Efficacy and Safety of Dexmedetomidine During Non-Invasive Positive Pressure Ventilation

Study Description

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Brief Summary:

The purpose of the study is to determine the efficacy and safety of dexmedetomidine during Non-invasive positive pressure ventilation (NPPV) for patients with acute respiratory failure compared to standard analgesic/sedation practices

Condition or disease	Intervention/treatment	Phase
Acute Respiratory Failure	Drug: Dexmedetomidine; Drug: Placebo	Phase 2

Detailed Description:

Non-invasive positive-pressure ventilation (NPPV) is increasingly being used to manage patients with acute respiratory failure (ARF) in an effort to avoid the numerous negative sequelae associated with intubation and mechanical ventilation. In the USA, it is estimated that 20-30% of all patients placed on mechanical ventilation are treated with NPPV. Indications for NPPV include but are not limited to acute or acute-on-chronic hypercapnic respiratory failure, pulmonary edema, respiratory failure in immunocompromised patients or that due to chest wall deformity or neuromuscular disease. For NPPV to be successful, it is critical that the patient be cooperative and comfortable (i.e. no pain) as agitation and discomfort interfere with the success of NPPV.

Despite the importance of patient comfort during NPPV, physicians infrequently use sedation or analgesic therapy during NPPV, primarily due to concerns about the respiratory depressant effects of most of the sedatives (e.g., benzodiazepines) and analgesics (e.g., opioids) that are currently available. In addition, neither the benzodiazepines nor opioids are easily titratable, can easily accumulate and can be associated with both the development of delirium and a withdrawal effect.

Dexmedetomidine is an intravenous rapid-onset, short acting ά 2-receptor agonist that is approved for short-term sedation in post-operative and critically ill patients. It has been stated that this drug produces a state of "cooperative sedation" allowing the patient to interact with health care providers. Dexmedetomidine has been used for its ability to cause sympatholysis and, because of analgesic properties, to decrease the need for opioids. Potential advantages include its short half life and intravenous route of administration, permitting rapid titration to achieve sedation targets and, in patients with respiratory failure; it can provide both sedation and analgesia without inducing respiratory depression. Despite these advantages, it is currently used by less than 5% of pulmonologists/ intensivists as the primary sedative option during NPPV and has not been studied in a controlled fashion in this population. Therefore, dexmedetomidine may prove to be more efficacious and safe compared to standard sedation/analgesic therapy during NPPV.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	36 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Efficacy and Safety of Dexmedetomidine During Non-Invasive Positive Pressure Ventilation for Patients With Acute Respiratory Failure: A Randomized, Double-blind, Placebo-controlled Pilot Study
Study Start Date :	March 2009
Actual Primary Completion Date :	February 2013
Actual Study Completion Date :	February 2013

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Dexmedetomidine; Subjects received active dexmedetomidine 0.2 -0.7 mcg/kg/hr	Drug: Dexmedetomidine; Dexmedetomidine will be started at a rate of 0.2mcg/kg/hr and titrated by 0.1 mcg/kg/hr every 30 minutes to a maximum of 0.7 mcg/kg/hr to maintain a Riker-SAS 3-4.; Other Name: Precedex
Placebo Comparator: Placebo; Subjects received placebo saline solution 0.2-0.7 mcg/kg/hr	Drug: Placebo; Placebo infusion will be started at a rate of 0.2mcg/kg/hr and titrated by 0.1 mcg/kg/hr every 30 minutes to a maximum of 0.7 mcg/kg/hr to maintain a Riker-SAS 3-4.; Other Name: Precedex

Outcome Measures

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Primary Outcome Measures :

1. Tolerability of NIV as Assessed by an NIV Tolerance Score [ Time Frame: Completed at time 0min, 30min, 60min, 3hr, 6hr, 12hr, and then every 12 hours after the start of NPPV therapy up to 72 hours ]
   NIV tolerance (NIV intolerance score =1 out of 4) A score of 1 for a comfortable and relaxed patient tolerating NIV; a score of 2 for mild intolerance with some discomfort and occasionally grabbing at the NIV mask; a score of 3 for moderate intolerance and discomfort with the NIV mask most of the time but more frequent grabbing at the mask, sometimes pulling it off; and a score of 4 for severe NIV intolerance with agitation and the inability to leave the NIV mask in place. The outcome measure description of the time frame is reported as the average of the NIV tolerance scores reported at the various time frames (0min, 30min, 60 min, 3hr, 6hr, 12hr, and then every 12hr after the start of NIV therapy up to 72 hours)

Secondary Outcome Measures :

1. Percent of Study Time Spent With a Riker-SAS Score Between 3 and 4 Inclusive [ Time Frame: Completed at baseline and every 4 hours after the start of NPPV therapy for the duration of the study ]
   Percentage of time spent at desired sedation goal

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Age ≥ 18 years
• Acute respiratory failure requiring the initiation of NPPV
• Admission to the medical ICU service at Tufts Medical Center or Winchester Hospital

Exclusion Criteria:

• Patients with delirium (intensive care delirium screening checklist score ≥ 4) or disorientation (not oriented to person or place)
• Receiving NPPV for ≥ 8 hours (includes treatment with NPPV at an outside hospital)
• Intubation and mechanical ventilation in the past month based on hospital admission note
• Age ≥ 85 years
• Inability of the potential subject to give informed consent
• Current treatment with antipsychotic agent based on hospital admission note
• Heart rate ≤ 50 bpm
• Systolic blood pressure ≤ 90 mmHg
• History of heart block without pacemaker use or severe ventricular dysfunction (EF ≤25%) based on hospital admission note
• Acute alcohol withdrawal based on hospital admission note
• History of end stage liver failure (based on presence of ≥ 1 or more of the following: AST/ALT ≥ 2 times ULN, INR ≥ 2, total bilirubin ≥ 1.5
• Irreversible brain disease consistent with severe dementia based on hospital admission note
• Pregnancy (all women of child-bearing age will undergo a pregnancy test prior to study enrollment)
• Treatment with clonidine or dexmedetomidine in the past 30 days based on hospital admission note
• Known allergy or sensitivity to clonidine or dexmedetomidine

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Winchester Hospital
Winchester, Massachusetts, United States, 01890

Sponsors and Collaborators

Tufts Medical Center

Investigators

Principal Investigator:	Nicholas S Hill, MD	Tufts Medical Center / Winchester Hospital

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Tufts Medical Center
ClinicalTrials.gov Identifier:	NCT00871624 History of Changes
Other Study ID Numbers:	TuftsMedicalCenter 8533
First Posted:	March 30, 2009
Results First Posted:	December 7, 2015
Last Update Posted:	December 18, 2017
Last Verified:	November 2017

Additional relevant MeSH terms:

Respiratory Insufficiency; Respiratory Distress Syndrome, Adult; Respiration Disorders; Respiratory Tract Diseases; Lung Diseases; Dexmedetomidine; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic	Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action