Baclofen to Prevent Agitation in Alcohol Addicted Patients in ICU

Alcoholism Clinical Trial

— BACLOREA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02723383
• Other study ID #: RC15_0036
• Status: Completed
• Phase: Phase 3
• Start date: June 27, 2016
• Est. completion date: August 14, 2019

Study information

• Verified date: January 2020
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: August 14, 2019
• Est. primary completion date: August 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Alcoholism

Intervention

Drug:
• BACLOFEN
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.
• PLACEBO
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.

Locations

Country	Name	City	State
France	CHU ANGERS - réanimation chirurgicale	Angers
France	CHU de Brest Réanimation Chirurgicale	Brest
France	CHU de Brest Réanimation Médicale	Brest
France	CHU de Caen Réanimation Médicale	Caen
France	CHD La Roche Sur YON	La Roche Sur Yon
France	CH Le Mans	Le Mans
France	Centre Hospitalier de Bretagne Sud Réanimation Polyvalente Lorient	Lorient
France	Chu Montpellier	Montpellier
France	CHU MONTPELLIER - Lapeyronie	Montpellier
France	CHU NANTES - réanimation chirurgicale	Nantes
France	CHU NANTES -réanimation médicale	Nantes
France	Hopital Saint Antoine	Paris
France	Chu Poitiers	Poitiers
France	Ch Cornouaille	Quimper
France	Chu Rennes	Rennes
France	CHR Saint Nazaire	Saint Nazaire
France	CHRU Tours Bretonneau	Tours
France	Chu Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

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