Modafinil Versus Placebo for Hypoactive Delirium in the Critically Ill

Modafinil vs. Placebo for Hypoactive Delirium in the Critically Ill: A Randomized, Controlled Trial

This is a randomized, double-blind, placebo controlled study of 30 patients. Patients who qualify, as per the inclusion criteria (RASS greater than -3, less then +1, CAM positive, present gastric access) will either be given 200mg of modafinil or an identical, indistinguishable placebo. The placebo and study drug will be distributed by the hospital pharmacy. Once enrolled, each patient will be reassessed every morning to determine appropriateness for drug administration. If the RASS is less than -3 (i.e. comatose) or greater then 0 modafinil will not be given. He/she will then be assessed each morning thereafter. Due to the stimulant-like actions of modafinil, the drug will be administered only in the morning. Patients will be assessed for delirium at least twice a day; trained personnel using the Confusion Assessment Method (CAM) will do the assessment. Qualification for a delirium free day will be no positive CAM screens for 24 hours following drug administration. Additional data such as days on mechanical ventilation and progression to tracheotomy will also be collected hypothesizing that patients who take modafinil will have a shorter time to extubation therefore avoiding the need for a tracheotomy. Post-discharge from the unit, but within 48 hours, patients will be asked to participate in a survey (The Richards-Campbell Sleep Questionnaire (RCSQ) assessing their perception of daytime and nighttime sleepiness in the intensive care unit as well as their overall perception of rest. Their functional capacity will also be evaluated at this time and compared to their pre-morbid baseline. The hypothesis tested is that Modafinil restores sleep cycle synchrony in the ICU therefore increasing delirium free days and improving ICU outcomes.

Study Overview

• Status: Withdrawn
• Conditions: Delirium; Respiratory Failure
• Intervention / Treatment: Drug: Modafinil; Drug: Placebo

Detailed Description

Eligibility Criteria

Inclusion Criteria To be eligible for study entry, subjects must satisfy these main criteria

Inclusion criteria:

3.1 Inclusion Criteria

• Adult patients ≥ 18 yrs of age, < 76 yrs of age
• Admitted to MICU (3B and 3C) or SICU (8C, 8D, 11C)
• Surrogate present to provide informed consent when patient is not able
• RASS score of >-3, < +1
• CAM positive
• Enteral access

3.2 Exclusion Criteria:

• Recent MI (within past 2 weeks)
• High risk of dysrhythmias (i.e. bundle branch block, QT prolongation, class IV HF, implanted device)
• Unable to tolerate enteral medication
• History of stimulant induced mania/psychosis
• Pre-existing neurologic disease
• Patients transferred from outside hospital
• Pregnancy
• Alcohol withdrawal
• History of end stage liver disease (Childs-Pugh class B or worse)
• Prognosis considered hopeless (CMO)

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Adult patients ≥ 18 yrs of age, < 76 yrs of age
• Admitted to MICU (3B and 3C) or SICU (8C, 8D, 11C)
• Surrogate present to provide informed consent when patient is not able
• RASS score of >-3, < +1
• CAM positive
• Enteral access

Exclusion Criteria:

• Recent MI (within past 2 weeks)
• High risk of dysrhythmias (i.e. bundle branch block, QT prolongation, class IV HF, implanted device)
• Unable to tolerate enteric medication
• History of stimulant induced mania/psychosis
• Pre-existing neurologic disease
• Patients transferred from outside hospital
• Pregnancy
• Alcohol withdrawal
• History of end stage liver disease (Childs-Pugh class B or worse)
• Prognosis considered hopeless (CMO)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; normal saline	Drug: Placebo; similar appearing inert tablet
Active Comparator: Modafinil; Modafinil 200 mg qAM enterally for the duration the patient is confirmed to be in a hypoactive delirium to a maximum of 14 days.	Drug: Modafinil; 200 mg daily; Other Names: provigil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Decreased CAM positive days in the ICU	Up to 14 days of ICU stay

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of stay in the ICU	Up to 14 days of ICU stay

Other Outcome Measures

Outcome Measure	Time Frame
Patients perception of their sleep pattern in the ICU	Up to 14 days of ICU stay
Return to baseline activities of daily living (ADL's)	Up to 14 days of ICU stay
Amount of psychotropic medication co-administered	Up to 14 days of ICU stay

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Gerald L Weinhouse, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): July 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: December 19, 2013
• First Submitted That Met QC Criteria: January 3, 2014
• First Posted (Estimate): January 7, 2014

Study Record Updates

• Last Update Posted (Estimate): November 3, 2016
• Last Update Submitted That Met QC Criteria: November 2, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Respiratory Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: 2013P002105