Dexmedetomidine Sublingual Film for the Management of Agitation in Delirium: Safety and Preliminary Efficacy
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Change in QTc Interval
研究概览
简要总结
The investigator will examine the safety, tolerability, optimal dose, and preliminary efficacy of dexmedetomidine sublingual film in a randomized, double-blind, controlled trial in 40 hospitalized patients with hyperactive delirium (i.e., delirium with agitation) in the Intensive Care Unit (ICU) setting.
Specific Aim #1 (safety and tolerability): To examine the incidence of cardiovascular and other side effects following the administration of dexmedetomidine sublingual film in patients hospitalized in the ICU with delirium and agitation in a randomized, double-blind trial (total N=80 patients with delirium [with or without agitation], with a goal of administering dexmedetomidine to at least 40 participants with agitation).
Hypothesis: Dexmedetomidine sublingual film will be associated with hypotension and/or bradycardia requiring clinical intervention in ≤ 20% (8 of 40) participants. Dexmedetomidine will not be associated with QTc prolongation or non-cardiac adverse events.
Specific Aim #2 (preliminary efficacy): To examine the impact of dexmedetomidine sublingual film on agitation and delirium severity.
Hypothesis: Dexmedetomidine will lead to reductions in agitation and delirium severity during the follow-up period (co-primary endpoints = 1 and 2 hours post-administration).
Specific Aim #3 (optimal dosing): To identify the minimum dose that is effective at reducing agitation and delirium severity without causing significant side effects.
Hypothesis: Participants receiving doses of 60 mcg of dexmedetomidine will have a faster time to a reduction in agitation and greater reductions in delirium severity than participants receiving 20 mcg of dexmedetomidine.
详细描述
Study Intervention
Participants will be randomized to receive either 20 mcg or 60 mcg of dexmedetomidine sublingually. Participants will receive repeat dosing every 30 minutes for up to three additional doses, leading to maximum doses of 80 mcg and 240 mcg, respectively. Both investigators and clinicians will be blind to the participant's group, with only the study pharmacist aware of the dose of medication on the films.
Baseline monitoring: Following enrollment, the study team will record baseline measures of heart rate, blood pressure, and oxygen saturation. An electrocardiogram (ECG) will be performed, and agitation and delirium severity will be measured.
Medication administration: Dexmedetomidine sublingual film will be administered by the study physician or study nurse as per the manufacturer's instructions. Dexmedetomidine administration will be repeated every 30 minutes if the participant continues to have agitation and does not meet any cardiovascular stopping criteria.
Monitoring for side effects: Heart rate, blood pressure, oxygen saturation, use of supplemental oxygen, and use of pressors will be monitored continuously and recorded every 30 minutes for the 6 hours following the initial medication administration (baseline; Time 0). An ECG will be performed at 1.5, 3, 4.5, and 6 hours, and QTc will be calculated using the Fridericia formula. Study staff will also monitor the participant and speak with nursing staff at 6 hours to assess for any other side effects/complaints the patient may have had during the time since medication administration.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults hospitalized on a medical or surgical intensive care unit at MGH
- •Diagnosis of delirium, assessed according to DSM-5 criteria (DSM-5)
- •Body mass index (BMI) between 18 and 30 kg/m2, inclusive, at screening
- •Weight at least 60 kg (132 pounds), at screening
- •In the opinion of the study and clinical teams, sufficiently physically healthy to receive dexmedetomidine sublingual film
排除标准
- •Per medical record or team report, diagnoses of:
- •Significant traumatic brain injury
- •History of stroke, with persistent neurologic deficits
- •Presence of any of the following cardiovascular comorbidities
- •Sick sinus syndrome
- •A resting heart rate of < 55 beats per minutes or systolic blood pressure (BP) <100 mmHg or >160 mmHg or diastolic BP <70 mmHg or ˃ 95 mmHg at enrollment and prior to dosing.
- •Evidence of cardiac ischemia on a 12-lead electrocardiogram (ECG)
- •Corrected QT interval of > 450 msec
- •Presence of a permanent pacemaker device
- •Per medical record (notes, current medications, flowsheets):
- •Second degree (or greater) Atrioventricular (AV) block without a pacemaker
- •Known allergy or adverse reaction to dexmedetomidine
- •Current use of dexmedetomidine
- •Inability to take sublingual dexmedetomidine due to severe agitation, neurological impairment, nil per os (NPO) status, or other cause.
- •Hepatic impairment (liver function tests > 3 times the upper limit of normal)
- •Severe renal impairment (glomerular filtration rate (GFR) < 30 ml/min or on dialysis)
- •Weight < 60 kg
- •Pregnancy (in women; tested with serum or urine human chorionic gonadotropin [hCG])
- •Non-fluency in English
- •Prior enrollment in the study, with receipt of study medication, during the current or a previous hospitalization
研究组 & 干预措施
20 mcg
Participants randomized to the 20mcg group will receive 20mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 80mcg.
干预措施: Dexmedetomidine sublingual film (Drug)
60 mcg
Participants randomized to the 60mcg group will receive 60mcg of dexmedetomidine sublingual film every 30 minutes, if they continue to have agitation and do not meet any cardiovascular stopping criteria. The maximum dosing for this arm is 240mcg.
干预措施: Dexmedetomidine sublingual film (Drug)
结局指标
主要结局
Change in QTc Interval
时间窗: Baseline, Hour 1.5, Hour 3, Hour 4.5, Hour 6
An ECG will be performed intermittently over the 6 hour monitoring period, and QTc will be calculated using the Fridericia formula.
Self-reported Side Effects
时间窗: Hour 6
Incidence of side effects reported for dexmedetomidine in post-marketing surveillance
Change in Oxygen Saturation
时间窗: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Oxygen saturation will be assessed participant's Epic flowsheet or using the telemetry monitor/pulse oximter for the 6 hours following the initial medication administration.
Change in Heart Rate
时间窗: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Heart rate will be assessed participant's flowsheet or using the telemetry monitor for the 6 hours following the initial medication administration.
Change in Blood Pressure
时间窗: Baseline, Medication Administration (Hour 0), Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 5, Hour 5.5, Hour 6
Blood pressure will be assessed participant's flowsheet or using the telemetry monitor/automated blood pressure cuff for the 6 hours following the initial medication administration.
次要结局
- Change in Agitation(Baseline, Hour 0.5, Hour 1, Hour 1.5, Hour 2, Hour 2.5, Hour 3, Hour 3.5, Hour 4, Hour 4.5, Hour 6)
- Time to resolution of agitation(Hour 6)
- Change in Delirium Severity(Baseline, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6)
研究者
Jeff C. Huffman, MD
Director of the Cardiac Psychiatry Research Program
Massachusetts General Hospital