Pharmacological Treatment of Insomnia in Palliative Care

Pharmacological Treatment of Insomnia in Palliative Care: A Randomized, Double-blind, Placebo Controlled, Parallel-group, Multicenter Trial Investigating the Short Time Effect of Zopiclone on Self-reported Sleep Quality in Patients With Advanced Cancer Who Use Opioids and Who Report Insomnia

Sleep disturbance is frequent in patients with advanced cancer and decreases the tolerability of other symptoms and impairs quality of life. A detailed description of sleep disturbance and its association with other symptoms, and intervention studies on sleep medications are scarce in patients with advanced cancer. A well-designed randomized controlled trial is needed to determine the short time effectiveness of zopiclone on sleep quality, one of the currently available therapies of insomnia, and further to contribute to the clinical management of insomnia in patients with advanced cancer.

Study Overview

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

Detailed Description

The clinical trial is a randomized, double-blind, placebo controlled, parallel-group, multicenter trial investigating the short time effectiveness of zopiclone on self-reported sleep quality in patients with advanced cancer who use opioids and who report insomnia. Patients with advanced cancer who use opioids and who report insomnia are randomized to either a hypnotic, zopiclone (Arm A) or placebo (Arm B) for six nights. For this study zopiclone Actavis 3.75 mg, 5 mg and 7.5 mg (active comparator) and placebo are defined as Investigational Medicinal Products. The initial dose is zopiclone/placebo 3.75 mg/day. Evaluation of sleep quality is performed in the morning after night 2 and 4 with evaluation of sleep quality by using a numerical rating scale 0-10 with the question "Please circle the number that best describes how you feel now" 0= Best sleep, 10= Worst possible sleep.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, 5892
    • Sunniva senter for lindrende behandling, Haraldsplass Diakonale sykehus
  • Levanger, Norway, 7601
    • Sykehuset Levanger
  • Skien, Norway, 3710
    • Helse Sør-Øst RHF, Sykehuset i Telemark,
  • Trondheim, Norway, 7006
    • St. Olavs Hospital
  • Tønsberg, Norway, 3103
    • Helse Sør-Øst RHF, Sykehuset i Vestfold,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically verified malignant disease
2. Presence of metastatic / disseminated disease

3. Presence of insomnia syndrome defined as:

   1. Self-reported difficulty with initiating sleep (greater than 30 minutes to sleep onset) and/or difficulty maintaining sleep (greater than 30 minutes nocturnal waking time); and
   2. Sleep difficulty at least 3 nights per week; and
   3. Sleep difficulty that causes significant impairment of daytime functioning (The patient will be asked if sleep difficulty result in altered daytime function i.e. feeling tired, lack of energy)
4. Able to comply with all study procedures
5. Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations.

Exclusion Criteria:

1. On-going treatment or previous treatment (within last 4 weeks) for more than consecutive 3 days with medications given for insomnia
2. Adverse reactions to zopiclone
3. History of substance abuse
4. Concomitant use of rifampicin and erythromycin

5. Any other contraindication listed on the summary of product characteristics of the investigated medicinal product:

   1. Myasthenia gravis
   2. An established diagnosis of Severe impairment of respiratory function
   3. An established diagnosis of Severe hepatic insufficiency.(Child-Pugh grade B or C)
   4. An established diagnosis of sleep apnea
   5. Known hypersensitivity to the drug or to any component in its formulation: Lactose monohydrate, Calcium hydrogen phosphate, Maize starch, Croscarmellose sodium, Magnesium stearate, Titanium dioxide (E 171), Hypromellose, Iron oxide yellow/Iron oxide red (E 172) and Macrogol
6. Unfit for participation for any reason as judged by the investigator
7. Pregnancy or lactation
8. Women of reproductive age not willing or unable to employ an effective method of contraception (sterilization, using IUD or oral contraception)
9. Scheduled surgery within the next week
10. In the need of change in scheduled opioid dose at baseline (study visit 1)
11. Scheduled intravenous administration of chemotherapy during the study period (from baseline to day 8) or intravenous administration of chemotherapy during the last week
12. Change in corticosteroid dose last week before baseline or planned dose change in corticosteroid dose within 7 days from baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zopiclone; Zopiclone six nights	Drug: Zopiclone
Placebo Comparator: Placebo; Placebo six nights	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported sleep quality	Primary endpoint is patient-reported sleep quality during the final study night (night six) assessed on a numerical rating scale (NRS) 0-10. 0= Best sleep, 10=Worst possible sleep.	Night six (last study night)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported total sleep time		Night six (last study night)
Patient reported sleep onset latency	Sleep onset latency (how long (minutes) it takes to fall asleep	Night six (last study night)

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Norwegian University of Science and Technology
• Investigators: Principal Investigator: Pål Klepstad, St. Olavs Hospital

Publications and helpful links

General Publications

• Jakobsen G, Engstrom M, Paulsen O, Sjue K, Raj SX, Thronaes M, Hjermstad MJ, Kaasa S, Fayers P, Klepstad P. Zopiclone versus placebo for short-term treatment of insomnia in patients with advanced cancer: study protocol for a double-blind, randomized, placebo-controlled, clinical multicenter trial. Trials. 2018 Dec 27;19(1):707. doi: 10.1186/s13063-018-3088-3.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2016
• Primary Completion (Actual): July 13, 2021
• Study Completion (Actual): July 13, 2021

Study Registration Dates

• First Submitted: June 17, 2016
• First Submitted That Met QC Criteria: June 20, 2016
• First Posted (Estimate): June 21, 2016

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: July 14, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Palliative Care; zopiclone
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Zopiclone
• Other Study ID Numbers: SleepRCT_270215; 2015-005306-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No