PHENObarbital for the MANagement of Severe Acute ALcohol Withdrawal Syndrome (PHENOMANAL): a Prospective Randomized Feasibility Study.
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Safety: adverse event rate
研究概览
简要总结
Severe acute alcohol withdrawal syndrome is a potentially life-threatening condition characterized by agitation, confusion, abnormal heart rhythms and seizures. Typically, clinicians treat the symptoms of alcohol withdrawal with a class of medications known as benzodiazepines (e.g., Valium). These medications have a short duration of activity and require repeated administration, often every hour or less, to reduce the symptoms of alcohol withdrawal. Many patients suffer complications related to inadequate treatment of alcohol withdrawal (e.g., abnormal heart rhythms, aspiration, seizures) resulting in admission to an intensive care unit and prolonged hospital stay, all of which increase healthcare costs. Although alcohol withdrawal is common, especially among disadvantaged (e.g., homeless) patients, limited funding is available to advance the care of patients suffering from alcohol withdrawal. A safe and effective treatment for severe alcohol withdrawal would benefit patients and our healthcare system.
Phenobarbital is an inexpensive, commonly available medication that is typically used to treat seizures. A key advantage of phenobarbital is that its calming effect lasts for a long period of time and it can be given as a 'one-time-dose' intravenously, so that it both prevents and treats withdrawal symptoms and reduces the need for repeated benzodiazepines. Through better symptom control, phenobarbital is expected to reduce the costs and complications of alcohol withdrawal. At present, physicians rarely use phenobarbital for this purpose, and additional research is needed for this medication to become part of routine care in clinical practice.
The PHENOMANAL pilot trial will assess safety and whether clinicians can administer a single dose of phenobarbital intravenously, in addition to benzodiazepines, compared to benzodiazepines alone for treating patients with severe alcohol withdrawal. This information will inform the design of a larger clinical trial. For patients, the PHENOMANAL trial has the potential to revolutionize how patients suffering from severe alcohol withdrawal are treated. For society and the healthcare system, phenobarbital is expected to reduce the complications and costs associated with severe alcohol withdrawal.
详细描述
In a 39 patient, single-centre pilot trial of phenobarbital as an adjunctive treatment for severe acute alcohol withdrawal syndrome (AAWS), the PHENOMANAL trial will demonstrate the ability to recruit, consent, and randomize participants and adhere to the assigned treatment protocol with minimal loss to follow up and infrequent adverse events. This pilot trial will provide data and proof of feasibility in preparation to conduct a multicentre randomized controlled trial of phenobarbital as an adjunctive treatment for severe AAWS. Patients will be recruited from the Emergency Department, Intensive Care Unit, Medical Step-Up unit, and wards of Unity Health Toronto - St. Michael's Hospital, a quaternary care centre located in downtown Toronto, Canada.
Recruitment Patients will be identified by research personnel during daytime hours from Monday to Friday using a multi-modal approach. With the assistance of the hospital informatics department, personnel will collect a daily census of patients who have been started on symptom-triggered benzodiazepine therapy using the Clinical Institute Withdrawal Assessment (revised) (CIWA-Ar) protocol.
Consent The investigators will use a hybrid consent model. Whenever possible, consent will be obtained from the patient or his/her substitute-decision-maker (SDM) at the time of recruitment. In this instance, Research Coordinators will ask one of the members within the 'circle of care' (e.g., physician, nurse, respiratory technologist, social worker, etc) to ask for permission from patient or their SDM for a research coordinator to contact him/her about participation in research.
Randomization To conceal allocation, central randomization will be conducted by the Pharmacy Department of St. Michael's Hospital using a list of random treatment assignments created on www.randomize.net.
Intervention As soon as possible after randomization, patients will receive either a single intravenous (IV) dose of phenobarbital (7.5 mg per kg of ideal body weight, prepared in 250 ml D5W; n=26) or placebo (250 ml D5W; n=13).
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, Investigator)
盲法说明
To conceal allocation, central randomization will be conducted by the Pharmacy Department of Unity Health Toronto - St. Michael's Hospital using a list of random treatment assignments created on www.randomize.net.
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Alcohol withdrawal syndrome (regardless of admitting diagnosis).
- •Severe symptoms, as defined by a 'Clinical Institute for Withdrawal Assessment Adult revised' (CIWA-Ar) score of 16 or more, or delirium severe enough to prohibit assessment with the CIWA-Ar, or observed withdrawal seizures, in each case despite treatment with at least 60 mg of diazepam (or an equivalent dose of another benzodiazepine) in the previous 16 hours, regardless of route of administration..
- •Early alcohol withdrawal, broadly defined as the first 16 hours after the diagnosis of acute alcohol withdrawal has been made. The time of diagnosis will be taken to be the time of prescription of symptom-triggered benzodiazepine therapy ("CIWA protocol"), or the time of consultation to ICU/Emergency Department, Internal Medicine, or the Addictions Service (Psychiatry) for the management of alcohol withdrawal.
- •Anticipated need for hospitalization (i.e. admission to ICU, medical step-up unit, or wards).
排除标准
- •an alternate etiology for delirium thought to be more likely than alcohol withdrawal;
- •age <16 years;
- •pregnancy (positive assay for ßhCG). A urine assay or blood test will be performed for all women < 55 yrs;
- •current breastfeeding;
- •severe acute hepatitis (AST or ALT >500); liver failure (INR >2 not otherwise explained);
- •a presenting complaint of neurotrauma, brain mass, or intra-cranial bleed; abnormal cell count or gram stain on lumbar puncture (if performed);
- •strong clinical suspicion of recent co-ingestion of depressant drugs (e.g. opioids, toxic alcohols, gamma-hydroxy-butyrate);
- •hemodynamic instability (systolic blood pressure [SBP] < 90 mmHg);
- •history of barbiturate allergy;
- •history of porphyria;
- •history of myasthenia gravis;
- •inability to obtain IV access;
- •anticipated transfer to another centre;
- •stated intent to leave against medical advice;
- •active outpatient prescription for anti-retroviral therapy for HIV
- •active outpatient prescription for one of the following anti-epileptic drugs: valproic acid, phenytoin, carbamazepine, clobazam, lacosamide, lamotrigine, levetiracetam, topiramate, primidone, or phenobarbital.
- •active outpatient prescription for an anticoagulant medication with a significant metabolic interaction with phenobarbital (i.e. warfarin or apixaban).
- •active outpatient prescription for a monoamine oxidase inhibitor (e.g., phenelzine, selegiline, tranylcypromine, isocarboxazid)
- •renal failure, as defined by a creatinine clearance <10 mls/minute (as calculated by Cockcroft-Gault equation) and/or active receipt of renal replacement therapy (dialysis).
- •administration of IV or oral phenobarbital during the index admission prior to randomization.
研究组 & 干预措施
Phenobarbital
Patients will receive a single dose of phenobarbital (7.5 mg/kg of ideal body weight, IV) in addition to usual therapy.
干预措施: Phenobarbital Sodium (Drug)
Placebo
Patients will receive an inactive placebo (IV).
干预措施: Inactive placebo (Drug)
结局指标
主要结局
Safety: adverse event rate
时间窗: 18 months
The rates of severe adverse events, including aspiration events and endotracheal intubation, will be compared between treatment and placebo groups.
次要结局
- Protocol feasibility: recruitment rate(18 months)