Mechanically Ventilated and Intubated SubjectsPhase 4NCT00216190

A Safety and Efficacy Study of Dexmedetomidine in ICU Patients Requiring Continuous Sedation

A Phase 4 study testing Dexmedetomidine HCL Injection and Midazolam Injection in people with Mechanically Ventilated and Intubated Subjects, run by Hospira, now a wholly owned subsidiary of Pfizer at 96 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the safety and efficacy of dexmedetomidine in ICU subjects who are initially intubated, mechanically ventilated and require sedation for beyond 24 hours. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Mechanically Ventilated and Intubated Subjects
What is being tested?: Dexmedetomidine HCL Injection and Midazolam Injection
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 420 participants
Where: 96 sitesin 5 countries
Study dates: Mar 2005to Aug 2007
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subject is ≥18 years of age.
If female, subject is non-lactating, and is either:
Not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
Of childbearing potential but is not pregnant as confirmed by negative serum pregnancy test at time of screening, and is practicing one of the following methods of birth control: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.
Subject is initially intubated and mechanically ventilated, or is planned for imminent intubation and mechanical ventilation, sedation is anticipated to be required during mechanical ventilation, and mechanical ventilation is anticipated to continue for at least 72 hours.
Subject or subject's legally authorized representative has voluntarily signed and dated an informed consent form, approved by the applicable Institutional Review Board (IRB), after the nature of the study has been explained and the subject or subject's legally authorized representative has had the opportunity to ask questions. The informed consent must be signed before any study specific procedures are performed.
Subject is sedated within a Richmond Agitation-Sedation Scale (RASS) range of -2 to +1 at the time of initiation of study drug

Who cannot join

Subject has been intubated for greater than 96 hours prior to the initiation of study drug (thus, the attainment of consent, screening evaluations, and randomization must all have been completed by the 96th hour post-intubation, so that the actual initiation of the study drug infusion may start by the end of the 96 hour window).
Subject has serious central nervous system pathology/trauma that, per clinical judgment of the Investigator, precludes responsiveness or survival.
Subject for whom opiates, benzodiazepines, or dexmedetomidine are contraindicated, or who has known or suspected serious allergy to any drug that might be administered during the course of the study.
Subject for whom alpha-2 agonists are contraindicated.
Subject requires neuromuscular blocking agents during the study for use other than intubation.
Subject requires epidural or spinal analgesia during the study.

Show all 25Show fewer

Subject meets any of the following cardiovascular criteria:
Acute unstable angina (defined during current hospital stay).
Suspicion of acute myocardial infarction.
Considered to have a left ventricular ejection fraction of less than 30%. Decision to exclude is predicated on the Investigator's opinion, and may be based on any combination of acute presentations, recently performed diagnostic studies, or a history that suggests poor cardiac function. Pulmonary congestion of a non-cardiac origin or mild congestive failure primarily attributable to etiologies other than poor ventricular function are not exclusion criteria.
Heart rate <50 bpm prior to infusion start.
Systolic blood pressure <90 mmHg prior to infusion start.
Conduction abnormalities except 1st degree AV block and rate-controlled atrial fibrillation; subjects with functional pacemaker capacity may be enrolled.
Subject is hospitalized primarily due to trauma and/or burns, has received general anaesthesia within the 24 hours prior to the start of study drug infusion, or is anticipated to require general anaesthesia within 24 hours after the start of the infusion.
Subject has participated in a trial with any experimental drug within 30 days prior to enrollment in the study, or has ever been enrolled in this study.
Subject is unable to undergo any procedure required by the protocol.
Subject has laboratory results indicating the presence of liver disease consistent with a Child-Pugh score >9 (Grade C).
Subject has acute hepatitis, history or presence of chronic hepatitis, and/or has had a positive result for Hepatitis B Surface Antigen Test.
Subject requires dialysis (eg, hemodialysis, peritoneal dialysis, Continuous Venovenous Hemodialysis [CVVHD]).
Subject has a known, uncontrolled seizure disorder.
Subject has, per the Investigator's judgment, a known or suspected physical or psychological dependence on an abused drug, other than alcohol.
Subject has a known psychiatric illness that could confound a normal response to sedative treatment.
Subject is incarcerated.
Subject is terminally ill with a life duration expectancy of ≤60 days.
Subject has any other condition or factor which, in the Investigator's opinion, might increase the risk to the subject.

Trial locations and contacts

96 sites in 5 countries.

Country

City, postcode or hospital

96 sites in 5 countries

United States78 sites

Study site
Akron, Ohio, 44307
Study site
Alexandria, Louisiana, 71301
Study site
Arlington Heights, Illinois, 60005
Study site
Atlanta, Georgia
Study site
Augusta, Georgia, 30909
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Baltimore, Maryland, 21201
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Bay Pines, Florida, 33744
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Biddeford, Maine, 04005
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Birmingham, Alabama, 35294
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Boston, Massachusetts, 02115
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Brooklyn, New York, 11215
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Buffalo, New York, 14215
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Camden, New Jersey, 08103
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Chandler, Arizona, 85248
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Chapel Hill, North Carolina, 27599
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Charleston, South Carolina, 29425
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Charlotte, North Carolina, 28207
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Dallas, Texas
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Danville, Pennsylvania, 17882
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Davis, California, 95616
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Dayton, Ohio, 45429
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Denver, Colorado, 80204
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Englewood, New Jersey, 07631
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Farmington, Connecticut, 06030
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Flint, Michigan, 48532
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Galveston, Texas, 77555
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Gordon, Georgia, 30905
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Greensboro, North Carolina
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Hazard, Kentucky, 41701
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Houston, Texas, 77024
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Indianapolis, Indiana
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Iowa City, Iowa, 52242
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Kansas City, Kansas, 66160
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Kettering, Ohio, 45429
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Loma Linda, California, 92354
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Louisville, Kentucky
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Lubbock, Texas, 79430
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Lynchburg, Virginia, 24501
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Madison, Wisconsin, 53792
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Medford, Oregon, 97504
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Memphis, Tennessee, 38163
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Miami, Florida
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Mineola, New York, 11501
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Missoula, Montana
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Monroeville, Pennsylvania, 15146
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Morgantown, West Virginia, 26505
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New Haven, Connecticut, 06520
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New York, New York, 10011
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Newark, Delaware, 19718
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Oak Park, Illinois, 60302
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Ogden, Utah, 84403
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Olathe, Kansas, 66061
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Olkahoma City, Oklahoma, 73104
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Omaha, Nebraska, 68131
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Orlando, Florida, 32804
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Palo Alto, California, 94304
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Pasadena, California, 91105
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Peoria, Illinois, 61603
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Phoenix, Arizona
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Pittsburgh, Pennsylvania, 15219
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Portland, Maine
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Redlands, California, 92373
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Rochester, New York, 14642
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Rogers, Arkansas, 72756
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Sacramento, California, 95819
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San Clemente, California, 92672
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San Francisco, California
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San Jose, California
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Scottsdale, Arizona, 85258
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Shreveport, Louisiana
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Spartanburg, South Carolina, 29303
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Stoney Brook, New York, 11794
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Syracuse, New York, 13210
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Tampa, Florida, 33606
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The Bronx, New York
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Toledo, Ohio
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Washington D.C., District of Columbia, 20010
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Winston-Salem, North Carolina

Other trials in United States

Australia8 sites

Study site
Blacktown, New South Wales, 2148
Study site
Box Hill, Victoria, 3128
Study site
Heidelberg, Victoria, 3084
Study site
Hobart, Tasmania, 7001
Study site
Parkville, Victoria, 3050
Study site
Perth, Western Australia, 6000
Study site
Randwick, New South Wales, 2031
Study site
Woodville, South Australia, 5011

Other trials in Australia

Brazil5 sites

Study site
Pedro de Toledo, São Paulo, 04039-901
Study site
Porto Alegre, Rio Grande do Sul, 90020-090
Study site
Porto Alegre, Rio Grande do Sul, 90610-000
Study site
Santo André, São Paulo, 09190-610
Study site
São Paulo, São Paulo, 01323-001

Other trials in Brazil

New Zealand4 sites

Study site
Christchurch, 8001
Study site
Hastings, 4201
Study site
Palmerston North, 5301
Study site
Welling, 6002

Other trials in New Zealand

Argentina1 site

Study site
Ciudad de Buenos Aires

Other trials in Argentina

About this study

Official title: A Phase 4, Randomized, Double-Blind, Multi-Center, Comparator Study Evaluating the Safety and Efficacy of Dexmedetomidine Compared to IV Midazolam in ICU Subjects Requiring Greater Than Twenty-Four Hours of Continuous Sedation

The purpose of this study is to evaluate the safety and efficacy of dexmedetomidine in ICU subjects who are initially intubated, mechanically ventilated and require sedation for beyond 24 hours.

Read the detailed description

Traditional agents such benzodiazepines and propofol have long been used to sedate critically ill patients. Unfortunately, these agents have serious disadvantages that may have a negative impact on patient outcomes. These disadvantages include respiratory depression, prolonged mechanical ventilation, paradoxical agitation, myocardial depression, hypotension, tachyphylaxis, physical dependence, and an unpredictable duration of action following long term infusions. Additionally, concomitant use of an opioid or other analgesic is often required for ICU patients to achieve adequate levels of pain relief, which may also prolong awakening and possibly increase respiratory depression.

Dexmedetomidine may offer a new treatment option that remedies many of the deficiencies of traditional sedatives. This agent would provide for accurate, titratable sedation and analgesia without the concurrent respiratory depression and accumulation common to other agents. It may permit greater patient interaction due to reduced impairment of cognition and may reduce risks associated with opioids due to its analgesia sparing property. Although such a drug may have important benefits for ICU patients requiring sedation for greater than 24 hours, dexmedetomidine is not currently approved for such long-term usage.

Conditions: Mechanically Ventilated and Intubated Subjects
Being tested: Dexmedetomidine HCL Injection, Midazolam Injection
Keywords: Sedation, ICU, Anesthesia, Dexmedetomidine, Midazolam

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dexmedetomidine HCL InjectionDrug
Midazolam InjectionDrug

Study groups in NCT00216190
Study group	Role	What they receive
Dexmedetomidine	Experimental	Not described Receives: Drug: Dexmedetomidine HCL Injection
Midazolam	Active comparator	Not described Receives: Drug: Midazolam Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

The percentage of time spent within the protocol specified sedation range (Richmond Agitation-Sedation Scale [RASS] range of -2 to +1)
RASS Range:
Score +1 (Restless: Anxious; but movements not aggressive or vigorous) Score 0 (Alert and calm) Score -1 (Drowsy: Not fully alert, but has sustained awakening [eye opening/eye contact] to voice [≥10 seconds]) Score -2 (Light sedation: Briefly awakens with eye contact to voice [< 10 seconds])
Measured: Preinfusion, Treatment period: every 10min for 30min, 1 & 4 hr after infusion starts, every 4 hrs, prior to end of infusion & extubation. Follow-up Period (48hrs): every 10min for 1st 30min after drug discontinuation, 1, 4, 8,12, 24 & 48 hr post infusion

Secondary outcomes (9)

Percentage of subjects able to achieve a RASS between - 2 and +1 without interruption of study drug
Measured: Preinfusion, Treatment period: every 10min for 30min, 1 & 4 hr after infusion starts, every 4 hrs, prior to end of infusion & extubation. Follow-up Period (48hrs): every 10min for 1st 30min after drug discontinuation, 1, 4, 8,12, 24 & 48 hr post infusion
Percentage of subjects with evidence of delirium (Confusion Assessment Method [CAM]-ICU positive) while on study drug
Measured: Prior to the start of the study drug infusion. Daily each morning beginning the day after starting study drug, and at the end of study drug infusion.
Percentage of subjects with evidence of delirium (CAM-ICU positive) following discontinuation of study drug
Measured: At 12, 24, 36, and 48 hrs after end of infusion. Every 12 hours during the 48-hour Follow-Up Period.
Time to achieving a RASS between -2 and +1 for daily arousal assessment
Measured: Prior to the start of the study drug infusion. Daily each morning beginning the day after starting study drug, and at the end of study drug infusion.
Percentage of subjects who can interact with caregivers
Percentage of subjects who can interact with caregivers (i.e., follow at least 3 of the 4 arousal assessment commands) while in the protocol-specified RASS range of -2 to +1
Measured: Prior to start of infusion (Day 0), daily each morning throughout the Treatment Period beginning on the day after randomization (Study Day 1), and immediately prior to discontinuation of study drug infusion at the end of Treatment Period.
Overall drug (sedative) tolerance
Measured: During the treatment period (Approximately 30 days)
Fentanyl use
Measured: During the treatment period (Approximately 30 days)
Nursing assessment
Measured: Screening period, during the treatment period (Approximately 30 days), and 48-hours of follow-up period
Use of rescue midazolam for sedation
Measured: During the treatment period (Approximately 30 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2005Aug 2007

First posted22 Sep 2005 (estimated)
Study startMar 2005
Study completionAug 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Mechanically Ventilated and Intubated SubjectsStudies 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: Parallel groups
Masking: Double blind
Enrolment: 420 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00216190
Sponsor's protocol ID: 2001-001
Status last verified: Jul 2015
First submitted: 31 Aug 2005
Last updated: 23 Jul 2015
Results posted: No
Data monitoring committee: No

Publications

Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.
PubMed 19188334

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 4, Randomized, Double-Blind, Multi-Center, Comparator Study Evaluating the Safety and Efficacy of Dexmedetomidine Compared to IV Midazolam in ICU Subjects Requiring Greater Than Twenty-Four Hours of Continuous Sedation
ClinicalTrials.gov ID: NCT00216190
Acronym / sponsor ID: 2001-001
Conditions: Mechanically Ventilated and Intubated Subjects
Keywords: Sedation, ICU, Anesthesia, Dexmedetomidine, Midazolam
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 420 participants (actual)
Lead sponsor: Hospira, now a wholly owned subsidiary of PfizerIndustry (pharma, biotech, devices)
Study start: Mar 2005
Study completion: Aug 2007 (actual)
First posted: 22 Sep 2005 (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 purpose of this study is to evaluate the safety and efficacy of dexmedetomidine in ICU subjects who are initially intubated, mechanically ventilated and require sedation for beyond 24 hours.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 2

Arm	Type	Receives
Dexmedetomidine	Experimental	Drug: Dexmedetomidine HCL Injection
Midazolam	Active comparator	Drug: Midazolam Injection

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Subject is ≥18 years of age.
If female, subject is non-lactating, and is either:
Subject is initially intubated and mechanically ventilated, or is planned for imminent intubation and mechanical ventilation, sedation is anticipated to be required during mechanical ventilation, and mechanical ventilation is anticipated to continue for at least 72 hours.
Subject or subject's legally authorized representative has voluntarily signed and dated an informed consent form, approved by the applicable Institutional Review Board (IRB), after the nature of the study has been explained and the subject or subject's legally authorized representative has had the opportunity to ask questions. The informed consent must be signed before any study specific procedures are performed.
Subject is sedated within a Richmond Agitation-Sedation Scale (RASS) range of -2 to +1 at the time of initiation of study drug

Key exclusion criteria (25 listed)

Subject has been intubated for greater than 96 hours prior to the initiation of study drug (thus, the attainment of consent, screening evaluations, and randomization must all have been completed by the 96th hour post-intubation, so that the actual initiation of the study drug infusion may start by the end of the 96 hour window).
Subject has serious central nervous system pathology/trauma that, per clinical judgment of the Investigator, precludes responsiveness or survival.
Subject for whom opiates, benzodiazepines, or dexmedetomidine are contraindicated, or who has known or suspected serious allergy to any drug that might be administered during the course of the study.
Subject for whom alpha-2 agonists are contraindicated.
Subject requires neuromuscular blocking agents during the study for use other than intubation.

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
Dexmedetomidine HCL Injection	Drug	Dexmedetomidine
Midazolam Injection	Drug	Midazolam

Primary outcome

The percentage of time spent within the protocol specified sedation range (Richmond Agitation-Sedation Scale [RASS] range of -2 to +1)
Time frame: Preinfusion, Treatment period: every 10min for 30min, 1 & 4 hr after infusion starts, every 4 hrs, prior to end of infusion & extubation. Follow-up Period (48hrs): every 10min for 1st 30min after drug discontinuation, 1, 4, 8,12, 24 & 48 hr post infusion
RASS Range: Score +1 (Restless: Anxious; but movements not aggressive or vigorous) Score 0 (Alert and calm) Score -1 (Drowsy: Not fully alert, but has sustained awakening [eye opening/eye contact] to voice [≥10 seconds]) Score -2 (Light sedation: Briefly awakens with eye contact to voice [< 10 seconds])

9 secondary outcomes

Percentage of subjects able to achieve a RASS between - 2 and +1 without interruption of study drug
Time frame: Preinfusion, Treatment period: every 10min for 30min, 1 & 4 hr after infusion starts, every 4 hrs, prior to end of infusion & extubation. Follow-up Period (48hrs): every 10min for 1st 30min after drug discontinuation, 1, 4, 8,12, 24 & 48 hr post infusion
Percentage of subjects with evidence of delirium (Confusion Assessment Method [CAM]-ICU positive) while on study drug
Time frame: Prior to the start of the study drug infusion. Daily each morning beginning the day after starting study drug, and at the end of study drug infusion.
Percentage of subjects with evidence of delirium (CAM-ICU positive) following discontinuation of study drug
Time frame: At 12, 24, 36, and 48 hrs after end of infusion. Every 12 hours during the 48-hour Follow-Up Period.
Time to achieving a RASS between -2 and +1 for daily arousal assessment
Time frame: Prior to the start of the study drug infusion. Daily each morning beginning the day after starting study drug, and at the end of study drug infusion.
Percentage of subjects who can interact with caregivers
Time frame: Prior to start of infusion (Day 0), daily each morning throughout the Treatment Period beginning on the day after randomization (Study Day 1), and immediately prior to discontinuation of study drug infusion at the end of Treatment Period.
Overall drug (sedative) tolerance
Time frame: During the treatment period (Approximately 30 days)
Fentanyl use
Time frame: During the treatment period (Approximately 30 days)
Nursing assessment
Time frame: Screening period, during the treatment period (Approximately 30 days), and 48-hours of follow-up period
Use of rescue midazolam for sedation
Time frame: During the treatment period (Approximately 30 days)

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 23 Jul 2015.
Derived from this study: PubMed 19188334Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2.

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.

The record lists no contact. Use the official record to reach the sponsor.

96 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 25 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 23 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 96 sites in United States, Australia, Brazil, New Zealand, Argentina. 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?

The percentage of time spent within the protocol specified sedation range (Richmond Agitation-Sedation Scale [RASS] range of -2 to +1) (time frame: Preinfusion, Treatment period: every 10min for 30min, 1 & 4 hr after infusion starts, every 4 hrs, prior to end of infusion & extubation. Follow-up Period (48hrs): every 10min for 1st 30min after drug discontinuation, 1, 4, 8,12, 24 & 48 hr post infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00216190, which also lists 1 linked publication.

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 23 Jul 2015.