Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Time to Delirium Resolution
研究概览
简要总结
Delirium is the most often encountered psychiatric diagnosis in the general hospital, with incidence up to 85% in the intensive care unit (ICU) setting and with significant consequences on patients' morbidity and mortality. Currently, although not FDA approved, antipsychotics are often considered the first-line pharmacological treatment. However, there can be limitations to their use, including side effects or lack of efficacy. Valproic acid (VPA) is one of the alternatives at times used in such patients which from limited case series data appears to be helpful and tolerated. VPA can provide relief from agitation that poses a threat to the safety and recovery of the patient. Moreover, mechanistically it addresses the neurochemical and cellular abnormalities inherent in delirium (it has NMDA-antagonist, anti-dopaminergic, GABAergic,anti-inflammatory, anti-apoptotic, and histone deacetylase inhibitor properties, among others). The purpose of this study is to evaluate the efficacy and tolerability of the VPA in the first known to us randomized controlled trial.
详细描述
The investigators plan to investigate the efficacy and tolerability of scheduled VPA as compared to placebo with as needed basis (PRN) haloperidol (as a back-up in both arms) for treatment of hyperactive or mixed delirium. Patients will be randomized to scheduled VPA or placebo (normal saline) and both arms will have flexible PRN dosing of haloperidol. Thus, the investigators plan to learn the time to delirium resolution in patients treated with VPA versus placebo; percentage of patients responding to VPA versus placebo; tolerability of VPA versus placebo. If addition of scheduled VPA proves to shorten time to delirium resolution as compared to placebo, lead to less use of haloperidol, and/or have fewer side effects, it would provide a very important addition to our limited evidence-based repertoire of delirium treatment. Moreover, this pilot study would then pave the way for the bigger randomized control trial powered to detect its effect size.
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
- •patients 18 years of age and older
- •admitted to surgical ICU
- •diagnosed with hyperactive or mixed delirium
排除标准
- •hypoactive delirium
- •primary team does not think patient is appropriate to participate
- •no oral access (PO or NGT)
- •non-English speaking
- •contraindication to study medications
- •pregnant women or woman of child-bearing age not on documented contraception
- •QTc = or greater than 480
- •hepatic dysfunction
- •decreased platelets or platelet dysfunction
- •bleeding disorder, current major bleeding
- •history of NMS, epilepsy, or PD
- •diagnosis of schizophrenia, bipolar disorder or schizoaffective disorder
- •on warfarin or carbapenems
- •delirium due to alcohol withdrawal
- •treated with antipsychotics for more than 48 hours prior to study enrollment.
研究组 & 干预措施
Valproic Acid
- Start:
VPA PO/NGT 500 mg BID 2. If need to increase in 24 or more hours:
VPA 500 mg PO/NGT q am, 1000 mg PO/NGT QHS 3. If need to increase in 24 or more hours:
VPA 500 mg PO/NGT q am, 1500 mg PO/NGT QHS 4. If need to increase in 24 or more hours:
VPA 500 mg PO/NGT Q am, 2000 mg PO/NGT QHS
Rescue at all stages: HAL IV 2-5 mg Q4hr PRN
干预措施: Valproic Acid (Drug)
Valproic Acid
- Start:
VPA PO/NGT 500 mg BID 2. If need to increase in 24 or more hours:
VPA 500 mg PO/NGT q am, 1000 mg PO/NGT QHS 3. If need to increase in 24 or more hours:
VPA 500 mg PO/NGT q am, 1500 mg PO/NGT QHS 4. If need to increase in 24 or more hours:
VPA 500 mg PO/NGT Q am, 2000 mg PO/NGT QHS
Rescue at all stages: HAL IV 2-5 mg Q4hr PRN
干预措施: Haloperidol (Drug)
Placebo
Placebo: PO/NGT BID
Rescue: HAL IV 2-5 mg Q4hr PRN
干预措施: Placebo (Drug)
Placebo
Placebo: PO/NGT BID
Rescue: HAL IV 2-5 mg Q4hr PRN
干预措施: Haloperidol (Drug)
结局指标
主要结局
Time to Delirium Resolution
时间窗: Up to 5 days
Delirium resolution was defined as three negative Confusion Assessment Method (CAM) assessments, performed by nurses every 12 hours.
次要结局
- Side Effects From Medications(Up to 5 days)
- Use of as Needed Anti-psychotic Agent(Up to 5 days)
- Intensity of Delirium as Measured by the Intensive Care Delirium Screening Checklist (ICDSC) Delirium Severity Scale(Up to 5 days)
- Length of ICU Stay(During expected average hospitalization (of 1 month))
- Length of Hospital Stay(During expected average hospitalization (of 1 month))
研究者
Yelizaveta Sher
Clinical Assistant Professor
Stanford University