Rivastigmine to Prevent Recurrence of Antimuscarinic Delirium After Initial Control With Physostigmine (RIVA-AP): a Randomized, Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Incidence of AMD recurrence
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
- •Ages 12-15: HR <78 beats per minute
- •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.
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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.
干预措施: Rivastigmine (Drug)
结局指标
主要结局
Incidence of AMD recurrence
时间窗: Typically 8-36 hours after randomization
Incidence of AMD recurrence, as defined by the development of agitation (Richmond Agitation-Sedation Scale of +1 or higher) and delirium (Confusion Assessment Method for the ICU positive) after initial control of AMD with physostigmine.
次要结局
- Seizure(Typically 8-36 hours after randomization)
- Total amount of sedatives administered(Typically 8-36 hours after randomization)
- Use of physical restraints(Typically 8-36 hours after randomization)
- Time to medical clearance(Typically 8-36 hours after randomization)
- Gastrointestinal upset(Typically 8-36 hours after randomization)
- Duration of agitation and delirium(Typically 8-36 hours after randomization)
- Use of sedative infusions(Typically 8-36 hours after randomization)
- Disposition(Typically 8-36 hours after randomization)
- Bradycardia(Typically 8-36 hours after randomization)
- Oversedation(Typically 8-36 hours after randomization)
- Intubation(Typically 8-36 hours after randomization)
研究者
Kevin Baumgartner
Assistant Professor of Emergency Medicine
Washington University School of Medicine