Rivastigmine for Antimuscarinic Delirium

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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
• Препарат 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

Первичные конечные точки

• Time to control of agitation and delirium [Срок оценки: Typically 8-36 hours after randomization]

Вторичные конечные точки (11)

• Duration of agitation and delirium [Срок оценки: Typically 8-36 hours after randomization]
• Total amount of sedatives administered [Срок оценки: Typically 8-36 hours after randomization]
• Use of sedative infusions [Срок оценки: Typically 8-36 hours after randomization]
• Use of physical restraints [Срок оценки: Typically 8-36 hours after randomization]
• Disposition [Срок оценки: Typically 8-36 hours after randomization]
• Time to medical clearance [Срок оценки: Typically 8-36 hours after randomization]
• Oversedation [Срок оценки: Typically 8-36 hours after randomization]
• Intubation [Срок оценки: Typically 8-36 hours after randomization]
• Seizure [Срок оценки: Typically 8-36 hours after randomization]
• Gastrointestinal upset [Срок оценки: Typically 8-36 hours after randomization]
• Bradycardia [Срок оценки: Typically 8-36 hours after randomization]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Washington University School of Medicine — St Louis

Идентификаторы

NCT: NCT06382649 · 202403051

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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