Baclofen to Prevent Agitation in Alcohol Addicted Patients in ICU

Study Overview
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Brief Summary
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Background: Alcohol is the leading psychoactive substance consumed in France, with about 15 million regular consumers. The National institute on Alcohol Abuse and Alcoholism (NIAAA) considers alcohol abuse to be more than 14 units of alcohol a week for men and 7 units for women. The specific complication of alcoholism is the alcohol withdrawal syndrome. Its incidence reaches up to 30% and its main complications are Delirium Tremens, restlessness, extended hospital stay, higher morbidity, psychiatric and cognitive impairment. Without appropriate treatment, Delirium Tremens can lead to death in up to 50% of patients. Methods/Design: This prospective, randomised, controlled study versus placebo will be conducted in eighteen French intensive care units (ICU). Patients with an alcohol intake higher than the NIAAA threshold, under mechanical ventilation, will be included. The primary objective is to determine whether Baclofen is more efficient than placebo in preventing restlessness-related side effects in ICU. Secondary outcomes include mechanical ventilation duration, length of ICU stay, cumulative doses of sedatives and painkillers received within 28 days of ICU admission. Restlessness-related side effects are defined as unplanned extubation, Medical disposal removal, falling out of bed, ICU runaway, immobilisation device removal, self-aggression or towards medical staff. Daily doses of Baclofen/placebo will be guided by creatinine clearance assessment once a day. Discussion: Restlessness in alcoholic patients is a life-threatening issue in ICUs. BACLOREA is a randomised study assessing the capacity of Baclofen to prevent agitation in mechanically-ventilated patients. Enrolment of 314 patients will begin in June 2016 and is expected to end in December 2019.

Official Title
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Baclofen to Prevent Agitation in Alcohol Addicted Patients in ICU: Study Protocol for a Randomised Controlled Against Placebo Trial

Conditions
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Alcoholism

Intervention / Treatment
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* Drug: BACLOFEN
* Drug: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults from 18 to 80 years old with an estimated alcohol intake of: 14 units of alcohol per week during the month before hospitalisation for men aged 18 to 64 7 units of alcohol per week during the month before hospitalisation for women or men older than 65. AND Intubated, ventilated with an expected duration of mechanical ventilation> 24 hours at least Exclusion Criteria: Hospitalization > 7 days Baclofen administration before ICU admission (personal treatment or single administration) Pregnancy Porphyria Burned on ICU admission Personal treatment including Gamma-hydroxybutyric acid (Alcover/Xyrem) Recent stroke or subarachnoid haemorrhage or head trauma with radiological evidence Recent or old paraplegia or tetraplegia Cardiac arrest with resuscitation manoeuvres before or after ICU admission Contraindication to Enteral drug administration for longer than 24 hours Lack of social protection Hypersensitivity to Baclofen Coeliac disease Refractory epilepsy Dementia, schizophrenia, Bipolar disorder or severe depression. Parkinson's disease Health care limitation owing to pejorative prognosis Tracheotomy on ICU admission Patients under guardianship or trusteeship Patients already enrolled in interventional study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BACLOFEN<br>patient will receive baclofen caps | Drug: BACLOFEN<br>* Daily doses will be adapted to daily MDRD creatinine clearance from 150 to 50mg. On the day of randomisation, the patient will receive the full daily dose in a one-shot administration. Then daily doses will be divided into 3 intakes on the following days. During the mechanical ventilation period, the treatment will be administered via the nasogastric feeding tube. After extubation, the treatment will be administered either via the nasogastric tube or the oral route.<br>|
| Placebo Comparator: PLACEBO<br>patient will receive placebo caps (lactose) | Drug: PLACEBO<br>* Daily doses will be adapted to daily MDRD creatinine clearance from 150 to 50mg. On the day of randomisation, the patient will receive the full daily dose in a one-shot administration. Then daily doses will be divided into 3 intakes on the following days. During the mechanical ventilation period, the placebo will be administered via the nasogastric feeding tube. After extubation, the placebo will be administered either via the nasogastric tube or the oral route.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence (yes or no) of agitation-related adverse events | Occurrence (yes or no) of agitation-related adverse events during treatment/placebo administration with at least one sign out of the following: Unplanned extubation Medical disposal removal Falling out of bed ICU runaway Immobilization device removal Self-aggression or aggression towards medical staff. | at the end of treatment (22 days max) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event (yes or no) related to agitation |  | within 28 days of ICU admission | 
| Extubation failure defined as reintubation |  | within the next 48 hours after extubation | 
| Tracheotomy for failure of mechanical ventilation weaning during hospitalization |  | an average of 28 days | 
| Infections acquired in the ICU: Urinary infection, pneumonia, catheter infection or bacteraemia during hospitalization |  | an average of 28 days | 
| Total doses of sedatives and painkillers received in the ICU |  | within 28 days of ICU admission | 
| Riker Sedation -Agitation Scale (SAS) in the ICU |  | within 28 days of ICU admission | 
| Daily CIWA-Ar alcohol withdrawal score |  | during the week following extubation | 
| Duration of mechanical ventilation during hospitalization |  | an average of 28 days | 
| Ventilation free days (VFD) |  | at day 28 | 
| Length of ICU stay |  | within 90 days | 
| Length of total hospitalisation |  | within 90 days | 
| Death in ICU |  | at days 28 and 90 | 
| Death during hospital stay during hospitalization |  | within 90 days | 
| Number of adverse event (s) per patient occurring in ICU from Day 1 to Day 28 |  | until Day 28 | 
| Agitation requiring rapid intravenous or intramuscular administration of an hypnotic or neuroleptic (bolus) |  | until Day 28 | 
| Reintubation due to restlessness or withdrawal syndrome |  | until Day 28 | 
| Agitation and mortality in ICU at Day 28 |  | at Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcoholism, intensive care, Baclofen, restlessness, Delirium tremens, Alcohol withdrawal syndrome