Rivastigmine for Antimuscarinic Delirium

NCT06382649 | Suspended Phase 2 FDA Drug

• 1 other identifier: 202403051
• 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, the standard antidote for AMD, currently has very limited availability in the United States due to an interruption of production. Recent case reports and small observational studies suggest that rivastigmine might be useful in the treatment of AMD, but there is not direct prospective evidence comparing rivastigmine to physostigmine or supportive care. In order to investigate the effectiveness of rivastigmine, the investigators propose a randomized, placebo-controlled clinical trial of rivastigmine for AMD. The investigators hypothesize that patients treated with rivastigmine for antimuscarinic delirium will experience more rapid resolution of agitation and delirium than those treated with placebo.

Conditions

Anticholinergic Toxicity

Outcome Measures

Primary Outcomes (1)

• Time to control of agitation and delirium

  Time from study drug administration to control of agitation and delirium, as defined by a Richmond Agitation-Sedation Scale (RASS) of 0 or -1 and a negative Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). RASS and CAM-ICU will be assessed by trained study personnel at the patient's bedside every 2 hours until sustained recovery (defined as absence of agitation and delirium on four consecutive assessments).

  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.
• Reasonably likely to benefit from antidotal therapy for antimuscarinic delirium, as demonstrated by clinically significant agitation and delirium:
• Richmond Agitation-Sedation Scale (RASS) of +1 or higher at the time of enrollment
• Positive for delirium as defined by the Confusion Assessment Method for the ICU (CAM-ICU)

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.

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

Location

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

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 19, 2024
• First Posted: April 24, 2024
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

US (1)