Effect of Minocycline on Delirium Incidence in Critically Ill Patients

Delirium is a disorder of consciousness characterized by an acute onset and fluctuating course of impaired cognitive functioning. It is associated with unfavorable outcomes in hospitalized patients, including longer hospital length of stay, need for subsequent institutionalization and higher mortality rates. Patients in the intensive care unit (ICU) under mechanical ventilation and older age are at higher risk for the development of delirium. Several studies suggest that minocycline, through its anti-inflammatory effect, was able to prevent neuronal dysfunction in different models of ICU-related diseases. Thus, the present study aimed to evaluate the effect of minocycline on delirium development in critically ill patients. Patients will be randomized into one of two groups: the intervention group that will receive 100mg of minocycline 2 times a day and the placebo group. Medication or placebo will be continued for 28 days or until ICU discharge (whichever occurs first). Delirium will be diagnosed by the CAM-ICU. Coma will be defined by the Richmond Agitation-Sedation Scale (RASS) score of -4 or -5 and biomarkers will be used as alternative outcomes related to the pathophysiology of the disease (IL-1, IL-6, IL-10, and BDNF).

Study Overview

• Status: Completed
• Conditions: Delirium; Coma
• Intervention / Treatment: Drug: Placebos; Drug: Minocycline

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • SC
    • Criciuma, SC, Brazil, 88801250
      • São José Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical or surgical patients,
• Over 18 years,
• Expected ICU stay of at least 2 days estimated by the attending intensivist,
• Agree to participate in the study

Exclusion Criteria:

• Delirium prior to inclusion,
• Diagnosis of Parkinson's disease
• Diagnosis of dementia,
• Alcohol abuse history,
• Acute neurological condition at admission
• History of psychiatric disease
• Use of antipsychotics
• Pregnant or breastfeeding women,
• Expectation of death within 2 days
• Hospitalized for exclusive palliative care
• Known allergy to minocycline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Minocycline; Minocycline 100 mg BID	Drug: Minocycline; Minocycline 100mg BID
PLACEBO_COMPARATOR: Placebo; Placebo capsules identical to experimental arm	Drug: Placebos; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium and subsyndromal delirium incidence during ICU stay	Number of patients with delirium	up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days in delirium during ICU stay	Number of days being in delirium	up to 28 days
Coma-delirium free days during ICU stay	Number of days free of coma or delirium	up to 28 days
Length of mechanical ventilation during ICU stay	Number of days in mechanical ventilation	up to 28 days
Length of ICU stay	Number of days in the ICU	up to 28 days
ICU mortality	Number of dead during ICU stay	up to 28 days
Hospital mortality	Number of dead during hospital stay	up to 90 days
Long-term quality of life measured by the 12-Item Short-Form Health Survey V2	Quality of life measured after hospital discharge	until 12 months after hospital discharge
Long-term cognitive dysfunction measured by Montreal Cognitive Assessment score	Cognitive function after hospital discharge	until 12 months after hospital discharge
Plasma levels of interleukin-6, interleukin-10, brain derived neural factor and S100-B	Inflammatory and brain derived plasma biomarker levels	At Day 1 and 3 of ICU stay, and hospital discharge
Long-term Post-Traumatic Stress Disorder measured by Impact of Event Scale-Revised	Post-Traumatic Stress Disorder symptoms after hospital discharge measured by the Impact of Event Scale-Revised ranging from 0 to 88, higher values indicate more severe symptoms	until 12 months after hospital discharge
Long-term depression and anxiety symptoms measured by Hospital Anxiety and Depression Scale	Depression and anxiety symptoms after hospital discharge measured by Hospital Anxiety and Depression Scale, ranging from 0 to 21, higher values indicate more severe symptoms	until 12 months after hospital discharge

Collaborators and Investigators

• Sponsor: Universidade do Extremo Sul Catarinense - Unidade Academica de Ciecias da Saude

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 30, 2020
• Primary Completion (ACTUAL): November 30, 2021
• Study Completion (ACTUAL): November 30, 2021

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (ACTUAL): January 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: intensive care unit; delirium; minocycline
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Anti-Infective Agents; Anti-Bacterial Agents; Minocycline
• Other Study ID Numbers: MinoDelirium

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No