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NCT Number: NCT06382649

Rivastigmine for Antimuscarinic Delirium

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.

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Key information

Age range

10 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location status: Recruiting

Location contact

Kevin Baumgartner

CONTACT

[email protected]

3142731109

Who can participate

Healthy volunteers accepted: No

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

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.
  • 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)

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:

  • 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.

Treatment and study plan

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

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

Primary outcomes

  1. Time to control of agitation and delirium

    Time frame: Typically 8-36 hours after randomization

    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).

Secondary outcomes

  1. Duration of agitation and delirium

    Time frame: Typically 8-36 hours after randomization

    Total duration of time during which patient is experiencing agitation and delirium (defined and assessed as above)

  2. Total amount of sedatives administered

    Time frame: Typically 8-36 hours after randomization

    Total amount of sedatives (antipsychotics, benzodiazepines, dexmedetomidine, propofol, fentanyl, ketamine) administered during the study period.

  3. Use of sedative infusions

    Time frame: Typically 8-36 hours after randomization

    Any use of continuous sedative infusion (dexmedetomidine, benzodiazepine, propofol, fentanyl) during the study period.

  4. Use of physical restraints

    Time frame: Typically 8-36 hours after randomization

    Any use of physical restraints during the study period

  5. Disposition

    Time frame: Typically 8-36 hours after randomization

    Disposition to ICU, stepdown/intermediate care unit, or floor level of care

  6. Time to medical clearance

    Time frame: Typically 8-36 hours after randomization

    Time from presentation to medical clearance by the toxicology consult service

  7. Oversedation

    Time frame: Typically 8-36 hours after randomization

    Incidence of oversedation, defined as RASS lower than -2

  8. Intubation

    Time frame: Typically 8-36 hours after randomization

    Incidence of intubation and mechanical ventilation during the study period

  9. Seizure

    Time frame: Typically 8-36 hours after randomization

    Incidence of epileptic seizure during the study period

  10. Gastrointestinal upset

    Time frame: Typically 8-36 hours after randomization

    Incidence of clinically significant gastrointestinal upset during the study period

  11. Bradycardia

    Time frame: Typically 8-36 hours after randomization

    Incidence of any bradycardia (as defined using age-based heart rate cutoffs) during the study period

Study contacts

Contact information is provided by the study sponsor or research team.

Kevin Baumgartner, MD

CONTACT

[email protected]

3142731109

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • American Academy of Clinical Toxicology

Registry information

Official study title

Rivastigmine for Antimuscarinic Delirium: a Randomized, Placebo-controlled Trial

Acronym: RIVA-AM

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Apr 24, 2024
Registry last updated
Jun 4, 2026

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.

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