Clinical trial NCT02723383: Baclofen to Prevent Agitation in Alcohol Addicted Patients in ICU
Official title: Baclofen to Prevent Agitation in Alcohol Addicted Patients in ICU: Study Protocol for a Randomised Controlled Against Placebo Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alcoholism
Keywords: alcoholism
intensive care
Baclofen
restlessness
Delirium tremens
Alcohol withdrawal syndrome
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2016-03-30
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Occurrence (yes or no) of agitation-related adverse events
timeFrame: at the end of treatment (22 days max)
Secondary outcomes:
measure: Adverse event (yes or no) related to agitation
timeFrame: within 28 days of ICU admission
measure: Extubation failure defined as reintubation
timeFrame: within the next 48 hours after extubation
measure: Tracheotomy for failure of mechanical ventilation weaning during hospitalization
timeFrame: an average of 28 days
measure: Infections acquired in the ICU: Urinary infection, pneumonia, catheter infection or bacteraemia during hospitalization
timeFrame: an average of 28 days
measure: Total doses of sedatives and painkillers received in the ICU
timeFrame: within 28 days of ICU admission
measure: Riker Sedation -Agitation Scale (SAS) in the ICU
timeFrame: within 28 days of ICU admission
measure: Daily CIWA-Ar alcohol withdrawal score
timeFrame: during the week following extubation
measure: Duration of mechanical ventilation during hospitalization
timeFrame: an average of 28 days
measure: Ventilation free days (VFD)
timeFrame: at day 28
measure: Length of ICU stay
timeFrame: within 90 days
measure: Length of total hospitalisation
timeFrame: within 90 days
measure: Death in ICU
timeFrame: at days 28 and 90
measure: Death during hospital stay during hospitalization
timeFrame: within 90 days
measure: Number of adverse event (s) per patient occurring in ICU from Day 1 to Day 28
timeFrame: until Day 28
measure: Agitation requiring rapid intravenous or intramuscular administration of an hypnotic or neuroleptic (bolus)
timeFrame: until Day 28
measure: Reintubation due to restlessness or withdrawal syndrome
timeFrame: until Day 28
measure: Agitation and mortality in ICU at Day 28
timeFrame: at Day 28
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU ANGERS - réanimation chirurgicale
city: Brest
country: France
facility: CHU de Brest Réanimation Chirurgicale
city: Brest
country: France
facility: CHU de Brest Réanimation Médicale
city: Caen
country: France
facility: CHU de Caen Réanimation Médicale
city: La Roche Sur Yon
country: France
facility: CHD La Roche Sur YON
city: Le Mans
country: France
facility: CH Le Mans
city: Lorient
country: France
facility: Centre Hospitalier de Bretagne Sud Réanimation Polyvalente Lorient
city: Montpellier
country: France
facility: CHU MONTPELLIER - Lapeyronie
city: Montpellier
country: France
facility: Chu Montpellier
city: Nantes
country: France
facility: CHU NANTES - réanimation chirurgicale
city: Nantes
country: France
facility: CHU NANTES -réanimation médicale
city: Paris
country: France
facility: Hopital Saint Antoine
city: Poitiers
country: France
facility: Chu Poitiers
city: Quimper
country: France
facility: Ch Cornouaille
city: Rennes
country: France
facility: Chu Rennes
city: Saint Nazaire
country: France
facility: CHR Saint Nazaire
city: Tours
country: France
facility: CHRU Tours Bretonneau
city: Tours
country: France
facility: Chu Tours
Study officials:
References:
citation: 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.
citation: 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.