Rivastigmine for Antimuscarinic Delirium: a Randomized, Placebo-controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Time to control of agitation and delirium
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, 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.
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.
- •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)
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.
研究组 & 干预措施
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)
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)
结局指标
主要结局
Time to control of agitation and delirium
时间窗: 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 absence of agitation and delirium on four consecutive assessments).
次要结局
- Disposition(Typically 8-36 hours after randomization)
- Intubation(Typically 8-36 hours after randomization)
- Gastrointestinal upset(Typically 8-36 hours after randomization)
- Use of sedative infusions(Typically 8-36 hours after randomization)
- Use of physical restraints(Typically 8-36 hours after randomization)
- Duration of agitation and delirium(Typically 8-36 hours after randomization)
- Total amount of sedatives administered(Typically 8-36 hours after randomization)
- Time to medical clearance(Typically 8-36 hours after randomization)
- Oversedation(Typically 8-36 hours after randomization)
- Seizure(Typically 8-36 hours after randomization)
- Bradycardia(Typically 8-36 hours after randomization)
研究者
Kevin Baumgartner
Assistant Professor of Emergency Medicine
Washington University School of Medicine