Rivastigmine for Antimuscarinic Delirium

Anticholinergic Toxicity Clinical Trial

— RIVA-AM  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06382649
• Other study ID #: 202403051
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: July 2026

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: Kevin Baumgartner, MD
• Phone: 3142731109
• Email: baumgartner.k[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 42
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

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:

1. Richmond Agitation-Sedation Scale (RASS) of +1 or higher at the time of enrollment

2. 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:

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.

Related Conditions & MeSH terms

• Anticholinergic Toxicity
• Delirium

Intervention

Drug:
• Rivastigmine
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
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

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	American Academy of Clinical Toxicology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Duration of agitation and delirium	Total duration of time during which patient is experiencing agitation and delirium (defined and assessed as above)	Typically 8-36 hours after randomization
Secondary	Total amount of sedatives administered	Total amount of sedatives (antipsychotics, benzodiazepines, dexmedetomidine, propofol, fentanyl, ketamine) administered during the study period.	Typically 8-36 hours after randomization
Secondary	Use of sedative infusions	Any use of continuous sedative infusion (dexmedetomidine, benzodiazepine, propofol, fentanyl) during the study period.	Typically 8-36 hours after randomization
Secondary	Use of physical restraints	Any use of physical restraints during the study period	Typically 8-36 hours after randomization
Secondary	Disposition	Disposition to ICU, stepdown/intermediate care unit, or floor level of care	Typically 8-36 hours after randomization
Secondary	Time to medical clearance	Time from presentation to medical clearance by the toxicology consult service	Typically 8-36 hours after randomization
Secondary	Oversedation	Incidence of oversedation, defined as RASS lower than -2	Typically 8-36 hours after randomization
Secondary	Intubation	Incidence of intubation and mechanical ventilation during the study period	Typically 8-36 hours after randomization
Secondary	Seizure	Incidence of epileptic seizure during the study period	Typically 8-36 hours after randomization
Secondary	Gastrointestinal upset	Incidence of clinically significant gastrointestinal upset during the study period	Typically 8-36 hours after randomization
Secondary	Bradycardia	Incidence of any bradycardia (as defined using age-based heart rate cutoffs) during the study period	Typically 8-36 hours after randomization