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

Acute Respiratory Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00871624
• Other study ID #: TuftsMedicalCenter 8533
• Status: Completed
• Phase: Phase 2
• First received: March 27, 2009
• Last updated: November 20, 2017
• Start date: March 2009
• Est. completion date: February 2013

Study information

• Verified date: November 2017
• Source: Tufts Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Respiratory Failure
• Respiratory Distress Syndrome, Adult
• Respiratory Insufficiency

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts
United States	Winchester Hospital	Winchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Tufts Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerability of NIV as Assessed by an NIV Tolerance Score	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)	Completed at time 0min, 30min, 60min, 3hr, 6hr, 12hr, and then every 12 hours after the start of NPPV therapy up to 72 hours
Secondary	Percent of Study Time Spent With a Riker-SAS Score Between 3 and 4 Inclusive	Percentage of time spent at desired sedation goal	Completed at baseline and every 4 hours after the start of NPPV therapy for the duration of the study