Rivastigmine for Antimuscarinic Delirium
- Conditions
- Interventions
- Registration Number
- NCT06382649
- Lead Sponsor
- Washington University School of Medicine
- 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.
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- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 42
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10 years of age or older
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Diagnosis of antimuscarinic delirium by history and physical examination, in the opinion of the treating attending toxicologist.
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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)
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Age less than 10 years at time of enrollment
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Surrogate decision maker not available to provide informed consent for enrollment.
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Patient is pregnant or a ward of the state.
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Inability to safely tolerate oral medication, in the judgement of the treating attending physician.
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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.
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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.
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Any known allergy or intolerance to rivastigmine or other AChEI.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 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. Rivastigmine Rivastigmine 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.
- Primary Outcome Measures
Name Time Method Time to control of agitation and delirium 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...
- Secondary Outcome Measures
Name Time Method Disposition Typically 8-36 hours after randomization Disposition to ICU, stepdown/intermediate care unit, or floor level of care
Use of physical restraints Typically 8-36 hours after randomization Any use of physical restraints during the study period
Gastrointestinal upset Typically 8-36 hours after randomization Incidence of clinically significant gastrointestinal upset during the study period
Intubation Typically 8-36 hours after randomization Incidence of intubation and mechanical ventilation during the study period
Use of sedative infusions Typically 8-36 hours after randomization Any use of continuous sedative infusion (dexmedetomidine, benzodiazepine, propofol, fentanyl) during the study period.
Duration of agitation and delirium Typically 8-36 hours after randomization Total duration of time during which patient is experiencing agitation and delirium (defined and assessed as above)
Total amount of sedatives administered Typically 8-36 hours after randomization Total amount of sedatives (antipsychotics, benzodiazepines, dexmedetomidine, propofol, fentanyl, ketamine) administered during the study period.
Time to medical clearance Typically 8-36 hours after randomization Time from presentation to medical clearance by the toxicology consult service
Oversedation Typically 8-36 hours after randomization Incidence of oversedation, defined as RASS lower than -2
Seizure Typically 8-36 hours after randomization Incidence of epileptic seizure during the study period
Bradycardia Typically 8-36 hours after randomization Incidence of any bradycardia (as defined using age-based heart rate cutoffs) during the study period
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States