Dexmedetomidine for Postoperative Sedation in Patients Undergoing Repair of Thoracoabdominal Aortic Aneurysms

This study has been terminated.
(Surgical approach changed therefore subject enrollment not possible.)
Sponsor:
Collaborator:
Hospira, Inc.
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00409344
First received: December 7, 2006
Last updated: September 16, 2009
Last verified: September 2009

December 7, 2006
September 16, 2009
January 2007
January 2008   (final data collection date for primary outcome measure)
  • Time to a Successful Spontaneous Breathing Trial. [ Time Frame: 1/1/2008 ] [ Designated as safety issue: No ]
  • Intensive Care Unit Length of Stay [ Time Frame: 1/1/2008 ] [ Designated as safety issue: No ]
Primary outcomes: Time to a successful spontaneous breathing trial, ICU length of stay
Complete list of historical versions of study NCT00409344 on ClinicalTrials.gov Archive Site
  • Secondary Endpoints Include:Amount of Sedative and Opiates Given [ Time Frame: 1/1/2008 ] [ Designated as safety issue: No ]
  • Time to Extubation [ Time Frame: 1/1/2008 ] [ Designated as safety issue: No ]
  • Amount of Vasoactive Substances Used to Achieve Hemodynamic Stability [ Time Frame: 1/1/2008 ] [ Designated as safety issue: No ]
  • Pharmaco-economics [ Time Frame: 1/1/2008 ] [ Designated as safety issue: No ]
  • Incidence of Delirium; Number of Shifts During Which Delirium Was Diagnosed [ Time Frame: 1/1/2008 ] [ Designated as safety issue: Yes ]
  • Secondary endpoints include:
  • Time to extubation
  • Amount of sedative and opiates given
  • Amount of vasoactive substances used to achieve hemodynamic stability
  • Pharmaco-economics
  • Incidence of delirium; number of shifts during which delirium was diagnosed
Not Provided
Not Provided
 
Dexmedetomidine for Postoperative Sedation in Patients Undergoing Repair of Thoracoabdominal Aortic Aneurysms
Phase 4 Study of Dexmedetomidine for Postoperative Sedation in Patients Undergoing Repair of Thoracoabdominal Aortic Aneurysms

The primary objective of this study is to test the hypothesis that time on the ventilator and ICU length of stay will be shorter in TAA patients given postoperative sedation with dexmedetomidine compared to those given standard sedation. Secondary endpoints are: requirement for sedatives vasoactive drugs incidence of postoperative delirium and cost analysis.

Repair of thoraco-abdominal aortic aneurysms (TAA) is mostly performed in specialized centers. These centers report an operative mortality around 10%. In an analysis of 337 consecutive TAA, Cambria et al reported pulmonary (44%), cardiac, (13.8 %) renal (13.5%) and postoperative spinal cord deficit as prominent complications. Due to the extent of the surgery and the high risk of complications, all these patients require post- operative care in the Intensive Care Unit (ICU). In 2003, the operation was performed in approximately 40 patients at the Massachusetts General Hospital (MGH). The median length of stay in the ICU was 7 days (range 2-55) All patients required postoperative mechanical ventilation for greater than 48 h. During this period, a continuous intravenous infusion of propofol is normally used for sedation. Pain relief is provided by a continuous intravenous infusion of hydromorphone. This combination of sedation and analgesia is widely used at MGH and other institutions. Although very effective, it may cause respiratory depression and a deep sedative state, which may result in a prolonged requirement for mechanical ventilation. Lighter or more controllable sedation appears to be beneficial in this regard: daily wake up of intubated and sedated ICU patients decreases days on the ventilator and length of stay in the ICU.

Dexmedetomidine is a highly specific α2 agonist with prominent central nervous system (CNS) and cardiovascular effects It is FDA-approved as a postoperative sedative-hypnotic agent for intensive care patients for use up to 24 hours. The drug has hypnotic, sedative, analgesic and anxiolytic actions, and it tends to cause a mild decrease in blood pressure and heart rate. Patients or healthy volunteers sedated with dexmedetomidine alone are easily arousable and have no apparent respiratory depression. Dexmedetomidine has synergistic hypnotic and analgesic interactions with virtually all CNS depressants tested. It significantly decreases sedative and opioid requirements during and after major surgical procedures.Other potentially beneficial effects that are not as well-documented include bronchodilation and the ability to induce a more 'physiologic' sleep than other hypnotics commonly used in the ICU. Dexmedetomidine sedation may also be associated with a lower incidence of delirium.

Patients recovering from TAA surgery routinely require substantial ICU resources. If dexmedetomidine decreases the opioid and sedative requirement in these patients, it may potentially decrease the average number of days spent on the ventilator and in the ICU.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
  • Sedation
  • Respiration, Artificial
  • Length of Stay
  • Drug: Dexmedetomidine
    A continuous infusion of dexmedetomidine will be started at a dose of 0.8mcg/kg/hr. This will continue for no longer than 24 hours. Four hours post extubation the study drug wii be discontinued using a standard tapering protocol: 0.6mcg/kg/hr for 4 hours then 0.4mcg/kg/hr for 4 hours, then 0.2 mcg/kg/hr for 4 hours and then 0.1mcg/kg/hr for 4 hours and then turned off.
    Other Name: No other names have been specified
  • Other: Normal Saline
    Normal Saline will be given as the placebo and will administered at 0.8mcg/kg/hr
    Other Name: No other names have been specified
  • Placebo Comparator: 1
    Normal Saline
    Intervention: Other: Normal Saline
  • Active Comparator: Dexmedetomidine
    Dexmedetomidine is a highly specific a2 agonist with prominent central nervous system and cardiovascular effects. A postoperative sedative-hypnotic agent for intensive care patients for use up to 24 hours.
    Interventions:
    • Drug: Dexmedetomidine
    • Other: Normal Saline
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
0
January 2008
January 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • All Patients over age 18 undergoing non-emergent repair of type I-III TAA

Exclusion Criteria:

  • Pregnancy
  • Patients with hepatic impairment (increase of ALT or AST three times normal)
  • Patient taking clonidine or tricyclic antidepressants.
  • Patients taking opioids or benzodiazepines chronically (> 2 doses a day for > 1 month)
  • Patients with second or third degree heart block without a pacer
  • Patients undergoing emergency repair of TAA
  • Intraoperative cardiac arrest
  • Intraoperative massive blood loss (>10 l)
Both
18 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00409344
2006-P-001827, IND:74068
Yes
Ulrich Schmidt, MD PhD, Massachusetts General Hospital
Massachusetts General Hospital
Hospira, Inc.
Principal Investigator: Ulrich Schmidt, MD,PhD Massachusetts General Hospital
Massachusetts General Hospital
September 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP