Clinical trial NCT06399679: Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium
Official title: Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium After Initial Control With Physostigmine (RIVA-AP): a Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Anticholinergic Toxicity
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: American Academy of Clinical Toxicology
First posted: 2024-05-06
Enrollment: 42
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.
* 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).

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.
* Failure to achieve reasonable initial control of antimuscarinic delirium after physostigmine administration, as assessed by treating toxicologist on bedside physical examination.

Primary outcomes:
measure: Incidence of AMD recurrence
timeFrame: Typically 8-36 hours after randomization
Secondary outcomes:
measure: Duration of agitation and delirium
timeFrame: Typically 8-36 hours after randomization
measure: Total amount of sedatives administered
timeFrame: Typically 8-36 hours after randomization
measure: Use of sedative infusions
timeFrame: Typically 8-36 hours after randomization
measure: Use of physical restraints
timeFrame: Typically 8-36 hours after randomization
measure: Disposition
timeFrame: Typically 8-36 hours after randomization
measure: Time to medical clearance
timeFrame: Typically 8-36 hours after randomization
measure: Oversedation
timeFrame: Typically 8-36 hours after randomization
measure: Intubation
timeFrame: Typically 8-36 hours after randomization
measure: Seizure
timeFrame: Typically 8-36 hours after randomization
measure: Gastrointestinal upset
timeFrame: Typically 8-36 hours after randomization
measure: Bradycardia
timeFrame: Typically 8-36 hours after randomization
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Kevin Baumgartner, MD
role: PRINCIPAL_INVESTIGATOR
References: