Confusion Assessment Method for the ICU positive) after initial control of AMD with physostigmine.

  Typically 8-36 hours after randomization

Secondary Outcomes (11)

• Duration of agitation and delirium

  Typically 8-36 hours after randomization

• Total amount of sedatives administered

  Typically 8-36 hours after randomization

• Use of sedative infusions

  Typically 8-36 hours after randomization

• Use of physical restraints

  Typically 8-36 hours after randomization

• Disposition

  Typically 8-36 hours after randomization

Study Arms (2)

Rivastigmine

EXPERIMENTAL

Patients in the rivastigmine arm will receive rivastigmine 3mg by mouth once, followed by rivastigmine 1.5mg by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for up to three doses.

Drug: Rivastigmine

Placebo

PLACEBO COMPARATOR

Patients in the placebo arm will receive oral placebo by mouth once, followed by oral placebo every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for up to three doses.

Drug: Placebo

Interventions

Rivastigmine DRUG

Rivastigmine 3mg by mouth once, followed by rivastigmine 1.5mg by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses

Rivastigmine

Placebo DRUG

Matching oral placebo by mouth once, followed by placebo by mouth every 1 hour as needed for ongoing delirium or agitation (at the discretion of the treating physician), for a maximum of three doses

Placebo

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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:
• \. 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• American Academy of Clinical Toxicology: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Interventions

Rivastigmine

Intervention Hierarchy (Ancestors)

Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Kevin Baumgartner, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin Baumgartner, MD

CONTACT

3142731109; baumgartner.k@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Emergency Medicine

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 6, 2024
• Study Start: November 4, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

US (1)