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

• ClinicalTrials.gov Identifier: NCT02773797
• Recruitment Status: Withdrawn
• First Posted: May 16, 2016
• Last Update Posted: July 31, 2018
• Sponsor: Dayton VA Medical Center
• Information provided by (Responsible Party): Dayton VA Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COPD	Drug: IN-DEX 1.0 mcg/kg, intranasal saline; Drug: IN-DEX 1.5 mcg/kg, intranasal saline; Drug: Placebo - Saline	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Sedation and Physiologic Response to Intranasal Dexmedetomidine in Severe Chronic Obstructive Pulmonary Disease (COPD): A Randomized, Blinded, Placebo Controlled Crossover Trial
• Study Start Date: August 2016
• Estimated Primary Completion Date: July 2017
• Estimated Study Completion Date: April 2018

Arms and Interventions

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 Name: 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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Modified Observer's Assessment of Alertness/Sedation Scale [ Time Frame: every 15 minutes up to 5 hours after intranasal dexmedetomidine ]
2. Sedation Visual Analog Scale (VAS) [ Time Frame: Every 15 minutes up to 5 hours after intranasal dexmedetomidine ]
3. Changes in Vital Signs [ Time Frame: Every 5 minutes for 90 minutes, then every 15 minutes for up to 5 hours ]
   heart rate, noninvasive blood pressure, respiratory rate, continuous pulse oximetry

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Ohio

Dayton VA Medical Center

Dayton, Ohio, United States, 45428

Sponsors and Collaborators

Dayton VA Medical Center

More Information

• Responsible Party: Dayton VA Medical Center
• ClinicalTrials.gov Identifier: NCT02773797
• Other Study ID Numbers: Nystrom02
• First Posted: May 16, 2016
• Last Update Posted: July 31, 2018
• Last Verified: July 2018

Keywords provided by Dayton VA Medical Center:

Sedation; Dexmedetomidine

Additional relevant MeSH terms:

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