A Practical, Pilot, Randomized, Controlled Trial of Valproate Alone or in Combination With Quetiapine for Severe COVID-19 Pneumonia With Agitated Delirium
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- Change from baseline RASS score of +3 or greater
研究概览
简要总结
The primary purpose of this research is to determine whether Valproate alone, and in combination with Quetiapine, lowers confusion and agitation in persons with severe Corona Virus Disease (COVID)19 pneumonia during weaning from the breathing machine (ventilator). Though Valproate and Quetiapine are often given to persons with severe confusion with agitation, the purpose of this small research study is specifically for: a) persons infected with COVID 2019 on a ventilator whose agitation is not responding to the usual medications (like dexmedetomidine), and b) to reduce the time persons are treated with dexmedetomidine, which requires continuous close monitoring in an ICU.
详细描述
This is a pilot feasibility study involving a randomized, single-blind, controlled comparison scheme examining the efficacy and safety of standard of care (n=10) combined with valproate alone, and in combination with quetiapine (N=10) , in order to reduce the magnitude of agitation associated with COVID 19 delirium as assessed by the RASS scale when weaning from a ventilator, and reduce need for dexmedetomidine as assessed by number of doses of dexmedetomidine administered.
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
- Double (Participant, Outcomes Assessor)
盲法说明
study rater/outcomes assessor and participant will be ignorant of the treatment arm pharmacist and investigator will be aware of the treatment arm
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
- •Signed Informed Consent Form by his or her legal/authorized representative
- •Age ≥ 18 years at time of signing Informed Consent Form
- •Ability to comply with the study protocol, in the investigator's judgement
- •Hospitalized with COVID-19 pneumonia confirmed with World Health Organization (WHO) criteria (including an RNA test of any specimen, e.g. respiratory, blood, urine, stool, other bodily fluid) and evidence by chest X-ray or CT scan
- •Fraction of inspired oxygen (Fi02) ≤ 0.40 and positive end-expiratory pressure (PEEP) ≤8 OR Fi02 ≤ 0.50 and PEEP ≤5
- •Fi02 and PEEP ≤ values of previous day
- •Patient has acceptable spontaneous breathing efforts (may decrease vent rate by 50% for 5 minutes to detect effort.)
- •No neuromuscular blocking agents or blockade.
- •RASS score initially at -3 ≤, rising to 3+ after initial attempt to wean from standard of care sedating medications
- •Other investigational interventions may be permitted
排除标准
- •Known severe allergic reactions to valproate or quetiapine
- •History of hepatic encephalopathy or end-stage liver disease (Childs-Pugh class B or worse)
- •Alcohol, or history of alcohol/substance dependence prior to admission
- •Hx of dementia
- •Treatment with an antipsychotic agent in the 30 days before ICU admission
- •Baseline QT duration corrected (QTc) interval ≥ 500 msecs
- •Pregnancy
- •Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
- •In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 X upper limit of normal (ULN) detected within 24 hours at screening or at baseline
- •Absolute neutrophil count (ANC) < 1000/microliter (uL) at screening and baseline
- •Platelet count < 50,000/uL at screening and baseline
- •Individuals < 18 (infants, children, teenagers)
- •Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgement, precludes the patient's safe participation in and completion of the study, e.g. active seizure disorder already receiving treatment with lamotrigine
- •Informed consent could not be obtained from the legally authorized representative.
研究组 & 干预措施
Standard of Care Only Group
Patients maintained with mechanical ventilation will be treated with standard of care after cessation of paralytic agents.
干预措施: Standard of Care (Other)
Treatment Arm Group
Patients maintained with mechanical ventilation will be treated with standard of care, plus Valproate on Days 1-7 after cessation of paralytic agents, and then augmented by the addition of Quetiapine beginning Days 3-7 if there are no improvement in RASS score.
干预措施: Valproate (Drug)
Treatment Arm Group
Patients maintained with mechanical ventilation will be treated with standard of care, plus Valproate on Days 1-7 after cessation of paralytic agents, and then augmented by the addition of Quetiapine beginning Days 3-7 if there are no improvement in RASS score.
干预措施: Quetiapine (Drug)
Treatment Arm Group
Patients maintained with mechanical ventilation will be treated with standard of care, plus Valproate on Days 1-7 after cessation of paralytic agents, and then augmented by the addition of Quetiapine beginning Days 3-7 if there are no improvement in RASS score.
干预措施: Standard of Care (Other)
结局指标
主要结局
Change from baseline RASS score of +3 or greater
时间窗: Baseline, Day 7
Richmond Agitation Sedation Scale (RASS) score ranges from +4 (combative) to 0 (alert \& calm) to -5 (unarousable).
次要结局
- Incidence of Treatment Emergent Adverse Events(Day 7)
- Total dose of dexmedetomidine administered(Day 7)
研究者
Dominique Musselman
Associate Professor
University of Miami