Goal-Directed Sedation in Mechanically Ventilated Infants and Children

NCT04801589 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: HL151951R61HL151951
• Study Type: interventional
• Target: 372
• Locations: 1 country
• Sites: 1

Brief Summary

Ventilated pediatric patients are frequently over-sedated and the majority suffer from delirium, a form of acute brain dysfunction that is an independent predictor of increased risk of dying, length of stay, and costs. Universally prescribed sedative medications-the GABA-ergic benzodiazepines-worsen this brain organ dysfunction and independently prolong duration of ventilation and ICU stay, and the available alternative sedation regimen using dexmedetomidine, an alpha-2 agonist, has been shown to be superior to benzodiazepines in adults, and may mechanistically impact outcomes through positive effects on innate immunity, bacterial clearance, apoptosis, cognition and delirium. The mini-MENDS trial will compare dexmedetomidine and midazolam, and determine the best sedative medication to reduce delirium and improve duration of ventilation, and functional, psychiatric, and cognitive recovery in our most vulnerable patients-survivors of pediatric critical illness.

Conditions

Delirium; Critical Illness; Sedation Complication; Executive Dysfunction; Post Traumatic Stress Disorder

Keywords

pediatrics; critical care; agitation; sedation; delirium

Outcome Measures

Primary Outcomes (1)

• Daily prevalence of delirium

  The analysis of delirium prevalence will be conducted using a modified Intention-to-Treat (ITT) population, defined as all patients who were randomized and received study drug. The investigators chose a 14 day evaluation period for delirium, because it represents the best balance of gaining valuable clinical information, while maximizing resource utilization, given the average study drug infusion to be 5 days and maximum duration to be 10 days. Thus our follow-up period will cover 9 additional days of delirium monitoring after the study drug is stopped in the majority of our patients.

  14 days

Secondary Outcomes (10)

• Duration of mechanical ventilation (MV)

  14 days

• Incidence of long-term cognitive impairment.

  6 months post ICU discharge

• Incidence of post-traumatic stress symptoms in patients and parents/caregivers

  Baseline - 6 months post ICU discharge

• Functional status

  Baseline - 6 months post ICU discharge

• Markers of Inflammation, endothelial and blood brain barrier injury

  Days 1, 3, and 5

Study Arms (2)

Dexmedetomidine

ACTIVE COMPARATOR

Route and Concentration. The study drug will be administered intravenously (IV) by continuous infusion at concentrations of either 4 mcg/mL or 8 mcg/mL dexmedetomidine. Patients will only receive study drug while in the ICU and on mechanical ventilation, and thus will be monitored with continuous telemetry as per usual ICU practice. Dosing Range. Study drug dose will be titrated in a double-blind manner according to clinical effect to achieve a "goal" or "target" Richmond Agitation Sedation Score set by the managing clinical team. For patients in the dexmedetomidine group, dose will range from 0.2-2.0 mcg/kg/hr.

Drug: Dexmedetomidine

Midazolam

ACTIVE COMPARATOR

Route and Concentration. The study drug will be administered intravenously (IV) by continuous infusion at concentrations of either 0.5 mg/mL or 1 mg/mL midazolam. Patients will only receive study drug while in the ICU and on mechanical ventilation, and thus will be monitored with continuous telemetry as per usual ICU practice. Dosing Range. Study drug dose will be titrated in a double-blind manner according to clinical effect to achieve a "goal" or "target" Richmond Agitation Sedation Score set by the managing clinical team. For patients in the midazolam group, dose will range from 0.025-0.25 mg/kg/hr.

Drug: Midazolam

Interventions

Dexmedetomidine DRUG

For patients in the dexmedetomidine group, dose will range from 0.2-2.0 mcg/kg/hr. For example, a 10 kg patient on an infusion of 1 mcg/kg/hr of dexmedetomidine would receive 10 mcg of study drug per hour. This dose range have been selected after literature review and discussions with critical care practitioners, investigational pharmacists, and the mini-MENDS study steering committee.

Also known as: Precedex, Dexdor

Dexmedetomidine

Midazolam DRUG

For patients in the midazolam group, dose will range from 0.025-0.25 mg/kg/hr. For example, a 10 kg patient on an infusion of 0.15 mg/kg/hr of midazolam would receive 1.5 mg of midazolam per hour. This dose range have been selected after literature review and discussions with critical care practitioners, investigational pharmacists, and the mini-MENDS study steering committee.

Also known as: Versed, Hypnovel, Dormicum

Midazolam

Eligibility Criteria

• Age: 44 Weeks - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients will be eligible for enrollment if they are 1) aged 44 weeks post-menstrual age and up to 11 years, 2) planned admission to the pediatric ICU at Monroe Carell Jr. Children's Hospital at Vanderbilt (MCJCHV), and 3) requiring mechanical ventilation (MV) and sedation. Pre-pubescent children (\<11 years) are typically different from older children who often behave physiologically more similar to adults. Pre-pubescent children are more likely to be admitted to the PICU and are undergoing a steeper curve of neurocognitive maturation. Therefore, these patients may be at greatest risk for worse brain dysfunction.

You may not qualify if:

• Receiving continuous sedation for \> 72 hours prior to screening.
• Rapidly resolving respiratory failure at screening, with planned immediate liberation from MV.
• Severe developmental delay at baseline defined as a score of ≥ 4 (severe disability) on the Pediatric Cerebral Performance Category (PCPC) Scale, referencing cognitive status prior to critical illness.
• Clinically significant 2nd or 3rd degree heart block or bradycardia \< 60 beats per minute.
• Benzodiazepine dependency with ongoing medical requirement of continuous benzodiazepine (infusion).
• Inability to co-enroll with another study.
• Expected death or care plan for withdrawal of support measures within 24 hours of enrollment.
• Bilateral vision loss.
• Deafness that will preclude delirium evaluation.
• Documented allergy to either dexmedetomidine or midazolam.
• Medical requirement of continuous (infusion) neuromuscular blockade administration that is planned ongoing for at least 48 hours at time of screening.
• Attending physician refusal
• hour period of eligibility was exceeded before the patient was enrolled
• Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) refusal
• Legal Authorized Decision Maker (e.g. legal guardian/power of attorney) unavailable

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Pfizer: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

MeSH Terms

Conditions

Delirium; Critical Illness; Stress Disorders, Post-Traumatic; Psychomotor Agitation

Interventions

Dexmedetomidine; Midazolam

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Dyskinesias; Psychomotor Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Heidi Smith, MD, MSCI

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heidi Smith, MD, MSCI

CONTACT

(615) 936-6808; heidi.smith@vumc.org

Rebecca Abel, MA

CONTACT

(615) 875-3763; rebecca.abel@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: March 17, 2021
• Study Start: May 10, 2021
• Primary Completion: April 17, 2026
• Study Completion (Estimated): September 16, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 5 years following publication.
• Access Criteria: To achieve approved aims via email proposal to PIs.

Locations

US (1)