Placebo Controlled Evaluation of Sedation and Physiological Response to Intranasal Dexmedetomidine in Severe COPD

Sedation and Physiologic Response to Intranasal Dexmedetomidine in Severe Chronic Obstructive Pulmonary Disease (COPD): A Randomized, Blinded, Placebo Controlled Crossover Trial

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 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 (IN-DEX) to induce light to moderate sedation of several hours duration.

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

The study is an extension of a similarly designed pilot study which did not include a placebo comparison. Results of the study will be helpful to design additional trials with intranasal dexmedetomidine in acutely symptomatic COPD patients, exertional dyspnea and exercise performance, and dyspnea treatment comparisons.

Study Overview

• Status: Withdrawn
• Conditions: COPD
• Intervention / Treatment: Drug: IN-DEX 1.0 mcg/kg, intranasal saline; Drug: IN-DEX 1.5 mcg/kg, intranasal saline; Drug: Placebo - Saline

• Study Type: Interventional
• 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 < 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)

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 > 2x 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: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: IN-DEX 1.0 mcg/kg, intranasal saline; Patients with clinically stable severe COPD will be randomized. Each group will participate in 3 drug study sessions separated by 7-14 days. Arm label "Intranasal-Dexmedetomidine (IN-DEX) intranasal 1.0 mcg/kg" will participate in 3 drug study sessions separated by 7-14 days. All drug study sessions will be conducted in a monitored acute care setting with medical staff in attendance. Sedation assessment and vital signs will be recorded at 15 minute and 5-15 minute intervals respectively, for a minimum of 3 hours.	Drug: IN-DEX 1.0 mcg/kg, intranasal saline; Other Names: precedex
Placebo Comparator: IN-DEX, 1.5 mcg/kg intranasal saline; Patients with clinically stable severe COPD will be randomized. Each group will participate in 3 drug study sessions separated by 7-14 days. Arm label "IN-DEX intranasal 1.5 mcg/kg" will participate in 3 drug study sessions separated by 7-14 days. All drug study sessions will be conducted in a monitored acute care setting with medical staff in attendance. Sedation assessment and vital signs will be recorded at 15 minute and 5-15 minute intervals respectively, for a minimum of 3 hours.	Drug: IN-DEX 1.5 mcg/kg, intranasal saline; Other Names: precedex
Active Comparator: Placebo - Saline; Patients with clinically stable severe COPD will be randomized. Each group will participate in 3 drug study sessions separated by 7-14 days. Arm label "Placebo - Saline" will participate in 3 drug study sessions separated by 7-14 days. All drug study sessions will be conducted in a monitored acute care setting with medical staff in attendance. Sedation assessment and vital signs will be recorded at 15 minute and 5-15 minute intervals respectively, for a minimum of 3 hours.	Drug: Placebo - Saline

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 dexmedetomidine
Sedation Visual Analog Scale (VAS)		Every 15 minutes up to 5 hours after intranasal dexmedetomidine
Changes in Vital Signs	heart rate, noninvasive blood pressure, respiratory rate, continuous 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: August 1, 2016
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 13, 2016
• First Posted (Estimate): May 16, 2016

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 30, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Sedation; Dexmedetomidine
• 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: Nystrom02