Sleep Intervention During Acute Lung Injury

NCT01050699 | Completed Phase 4 DMC

• 2 other identifiers: HSC# 09-0232-011R01HL095748-01A1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

The central purpose of this proposal is to study the short-term effects of sedation with sympatholysis, using α2 adrenergic agent Dexmedetomidine, on sleep and inflammation in critically ill patients with Acute Lung Injury and Acute Respiratory Disorder Syndrome (ALI/ARDS). An additional objective is to determine the effect of Dexmedetomidine sedation on the in-vitro production of sleep-modulating inflammatory cytokines by peripheral blood mononuclear cells of critically ill patients with ALI/ARDS.

Conditions

Critical Illness; Sleep; Acute Lung Injury; Acute Respiratory Distress Syndrome

Keywords

critical illness; sleep; polysomnography; inflammatory cytokines; dexmedetomidine; acute lung injury; acute respiratory distress syndrome; midazolam; fentanyl; cytokines

Outcome Measures

Primary Outcomes (1)

• Specific Aim 1: To assess the short-term effect of an α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS.

  72 hours

Secondary Outcomes (2)

• Specific Aim 2: To assess the short-term effect of an α2 adrenergic agent on sleep-modulating inflammatory cytokines in critically ill patients with ALI/ARDS.

  72 hours

• Specific aim 3: To determine the effect of α2 adrenergic agent on the in-vitro production of sleep-modulating inflammatory cytokines by peripheral blood mononuclear cells of patients with ALI/ARDS.

  48 hours

Study Arms (2)

Dexmedetomidine

EXPERIMENTAL

Dexmedetomidine plus saline

Drug: Dexmedetomidine

Usual Care

ACTIVE COMPARATOR

Midazolam and Fentanyl

Drug: Midazolam and Fentanyl

Interventions

Dexmedetomidine DRUG

Intravenous continuous infusion will be initiated with a (optional) loading dose of 1 mcg/Kg over 10 minutes followed by a maintenance infusion of 0.5 mcg/kg/hour for 24 hours.

Also known as: Precedex

Dexmedetomidine

Midazolam and Fentanyl DRUG

Midazolam (Versed): Loading dose 2-4 mg IV bolus followed by continuous infusion at 1-7 mg/hour. Open label aliquots for pain (Midazolam 1- 4 mg IV bolus.) Fentanyl: Loading dose 50-200 mcg IV bolus; Continuous infusion rate 50-300 mcg/hour. Open label aliquots for pain (Fentanyl 50 - 200 mcg IV bolus.)

Also known as: Versed (Midazolam), Fentanyl Citrate Injection, USP (Fentanyl)

Usual Care

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range 18-85 (inclusive)
• Potential subjects receiving mechanical ventilation
• Potential subjects must have:
• Acute hypoxemia with a PaO2/FiO2 \< 300 mm Hg (for ALI) OR \< 200 mm Hg (for ARDS),
• Bilateral infiltrates (including very mild infiltrates)
• No clinical evidence of left atrial hypertension, or a pulmonary artery wedge pressure \< 18 mm Hg.
• Potential subjects will be recruited after intubation and following a (systolic BP \> 90 mm Hg on 2 or less continuous infusion of pressors) and ventilatory parameters (requiring \< 60% fractional inspired O2 concentration \[FiO2\] and PEEP \< 8 cm H2O).

You may not qualify if:

• Acute myocardial infarction or unstable angina or active myocardial ischemia
• Potential subjects who are considered too unstable to undergo this investigation by their primary physician.
• Symptomatic bradycardia (ventricular rate \< 50 accompanied by hypotension \[Systolic blood pressure \< 90 mm Hg\] or atrio-ventricular block \[second degree type II or greater\]).
• Known inability to tolerate beta-blockers or dexmedetomidine.
• Systolic blood pressure \< 90 mmHg despite continuous infusions of 2 vasopressors before the start of study drug infusion.
• Potential subjects who are comatose or suffering from severe debilitating neurological disease (Intracerebral hemorrhage).
• History of severe dementia (derived from medical records or family sources).
• Active seizures
• Alcohol abuse by history
• Clinical evidence for decompensated congestive heart failure (elevated jugular venous distension, dependent edema) with echocardiographic evidence for significant systolic heart failure- left ventricular ejection fraction \<30%.
• Renal failure (on renal dialysis); Hepatocellular failure (Child-Pugh class C).
• Metastatic or terminal cancer and patients with do-not-resuscitate orders
• Pregnancy
• Potential subjects who are expected to be extubated within 48 hours

Sponsors & Collaborators

• University of Arizona: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Southern Arizona VA Health Care System

Tucson, Arizona, 85723, United States

Location

University Medical Center

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Critical Illness; Acute Lung Injury; Respiratory Distress Syndrome

Interventions

Dexmedetomidine; Midazolam; Fentanyl

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sairam Parthasarathy, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 14, 2010
• First Posted: January 15, 2010
• Study Start: August 1, 2009
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: August 4, 2021

Record last verified: 2021-08

Locations

US (2)