Using rivastigmine to prevent the return of antimuscarinic delirium

Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium After Initial Control With Physostigmine (RIVA-AP): a Randomized, Placebo-controlled Trial

This study is testing if the drug rivastigmine can help prevent the return of antimuscarinic delirium symptoms after initial treatment with another medication.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 10 Years and up
• Sex: All
• Sponsor: Washington University School of Medicine (Academic / other)
• Locations: 1 site (St Louis, Missouri)
• Trial ID: NCT06399679 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of rivastigmine in preventing the recurrence of antimuscarinic delirium (AMD) after initial treatment with physostigmine. AMD is a serious condition caused by medications that block muscarinic receptors, and while physostigmine can control symptoms, they often return. The study is designed as a randomized, placebo-controlled trial where participants will receive either rivastigmine or a placebo following their initial treatment. The goal is to determine if rivastigmine can provide longer-lasting relief from AMD symptoms compared to placebo.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 10 years and older who have been diagnosed with antimuscarinic delirium and have shown a response to initial treatment with physostigmine.

Not a fit: Patients who are under 10 years of age, pregnant, or unable to provide informed consent will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the recurrence of antimuscarinic delirium in patients, improving their overall recovery and safety.

How similar studies have performed: There have been recent case reports and small observational studies suggesting that rivastigmine may be effective, indicating potential success for this approach.

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.

Where this trial is running

St Louis, Missouri

• Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)

Study contacts

• Principal investigator: Kevin Baumgartner, MD — Washington University School of Medicine
• Study coordinator: Kevin Baumgartner, MD

Conditions Anticholinergic Toxicity