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

Study Overview
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Brief Summary
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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.

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

Conditions
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COPD

Intervention / Treatment
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* Drug: IN-DEX 1.0 mcg/kg, intranasal saline
* Drug: IN-DEX 1.5 mcg/kg, intranasal saline
* Drug: Placebo - Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: IN-DEX 1.0 mcg/kg, intranasal saline<br>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<br> <br> * Other names: precedex;|
| Placebo Comparator: IN-DEX, 1.5 mcg/kg intranasal saline<br>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<br> <br> * Other names: precedex;|
| Active Comparator: Placebo - Saline<br>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<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sedation, Dexmedetomidine