Clinical trial NCT02648776: Risk and Benefit Assessment of Hypnotic Agents for Sleep Disorders Among Elderly
Official title: Risk and Benefit Assessment of Hypnotic Agents for Sleep Disorders Among Elderly; A Prospective Cohort Study at a Taiwanese Academic Medical Center
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sleep Disorders
Keywords: hypnotic agents
sleep disorders
elderly
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: National Health Research Institutes, Taiwan
First posted: 2016-01-07
Enrollment: 1400
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Longitudinal prospective observational cohort study

Elderly patients receiving regular outpatient services at China Medical University Hospital

Brief summary: The aims of this study are to (1) examine the medication use patterns of commonly prescribed hypnotics and the factors that were associated with the long-term and short-term use patterns among the elderly population in Taiwan; (2)investigate the associations of using hypnotics with the elderly patients' disease statuses, efficacy and safety, as well as its pharmacokinetic and pharmacogenetic characteristics;(3) determine the clinical, economic and humanistic outcomes of using hypnotics and the corresponding contributing factors for the elderly in Taiwan.

Detailed description: Aging is associated with the changes in the sleep structure, continuity, and timing while it also affects the elderly's physiological and psychological health statuses. Despite the fact that hypnotics are beneficial for the short-term management of insomnia, it is inconclusive about the risk and benefit ratios of long-term use for the elderly. The objectives of this study are to (1)examine the medication use patterns of prescribed hypnotics and the factors that were associated with the use patterns among the elderly population; (2)investigate the associations of using prescribed hypnotics with the elderly patients' disease statuses, efficacy and safety, as well as their pharmacokinetic and pharmacogenetic characteristics;(3)determine the clinical, economic and humanistic outcomes and corresponding factors of using hypnotics for long-term and short-term use in Taiwanese elderly.

This proposed study is the second part of a larger project that consists of two main phases across four years. The first part will include a retrospective database analysis to examine the medication use patterns for sleep disorders and corresponding outcomes using three data sets. Elderly patients aged 65 or older and who received hypnotics for insomnia will be selected from Taiwan's National Health Insurance Research Database, National Health Interview Survey and China Medical University Hospital (CMUH) in-house databases. Focus will be placed on benzodiazepines (BZD) and BZD-receptor specific non-BZD agents (Z-drugs), but Chinese traditional medication used for insomnia will also be examined.

This study is the second part of the larger project. The investigators will conduct a longitudinal, prospective, observational cohort study over a period of two years. The focus of this study is the use of hypnotic BZD and Z-drugs on elderly insomnia patients. The study cohorts include elderly patients, aged 65 years or older, who have received services in the outpatient departments of China Medical University Hospital, Taichung, Taiwan, and who have been prescribed with a selected BZD or Z-drug for insomnia for at least one week. A control group cohort will also be recruited. Each recruited patient will be monitored and evaluated periodically for at least one year. Economic, clinical, and humanistic outcomes, as well as adherence to the hypnotics will be assessed and monitored. Safety and tolerability will be assessed by occurrence of adverse drug reactions. Pharmacokinetic properties and genotyping patterns will be also be evaluated using snapshot blood sampling after the 6th month of enrollment in the study. The clinical and humanistic outcomes measures will include changes in insomnia status, functional status changes, depression status, as well as over-all well-being using EuroQol 5D. Economic evaluation will compare total insurance and out-of-pocket expenses at baseline and at 12 months follow up.

Eligibility criteria: * Inclusion criteria

  1. Patients who have received services in the outpatient departments in CMUH for at least six months persistently before the recruitment,
  2. who are diagnosed with any types of sleep disorders within the outpatient medical records, using ICD-9 codes to identify.
  3. who have been prescribed, for at least one week before the index date of observation, with one of the selected BZD or Z-drugs: estazolam, lorazepam, diazepam, alprazolam, flunitrazepam, zolpidem or zopiclone.
  4. who agree to participate in this observation study and have signed informed consent
* Exclusion criteria

  1. Those elderly patients who were diagnosed with cancers, seizures, specific psychiatric disorders (e.g., dementia, schizophrenia, panic disorder, alcohol withdrawal syndrome) and neurological disorders (e.g., Parkinson) in the baseline and during observation period

Primary outcomes:
measure: Changes from baseline in sleep quality at 12 months
timeFrame: after 12 months of enrollment
measure: Number of participants with an occurrence of associated ADR
timeFrame: after 12 months of enrollment
Secondary outcomes:
measure: Snapshot measurement of plasma drug and drug metabolite concentrations
timeFrame: after 6 months of enrollment
measure: Snapshot measurement of urine drug and metabolite concentrations
timeFrame: after 6 months of enrollment
measure: Calculation of drug clearance using snapshot plasma and urine concentrations
timeFrame: after 6 months of enrollment
measure: Proportion of patients with CYP3A5 mutations
timeFrame: after 6 months of enrollment
measure: Changes from baseline in sleep quality at 6 months
timeFrame: after 6 months of enrollment
measure: Changes from baseline in Barthel Index at 6 months
timeFrame: after 6 months of enrollment
measure: Changes from baseline in Barthel Index at 12 months
timeFrame: after 12 months of enrollment
measure: Changes from baseline in IADL at 6 months
timeFrame: after 6 months of enrollment
measure: Changes from baseline in IADL at 12 months
timeFrame: after 12 months of enrollment
measure: Changes from baseline in EQ-5D-5L & EQ-5D-VAS at 6 months
timeFrame: after 6 months of enrollment
measure: Changes from baseline in EQ-5D-5L & EQ-5D-VAS at 12 months
timeFrame: after 12 months of enrollment
measure: Changes from baseline in MMAS-8 after 6 months
timeFrame: after 6 months of enrollment
measure: Changes from baseline in MMAS-8 after 12 months
timeFrame: after 12 months of enrollment
measure: Change from baseline in economic healthcare costs using NHI and out-of-pocket expenses at 12months
timeFrame: At 12 months after enrollment
measure: Changes from baseline in insomnia at 6 months
timeFrame: After 6 months of enrollment
measure: Changes from baseline in insomnia at 12 months
timeFrame: After 12 months of enrollment
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: China Medical University Hospital
Study officials:
affiliation: Pharmacist, Associate Professor
name: Hsiang-Wen Lin, PhD
role: PRINCIPAL_INVESTIGATOR
References: