Baclofen to Prevent Agitation in Alcohol Addicted Patients in ICU (BACLOREA)

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

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.

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.

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.

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.

Infections acquired in the ICU: Urinary infection, pneumonia, catheter infection or bacteraemia during hospitalization

Agitation requiring rapid intravenous or intramuscular administration of an hypnotic or neuroleptic (bolus)

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

Vourc'h M, Garret C, Gacouin A, Lacherade JC, Jonas M, Klouche K, Ferrandiere M, Jaber S, Flet L, Dailly E, Pouplet C, Maamar A, Reignier J, Roquilly A, Feuillet F, Mahe PJ, Asehnoune K; BACLOREA study group. Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2021 Feb 23;325(8):732-741. doi: 10.1001/jama.2021.0658.

Vourc'h M, Feuillet F, Mahe PJ, Sebille V, Asehnoune K; BACLOREA trial group. Baclofen to prevent agitation in alcohol-addicted patients in the ICU: study protocol for a randomised controlled trial. Trials. 2016 Aug 19;17(1):415. doi: 10.1186/s13063-016-1539-2.