Department of Emergency Medicine, Hennepin Healthcare, Minneapolis, MN.
Department of Emergency Medicine, University of Arkansas for Medical Sciences, Little Rock, AR.
Acad Emerg Med. 2019 May;26(5):559-566. doi: 10.1111/acem.13673. Epub 2019 Jan 15.
Acute agitation in the emergency department (ED) represents a danger to both patients and their caregivers. Medication is often needed, and few high-quality randomized trials have evaluated the optimal drugs for this vulnerable population. In the United States, as of 2017, randomized trials of drugs typically cannot be conducted under Waiver of Consent (46 CFR 45.116), and Exception From Informed Consent trials (21 CFR 50.24) are limited to life-threatening conditions, are onerous, and require filing an investigational new drug application with the FDA. We sought to conduct a randomized double-dummy trial of inhaled loxapine versus intramuscular haloperidol + lorazepam for acute agitation in the ED by obtaining consent in advance ("preconsent") in patients at risk of future agitation, allowing study drug administration up to 3 years later if the patient presented with acute agitation.
We sought to report the successful enrollment rate of patients preconsented at an earlier ED visit for this trial.
This was an analysis of patients age 18 to 64 with bipolar I disorder or schizophrenia preconsented for enrollment in the trial (clinicaltrials.gov, NCT02877108) conducted at a single urban academic center seeing approximately 60,000 patients per year. Eligible patients were assessed for capacity to consent by trained research associates, and informed consent was obtained at an ED visit for the possibility of administering drugs for agitation within the next 3 years. In the event the patient later presented to the ED and the attending physician deemed the patient required treatment for acute agitation, preconsent was confirmed and study drug would be administered.
Over 67 days, 1,461 patients were screened in the ED, 269 had bipolar I or schizophrenia, 194 of whom had a contraindication to inhaled loxapine leaving 75 eligible patients; preconsent was obtained in 43 patients. Four additional patients who had not preconsented were consented for the trial in real time (three by surrogate, one patient had capacity while agitated) resulting in a total of 47 consented patients. Of these 47, a total of 12 were later removed from the study: 10 patients had unrecognized exclusion criteria for inhaled loxapine, one preconsented patient contacted the investigators at a later date and asked to be removed, and one surrogate revoked consent immediately after providing it. Only two patients were successfully enrolled, neither by preconsent: one was enrolled via a surrogate the day of enrollment, and the other was mildly agitated and had capacity to consent. The remaining patient with a valid surrogate consent did not receive study medication.
Utilization of preconsent to enroll patients in a randomized trial of treatments for acute agitation in the ED requires substantial resources and may not be feasible.
急诊科（ED）的急性激越对患者及其护理人员都构成了危险。通常需要药物治疗，很少有高质量的随机试验评估了这种脆弱人群的最佳药物。在美国，截至 2017 年，根据《联邦法规》第 46 篇第 45.116 节规定，药物的随机试验通常无法在豁免同意（waiver of consent）下进行，而根据《联邦法规》第 21 篇第 50.24 节规定的豁免知情同意试验（Exception From Informed Consent trials）仅限于危及生命的情况，程序繁琐，并要求向 FDA 提交新药研究申请。我们试图通过在有未来激越风险的患者提前获得同意（“预同意”），在 ED 中进行吸入洛沙平与肌肉注射氟哌啶醇+劳拉西泮治疗急性激越的随机双盲试验，允许在患者出现急性激越后长达 3 年内给予研究药物。
我们旨在报告提前在 ED 就诊的患者参与该试验的成功入组率。
这是一项在单一城市学术中心进行的单臂分析，该中心每年约有 60,000 名患者，入组的患者为 18 至 64 岁的双相 I 型障碍或精神分裂症患者，预先同意参加该试验（clinicaltrials.gov，NCT02877108）。有资格的患者由经过培训的研究助理评估其同意能力，并在 ED 就诊时获得同意，以便在未来 3 年内有可能给予药物治疗激越。如果患者后来到 ED，主治医生认为患者需要治疗急性激越，将确认预同意，并给予研究药物。
在 67 天内，1461 名患者在 ED 接受了筛查，269 名患者患有双相 I 型障碍或精神分裂症，其中 194 名患者对吸入洛沙平有禁忌症，因此有 75 名符合条件的患者；有 43 名患者获得了预同意。另外 4 名未预同意的患者实时同意参加试验（3 名由代理人同意，1 名患者在激越时具有能力），因此共有 47 名同意的患者。在这 47 名患者中，共有 12 名患者后来被从研究中剔除：10 名患者因吸入洛沙平而被排除出研究，1 名预同意的患者后来联系了研究人员并要求退出，1 名代理人在提供同意后立即撤销了同意。只有 2 名患者成功入组，均未通过预同意：1 名通过代理人在入组当天入组，另 1 名患者轻度激越且有能力同意。另一位有有效代理人同意的患者未接受研究药物。
利用预同意在 ED 中为急性激越患者入组随机试验需要大量资源，可能不可行。
