Sedation and Physiological Effects of Intranasal Dexmedetomidine in Severe COPD

A variety of medications have been used to treat the anxiety, discomfort, and fear associated with continuous and sudden episodic breathlessness in patients with advanced respiratory disease. Opioids and benzodiazepines, used alone or in combination, are commonly prescribed for this distressing symptom. Clinicians are concerned about the adverse effects of opioids, especially respiratory depression, so they frequently prescribe benzodiazepines. Recent studies have shown that benzodiazepine use is associated with increased adverse respiratory outcomes in older adults with Chronic Obstructive Pulmonary Disease (COPD).

Dexmedetomidine may be an alternative to current drug therapies for breathlessness. Dexmedetomidine produces a dose dependent sedation, anxiolysis, and analgesia without respiratory depression or cognitive dysfunction. The drug can be administered intranasally to induce light to moderate sedation of several hours duration.

The objective of the proposed research, a pilot study, is to assess the dose dependent safety and efficacy of intranasal dexmedetomidine in clinically stable patients with severe COPD. This will be accomplished in a staffed acute care setting with routine vital signs monitoring and pulse oximetry. Patients will be assessed objectively and subjectively for their level of sedation by validated sedation scales.

This pilot study is an initial investigation of a drug with favorable pharmacologic properties in this patient population with distressing and difficult to treat symptoms. The pilot study may provide evidence that a larger trial is needed to confirm the study results, or evidence that additional study in symptomatic patients and treatment comparison trials should be pursued.

Study Overview

• Status: Completed
• Conditions: Sedation; Dexmedetomidine; COPD
• Intervention / Treatment: Drug: Intranasal dexemdetomidine (IN-DEX)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Dayton, Ohio, United States, 45428
      • Dayton VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Severe COPD (FEV1 30-50% predicted)
• Age 45-70
• American Society of Anesthesiologists (ASA) Class 3
• Body Mass Index <35 kg/meter squared
• No prior history of adverse reactions to alpha 2 agonists (dexmedetomidine, clonidine)
• Women of non-child bearing age

Exclusion Criteria:

• known adverse reaction, allergy or hypersensitivity, to alpha 2 agonists
• not nothing by mouth (NPO)
• ASA class >3
• Home oxygen therapy >2LPM by nasal cannula continuous use
• Any evidence of nasal mucosal inflammation, irritation, bleeding or ulceration
• Pregnancy, or possibility of pregnancy
• Coronary heart disease with stable or unstable angina
• Baseline heart rate <55 beats per minute
• Bradyarrhythmia, heart block, presence of pacemaker
• Congestive Heart Failure or known Cardiomyopathy (Ejection Fraction <40% by ECHO, MUGA, or myocardial perfusion imaging)
• Cor pulmonale
• Liver disease (hepatic transaminases above the upper limit of normal, cirrhosis, end stage liver disease)
• diagnosis of moderate to severe Obstructive Sleep Apnea
• currently enrolled in any other research study involving drugs or devices

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IN-DEX; Subjects will be administered 1 mcg/kg or 1.5 mcg/kg intranasal dexemdetomidine (IN-DEX) and monitored for up to 5 hours.	Drug: Intranasal dexemdetomidine (IN-DEX); Other Names: precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Observer's Assessment of Alertness/Sedation Scale		every 15 minutes up to 5 hours after intranasal desmedetomidine
Sedation Visual Analog Scale (VAS)		Every 15 minutes up to 5 hours after intranasal dexemdetomidine
Changes in Vital Signs	Heart rate, noninvasive blood pressure, respitory rate, pulse oximetry	Every 5 minutes for 90 minutes, then every 15 minutes for up to 5 hours

Collaborators and Investigators

• Sponsor: Dayton VA Medical Center

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: August 4, 2014
• First Submitted That Met QC Criteria: August 5, 2014
• First Posted (Estimate): August 7, 2014

Study Record Updates

• Last Update Posted (Actual): July 18, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: Nystrom01