Effect of Zopiclone on Compliance With Continuous Positive Airway Pressure in Obstructive Sleep Apnea

A Double-blind, Randomized, Parallel Group Study to Determine the Effect of Initial Prescription of Zopiclone on the Level of Compliance With CPAP in Adult Patients Treated for OSA at 26 Weeks

The clinical population targeted will be newly diagnosed patients with polysomnographically diagnosed OSA who are not currently taking hypnotics for concomitantly diagnosed insomnia. Outpatients who are also judged to be capable to follow the study procedures (consent, timelines, visits, questionnaires) and who do not have any concurrent disease that in the view of the investigator will interfere with participation in the trial to completion will be included. Approximately 160 subjects were recruited (80 per treatment arm) in the recent trial of eszopiclone. This size is expected to be able to discern an important difference of 80 minutes per night. In the current clinical population newly prescribed CPAP at Mount Sinai Hospital, the average compliance after 4 weeks of initiation of nCPAP was 4:01 (SD 2:59) hours per night. To be able to discern a difference of at least 1 hour (60 minutes) in usage per night, including entirely non-adherent patients who do not use treatment at all as 'zero hour' users, would require randomization of 264 patients (132 per group).

Our hypothesis for this study is that initial titration of CPAP treatment of OSA may be improved by initial prescription of a common hypnotic, zopiclone. To answer this question we intend to recruit 264 consecutive consenting subjects with OSA confirmed by a physician (ABSM or by a respirologist with extensive sleep medicine experience) with supportive polysomnography results who are willing to initiate long-term CPAP treatment.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Placebo; Drug: Zopiclone

Detailed Description

Background: Obstructive sleep apnea (OSA) is a common sleep breathing disorder that is associated with serious complications. Continuous positive airway pressure (CPAP) is the treatment of choice for most patients but its use in the real world is limited by low patient adherence which may result in sub-optimal outcomes for some patients. A single hypnotic with low risk of adverse effects is a cost-effective intervention to augment the currently low adherence to CPAP, especially if only prescribed for a limited time. The hypnotic is generic zopiclone 3.75-7.5 mg at bedtime for up to 14 doses.

The clinical population targeted will be newly expert physician-diagnosed patients polysomnographically supported OSA who are not currently taking hypnotics for concomitantly diagnosed insomnia. Outpatients who are also judged to be capable to follow the study procedures (consent, timelines, visits, questionnaires) and who do not have any concurrent disease that in the view of the investigator will interfere with participation in the trial to completion will be included.

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Cite de la Sante
    • Laval, Quebec, Canada, H7S 2M5
      • Institut de medecine specialisee de Laval
    • Montreal, Quebec, Canada, H4N 1C5
      • Institut de Medecine du sommeil
    • Montreal, Quebec, Canada, H4W 1S7
      • Mount Sinai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• MD diagnosis of obstructive sleep apnea
• No previous use of CPAP
• No concurrent use of hypnotic medication

Exclusion Criteria:

• Fatal comorbidities (i.e., life expectancy less than 6 months)
• Contraindications for CPAP use
• Pregnancy
• Liver Failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Usual sleep apnea and CPAP care Sleep apnea OSR Medical Treatment Plan©	Drug: Placebo; 3.75-7.5mg 14 doses 4 weeks
Experimental: zopiclone; Sleep apnea OSR Medical Treatment plan ©	Drug: Zopiclone; 3.75-7.5mg 14 doses 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CPAP adherence	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
ESS and SAQLI scores, changes from baseline, % time of average CPAP usage over the last month/ self-estimated total sleep time (h). Residual AHI monitored, analysed for similar findings at trial closure and analysis, but is not an efficacy parameter	6 months

Collaborators and Investigators

• Sponsor: OSR Medical Inc.
• Investigators: Principal Investigator: Paul Verschelden, MD DABSM, Cite de la Sante, University of Montreal, OSR Medical, Institut de medecine specialisee de Laval (IMSL); Principal Investigator: Marcel Baltzan, MDCM DABSM, McGill University, OSR Medical, Institut de medecine du sommeil (IMS); Principal Investigator: Kateri Champagne, MD DABSM, McGill University Health Centre (MUHC), OSR Medical, Institut de medecine du sommeil (IMS); Principal Investigator: Germaine Tanzimat, RN, OSR Medical Inc.; Principal Investigator: Barbara Capozzolo, MSc, OSR Medical Inc.

Publications and helpful links

General Publications

• Wolkove N, Baltzan M, Kamel H, Dabrusin R, Palayew M. Long-term compliance with continuous positive airway pressure in patients with obstructive sleep apnea. Can Respir J. 2008 Oct;15(7):365-9. doi: 10.1155/2008/534372.
• Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc. 2008 Feb 15;5(2):173-8. doi: 10.1513/pats.200708-119MG.
• Smith I, Nadig V, Lasserson TJ. Educational, supportive and behavioural interventions to improve usage of continuous positive airway pressure machines for adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007736. doi: 10.1002/14651858.CD007736.
• Lettieri CJ, Shah AA, Holley AB, Kelly WF, Chang AS, Roop SA; CPAP Promotion and Prognosis-The Army Sleep Apnea Program Trial. Effects of a short course of eszopiclone on continuous positive airway pressure adherence: a randomized trial. Ann Intern Med. 2009 Nov 17;151(10):696-702. doi: 10.7326/0003-4819-151-10-200911170-00006.
• Lettieri CJ, Collen JF, Eliasson AH, Quast TM. Sedative use during continuous positive airway pressure titration improves subsequent compliance: a randomized, double-blind, placebo-controlled trial. Chest. 2009 Nov;136(5):1263-1268. doi: 10.1378/chest.09-0811. Epub 2009 Jun 30.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: June 7, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (Estimate): June 9, 2011

Study Record Updates

• Last Update Posted (Estimate): July 17, 2015
• Last Update Submitted That Met QC Criteria: July 16, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Zopiclone
• Other Study ID Numbers: OSRM-0511