Combination of Haloperidol and Magnesium for Delirium Prevention in Critically Ill Elderly

NCT ID: NCT06168773

Last Updated: 2023-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2023-11-04

Brief Summary

Objective: The aim of this randomized double blinded study is to investigate the effectiveness and safety of the prophylactic use of haloperidol with or without magnesium (Mg) for delirium in high risk elderly patients postoperatively.

Patients and methods: 135 patients aged ≥ 65< 80 years old with PRE-DELIRIC Score 50% or more (20) were admitted to the ICU non-intubated following major non cardiac surgeries randomized into 3 groups, Group I received 1 mg haloperidol intravenously 3 times daily and magnesium sulfate 4 g intravenous infusion (IVI) in 1st day (diluted in 50 ml D5W over 24 hours) then 2g IVI over 24 hours (diluted in 50 ml D5W over 24 hours) for 3 days, Group II received 1 mg haloperidol intravenously 3 times ,Group III received 1 mL 0.9% of sodium chloride intravenously 3 times daily. The primary outcome of the study will be the incidence of delirium.

Detailed Description

This prospective randomized double-blind placebo-controlled study will be conducted in Ain Shams university surgical ICU on 135 patients aged ≥ 65< 80 years old with PRE-DELIRIC Score 50% or more (20) who are admitted to the ICU non-intubated following major non cardiac surgeries and anticipated intensive care unit (ICU) stay of at least 2 days as estimated by the attending intensivist after the approval of the research ethical committee and obtaining patients' or patients ' relatives written informed consent.

The study medications are continued until ICU discharge or until delirium occurred. In the latter case, study medications are stopped, and patients could be treated with dexmedetomidine.

For delirium prevention non-pharmacological interventions are also implemented like early mobilization, improving patient circadian rhythm, noise reduction are parts of the daily ICU care.

Patients will receive fentanyl infusion for analgesia. Those patients achieving a RASS score of ± 1 or 0 are monitored daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). Patients are diagnosed with delirium if they have at least 1 positive CAM-ICU without RASS -4/-5 during a complete day. Clinicians collecting data on delirium are all experienced in delirium assessment using the CAM-ICU. All patients are screened at least three times daily, and more often if required.

Conditions

Delirium in Old Age

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Group I (number of patients = 45):

will receive 1 mg haloperidol intravenously 3 times daily and magnesium sulfate 4 g intravenous infusion (IVI) in 1st day (diluted in 50 ml D5W over 24 hours) then 2g IVI over 24 hours (diluted in 50 ml D5W over 24 hours) for 3 days postoperatively starting the first dose 2- 4 hours after surgery. If the first prophylactic dose is delayed for more than 4 hours post admission, patient is excluded from the study.

Group Type: EXPERIMENTAL

Haloperidol Injection

Intervention Type: DRUG

to evaluate the efficacy and safety of short-term intravenous combination of low-dose haloperidol and magnesium for delirium prevention in critically ill elderly patients after elective major surgery.

Group II (number of patients= 45):

will receive 1 mg haloperidol intravenously 3 times daily and 50 ml of D5W IVI infusion over 24 hours for 4 days postoperatively starting the first dose 2- 4 hours after surgery.

Group Type: EXPERIMENTAL

Haloperidol Injection

Intervention Type: DRUG

to evaluate the efficacy and safety of short-term intravenous combination of low-dose haloperidol and magnesium for delirium prevention in critically ill elderly patients after elective major surgery.

Group III (number of patients = 45)

will receive 1 mL 0.9% of sodium chloride intravenously 3 times daily and 50 ml of D5W IVI infusion for 4 days postoperatively starting the first dose 2- 4 hours after surgery.

Group Type: PLACEBO_COMPARATOR

Haloperidol Injection

Intervention Type: DRUG

to evaluate the efficacy and safety of short-term intravenous combination of low-dose haloperidol and magnesium for delirium prevention in critically ill elderly patients after elective major surgery.

Interventions

Haloperidol Injection

to evaluate the efficacy and safety of short-term intravenous combination of low-dose haloperidol and magnesium for delirium prevention in critically ill elderly patients after elective major surgery.

Intervention Type: DRUG

Other Intervention Names

Magnesium Sulphate

Eligibility Criteria

Inclusion Criteria

• PRE-DELIRIC Score 50% or more (20) who are admitted to the ICU non-intubated following major non cardiac surgeries and anticipated intensive care unit (ICU) stay of at least 2 days as estimated by the attending intensivist

Exclusion Criteria

• sustained RASS of -4/-5 during the complete ICU admission
• primary neurologic event/injury with GCS ≤ 9 during the first 48 hours of ICU
• delirium prior to inclusion, Parkinson disease, dementia, alcohol abuse, an acute neurological condition, history of a psychiatric disease and use of antipsychotic agents
• history of clinically relevant ventricular arrhythmia in the last 12 months, QTc time of at least 500 milliseconds
• recent MI or cardiac decompensation, 2nd or 3rd AV block
• Known allergy or intolerance to haloperidol or magnesium sulphate.
• 80 years or older, had a body weight of 50 kg or less, or had liver failure (serum bilirubin level >2.9 mg/dL) or serum creatinine level >150 μmol/L
• Intubated patients at the time of ICU admission.

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Dina Salah Eldin Mahmoud Badre

Associate Professor of Anesthesia

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

AinShams university hospitals

Cairo, , Egypt

Countries

Egypt

Other Identifiers

FMASU R168/2021

Identifier Type: -

Identifier Source: org_study_id