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

NCT02773797 | Withdrawn Phase 4 DMC

• 1 other identifier: Nystrom02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

COPD

Keywords

Sedation; Dexmedetomidine

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (3)

IN-DEX 1.0 mcg/kg, intranasal saline

PLACEBO COMPARATOR

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

IN-DEX, 1.5 mcg/kg intranasal saline

PLACEBO COMPARATOR

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

Placebo - Saline

ACTIVE COMPARATOR

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

Interventions

IN-DEX 1.0 mcg/kg, intranasal saline DRUG

Also known as: precedex

IN-DEX 1.0 mcg/kg, intranasal saline

IN-DEX 1.5 mcg/kg, intranasal saline DRUG

Also known as: precedex

IN-DEX, 1.5 mcg/kg intranasal saline

Placebo - Saline DRUG

Placebo - Saline

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Dayton VA Medical Center: lead

Study Sites (1)

Dayton VA Medical Center

Dayton, Ohio, 45428, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2016
• First Posted: May 16, 2016
• Study Start: August 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: April 1, 2018
• Last Updated: July 31, 2018

Record last verified: 2018-07

Locations

US (1)