Effect of Minocycline on Delirium Incidence in Critically Ill Patients

Study Overview
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Brief Summary
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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).

Official Title
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Effect of Minocycline on Delirium Incidence in Critically Ill Patients

Conditions
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Delirium, Coma

Intervention / Treatment
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* Drug: Minocycline
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo vs minocycline
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline<br>Minocycline 100 mg BID | Drug: Minocycline<br>* Minocycline 100mg BID<br>|
| Placebo Comparator: Placebo<br>Placebo capsules identical to experimental arm | Drug: Placebos<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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delirium, minocycline, intensive care unit