BACLOREA: Baclofen to Prevent Agitation in Alcohol Addicted Patients in ICU

Sponsor

Nantes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02723383

Collaborator

(none)

314

Enrollment

Locations

Arms

37.6

Actual Duration (Months)

17.4

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcoholism	Drug: BACLOFEN Drug: PLACEBO	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

314 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 27, 2016

Actual Primary Completion Date :

Aug 14, 2019

Actual Study Completion Date :

Aug 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BACLOFEN patient will receive baclofen caps	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 Comparator: PLACEBO patient will receive placebo caps (lactose)	Drug: 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.

Arm

Intervention/Treatment

Experimental: BACLOFEN

patient will receive baclofen caps

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 Comparator: PLACEBO

patient will receive placebo caps (lactose)

Drug: 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.

Outcome Measures

Primary Outcome Measures

Occurrence (yes or no) of agitation-related adverse events [at the end of treatment (22 days max)]
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.

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	CHU ANGERS - réanimation chirurgicale	Angers	France
2	CHU de Brest Réanimation Chirurgicale	Brest	France
3	CHU de Brest Réanimation Médicale	Brest	France
4	CHU de Caen Réanimation Médicale	Caen	France
5	CHD La Roche Sur YON	La Roche Sur Yon	France
6	CH Le Mans	Le Mans	France
7	Centre Hospitalier de Bretagne Sud Réanimation Polyvalente Lorient	Lorient	France
8	CHU MONTPELLIER - Lapeyronie	Montpellier	France
9	Chu Montpellier	Montpellier	France
10	CHU NANTES - réanimation chirurgicale	Nantes	France
11	CHU NANTES -réanimation médicale	Nantes	France
12	Hopital Saint Antoine	Paris	France
13	Chu Poitiers	Poitiers	France
14	Ch Cornouaille	Quimper	France
15	Chu Rennes	Rennes	France
16	CHR Saint Nazaire	Saint Nazaire	France
17	CHRU Tours Bretonneau	Tours	France
18	Chu Tours	Tours	France