Critical IllnessPhase 4NCT01050699
Sleep Intervention During Acute Lung Injury
A Phase 4 study testing Dexmedetomidine and Midazolam and Fentanyl in people with Critical Illness and Sleep, run by University of Arizona at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Critical Illness, Sleep, Acute Lung Injury
- What is being tested?
- Dexmedetomidine and Midazolam and Fentanyl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesUnited States
- Study dates
- Aug 2009to Jan 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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).
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Southern Arizona VA Health Care System
Tucson, Arizona, 85723
University Medical Center
Tucson, Arizona, 85724
About this study
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.
Read the detailed description
Critically ill patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) who receive mechanical ventilation can suffer from severe sleep disruption despite continuous sedative infusions. Sleep disruption, in turn, may activate the sympathetic nervous system and cause elevation of circulating inflammatory cytokines, which, in turn, may play a causative role in delirium and post-traumatic stress disorder through consolidation of unpleasant memories during awakenings from sleep. Currently, there is very little understanding of the inter-relationship between critical illness, sleep, and neuropsychological well-being, due to the lack of intervention-based trials that improve sleep during critical illness. The central purpose of this proposal is to study the short-term effects of sedation with sympatholysis (central α2 adrenergic agent) on sleep and inflammation in critically ill patients with ALI/ARDS. Sedation with sympatholysis will be achieved by a novel sleep-promoting agent with central α2 adrenergic properties. This FDA approved novel sedative agent, dexmedetomidine, has been shown to decrease delirium (an independent predictor of mortality) and decrease duration of mechanical ventilation and ICU stay in critically ill patients receiving mechanical ventilation (Riker et al, JAMA 2009;301:542-44 and Pandharipande et al, JAMA 2007;298:2644-53). We will undertake sleep studies and measure circulating inflammatory cytokines that modulate sleep in patients with ALI/ARDS randomized to receive two different sedation strategies: central α2 adrenergic sedative-analgesic (dexmedetomidine) versus a conventional sedation strategy (midazolam and fentanyl) in a randomized, double blind, cross-over study. Specific Aim 1: To assess the short-term effect of an α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS. 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. 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. Collectively, our study will identify whether sleep disruption in such patients can be minimized. In the long-term, this program of research will identify sedation practices that are least associated with adverse short- and long-term consequences of critical illness, and thereby ultimately help improve quality of life of patients surviving critical illness
- Being tested
- Dexmedetomidine, Midazolam and Fentanyl
- Keywords
- critical illness, sleep, polysomnography, inflammatory cytokines, dexmedetomidine, acute lung injury, acute respiratory distress syndrome, midazolam, fentanyl, cytokines
- Medical subject headings
- Critical Illness, Acute Lung Injury, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
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.
Midazolam and FentanylDrug
Also called Versed (Midazolam), Fentanyl Citrate Injection, USP (Fentanyl)
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.)
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine | Experimental | Dexmedetomidine plus saline Receives: Drug: Dexmedetomidine |
| Usual Care | Active comparator | Midazolam and Fentanyl Receives: Drug: Midazolam and Fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Specific Aim 1: To assess the short-term effect of an α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS.
Measured: 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.
Measured: 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.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2010 (estimated)
- Study startAug 2009
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Sairam Parthasarathy, University of Arizona
- Investigators
- Sairam Parthasarathy, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01050699
- Sponsor's protocol ID
- HSC# 09-0232-01
- Other IDs
- 1R01HL095748-01A1
- Status last verified
- Aug 2021
- First submitted
- 14 Jan 2010
- Last updated
- 4 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sleep Intervention During Acute Lung Injury
- ClinicalTrials.gov ID
- NCT01050699
- Acronym / sponsor ID
- HSC# 09-0232-01
- Keywords
- critical illness, sleep, polysomnography, inflammatory cytokines, dexmedetomidine, acute lung injury, acute respiratory distress syndrome, midazolam
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Aug 2009
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 15 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Critically ill patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) who receive mechanical ventilation can suffer from severe sleep disruption despite continuous sedative infusions. Sleep disruption, in turn, may activate the sympathetic nervous system and cause elevation of circulating inflammatory cytokines, which, in turn, may play a causative role in delirium and post-traumatic stress disorder through consolidation of unpleasant memories during awakenings from sleep. Currently, there is very little understanding of the inter-relationship between critical illness, sleep, and neuropsychological well-being, due to the lack of intervention-based trials that improve sleep during critical illness. The central purpose of this proposal is to study the short-term effects of sedation with sympatholysis (central α2 adrenergic agent) on sleep and inflammation in critically ill patients with ALI/ARDS. Sedation with sympatholysis will be achieved by a novel sleep-promoting agent with central α2 adrenergic properties. This FDA approved novel sedative agent, dexmedetomidine, has been shown to decrease delirium (an independent predictor of mortality) and decrease duration of mechanical ventilation and ICU stay in critically ill patients receiving mechanical ventilation (Riker et al, JAMA 2009;301:542-44 and Pandharipande et al, JAMA 2007;298:2644-53). We will undertake sleep studies and measure circulating inflammatory cytokines that modulate sleep in patients with ALI/ARDS randomized to receive two different sedation strategies: central α2 adrenergic sedative-analgesic (dexmedetomidine) versus a conventional sedation strategy (midazolam and fentanyl) in a randomized, double blind, cross-over study. Specific Aim 1: To assess the short-term effect of an α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS. 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. 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. Collectively, our study will identify whether sleep disruption in such patients can be minimized. In the long-term, this program of research will identify sedation practices that are least associated with adverse short- and long-term consequences of critical illness, and thereby ultimately help improve quality of life of patients surviving critical illness
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Experimental | Drug: DexmedetomidineDexmedetomidine plus saline |
| Usual Care | Active comparator | Drug: Midazolam and FentanylMidazolam and Fentanyl |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age range 18-85 (inclusive)
- Potential subjects receiving mechanical ventilation
- Potential subjects must have:
- 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).
Key exclusion criteria (14 listed)
- 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.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineAlso: PrecedexIntravenous 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. | Drug | Dexmedetomidine |
| Midazolam and FentanylAlso: Versed (Midazolam), Fentanyl Citrate Injection, USP (Fentanyl)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.) | Drug | Usual Care |
Primary outcome
Specific Aim 1: To assess the short-term effect of an α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS.
Time frame: 72 hours
2 secondary outcomes
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.
Time frame: 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.
Time frame: 48 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sairam Parthasarathy, MD principal investigator
University of Arizona
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine and Midazolam and Fentanyl in people with Critical Illness and Sleep, run by University of Arizona at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Specific Aim 1: To assess the short-term effect of an α2 adrenergic agent on sleep quality in critically ill patients with ALI/ARDS. (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2021.