Lorazepam for Delirium Prevention in Critically Ill Patients With High Anttila-Index (LOC2DEL)

Preventive Administration of Lorazepam in Critically Ill Patients With High Anttila-Index to Reduce the Incidence of Intensive Care Delirium: a Single-centre, Randomized, Controlled Clinical Trial - the Basel LOC2DEL-Trial

Delirium is a neuropsychiatric syndrome characterized by cognitive and attentional deficits, circadian rhythm, emotional and psychomotor dysregulation.

It is frequently encountered in patients admitted to an Intensive Care Unit (ICU) with a prevalence of 20-80% and associated with higher morbidity and mortality, prolonged hospitalization and cognitive impairment after hospitalization.

Alcoholism is an important risk factor that favors the development of delirium and a common comorbidity in patients admitted to the ICU.

Patients with alcohol use disorders can develop a withdrawal syndrome after cessation of alcohol consumption. The most severe form of alcohol withdrawal is the alcohol withdrawal delirium, which is characterized by a profound state of confusion. Early recognition and treatment significantly diminish severe complications of alcohol withdrawal delirium, including mortality.

The common pharmacological prevention and therapy of alcohol withdrawal syndrome is the administration of benzodiazepines, which have the potential to prevent or mitigate alcohol withdrawal delirium.

In the ICU setting the diagnosis of alcoholism based on self-report can be unreliable and complicated by acute illness.

The Anttila-Index is a parameter calculated from the carbohydrate-deficient transferrin and the gamma-glutamyltransferase. It has a high sensitivity and specificity for excessive alcohol consumption. Therefore, the Anttila-Index of patients admitted to the ICU could help identify patients at risk for developing delirium due to alcoholism or due to alcoholism in combination with other risk factors.

Schreiber et al. recently (October 2023) found significantly higher Anttila-Index in patients with delirium on a medical ICU. The investigators postulate that this also applies to the patients admitted to the mixed (medical and surgical) ICU at the University Hospital Basel (USB), since surgery is an additional crucial risk factor for delirium development.

Hypothesis: ICU delirium can be reduced by careful preventive administration of lorazepam in patients admitted to the ICU with an Anttila-Index at or above the cutoff value of four.

Study Overview

• Status: Not yet recruiting
• Conditions: Delirium Confusional State
• Intervention / Treatment: Drug: Lorazepam 1 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Prof. Dr. med. M. Siegemund, MD; Phone Number: +41(0)613286414; Email: martin.siegemund@usb.ch
• Study Contact Backup: Name: PD Dr. med. A. Hollinger, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Emergency/unplanned admission to the ICU
• Age ≥ 18 years
• ICU stay ≤ 24 hours until first study intervention
• Hospital admission ≤ 24 hours before ICU admission
• Anttila-Index ≥ 4

Exclusion Criteria:

• Pre-existing delirium
• Admission diagnosis that requires the administration of benzodiazepines (e.g. epileptic seizure)
• Pre-existing therapy with benzodiazepines
• Women: Pregnancy or breastfeeding
• Sequelae of acute intoxication (drugs or alcohol) at time of inclusion
• Hypersensitivity, allergy, or other absolute contraindication to lorazepam
• Participation in another study with investigational drug within the 30 days preceding and during the present study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; same amount (ml) of an identical viscous, oily solution without any pharmacological activity intravenously administered every 6 hours for 3 days
Experimental: Lorazepam	Drug: Lorazepam 1 mg; 0.5-1mg intravenously administered every 6 hours for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of ICU delirium (yes/no)	until day 3 after first study intervention

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Confusion; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Benzodiazepinones; Lorazepam
• Other Study ID Numbers: LOC2DEL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No