Trazodone Dose and the Risk of Serious Adverse Events in Older Adults With Low Kidney Function: A Population-Based Cohort Study Research Protocol
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 31,459
- 试验地点
- 1
- 主要终点
- Number of participants with a composite outcome of all-cause hospitalization or all-cause emergency department visit, or all-cause mortality.
研究概览
简要总结
This is a population-based retrospective, new-user, active comparator cohort study assessing whether initiating a new outpatient prescription of trazodone (>75-150 mg/day), compared to a lower dose (25-75 mg/day) is associated with an increased 30-day risk of serious adverse events among older adults with low kidney function estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m², who are not receiving dialysis and have no history of kidney transplantation.
The primary outcome is a 30-day composite of all-cause hospitalization, all-cause emergency department visit, or all-cause mortality.
详细描述
*Summary*
Background:
Trazodone is a triazolopyridine antidepressant classified as a serotonin antagonist and reuptake inhibitor. It antagonizes serotonin 5-hydroxytryptamine (5-HT) 2A and 5-HT2C receptors, weakly inhibits serotonin reuptake, and also antagonizes alpha-1-adrenergic and histaminergic receptors. The U.S. Food and Drug Administration has approved trazodone for the treatment of major depressive disorder, and it is commonly prescribed off-label for insomnia, especially in older adults.
Trazodone is metabolized by the liver and excreted through the kidneys as an inactive metabolite. In patients with low kidney function, especially older adults, trazodone can accumulate and increase the risk of serious adverse events.
The most common measure to assess kidney function in routine clinical care is the estimated glomerular filtration rate (eGFR), expressed in lab reports as mL/min/1.73 m2. A normal eGFR is >90 mL/min/1.73 m2, and a value <45 mL/min/1.73 m2 is considered to be low.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 66 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The cohort will will include all older adults (≥66 years) with an eGFR <45 mL/min per 1.73 m2 (not receiving dialysis or having a history of kidney transplantation) who received a new outpatient prescription for oral trazodone with an initial dose between 25 and 150 mg/day and a day supply of ≥5 days between January 1, 2008 to March 1,
- •The age criterion is set to guarantee that individuals in this population have had at least one year of prior prescription drug coverage. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once.
排除标准
- •Individuals with missing administrative database number, missing or invalid age (<0 or >105 years), missing or invalid sex, death on or before the index date, non-Ontario resident (for Ontario data), or non-Alberta residents (for Alberta data).
- •Individuals less than 66 years of age on the index date.
- •Those with evidence of any study drug prescription 180 days before the index date (to restrict to new users only).
- •Individuals with more than one study drug prescription on the index date, as this complicates the ability to ascertain the prescribed dose accurately.
- •Individuals with end-stage renal disease, chronic dialysis, or a kidney transplant prior to the index date.
- •Evidence with hospital discharge or emergency department visit in the two days prior to or on the index date to ensure a new outpatient prescription.
- •Individuals with no serum creatinine lab value in the 0-365 days prior to the index date.
- •Individuals with unstable baseline kidney function:
- •If the most recent serum creatinine test prior to the index date was an inpatient test [ER or hospitalization] <refer to this as test date 1>, and there is not at least one 'outpatient' serum creatinine in the year before test date 1, OR If the most recent prior serum creatinine test prior to the index date was an inpatient test [ER or hospitalization] <refer to this as test date 1>, and while there is at least 'outpatient' serum creatinine test in the year before <test date 1>, the most recent outpatient test prior to <test date 1> differs by an eGFR 10 mL/min/1.73 m2 or more from the value on <test date 1>.
- •In Ontario, it has been shown that outpatient serum creatinine measurements in the province, conducted on a single occasion, indicate stable values.
- •Individuals receiving palliative care in the 0-365 days prior to the index date, in this setting, dosing is less relevant; rather, the focus is comfort care.
- •The investigators restrict to the first prescription in individuals with more than one eligible prescription. Date of this prescription will be the index date (the Date from which the outcomes start being assessed).
研究组 & 干预措施
Low dose (25-75 mg/day) Trazodone
Residents of Ontario, aged 66 years or older with low kidney function (estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m² but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for trazodone (low dose 25-75 mg/day) with a day supply ≥ 5 days at an outpatient pharmacy under Ontario Drug Benefit (ODB) program from January 1, 2008, to March 1, 2025. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. If the investigators conduct the study in Alberta, the accrual period for Alberta will be determined.
干预措施: Trazodone HCl (Drug)
High dose (>75-150 mg/day) Trazodone
Residents of Ontario, aged 66 years or older with low kidney funciton (estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m² but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for trazodone (high dose >75-150 mg/day) at an outpatient pharmacy with a day supply ≥ 5 days under Ontario Drug Benefit (ODB) program from January 1, 2008, to March 31, 2025. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once. If the investigators conduct the study in Alberta, the accrual period for Alberta will be determined.
干预措施: Trazodone HCl (Drug)
结局指标
主要结局
Number of participants with a composite outcome of all-cause hospitalization or all-cause emergency department visit, or all-cause mortality.
时间窗: Older adults exposed to high-dose (>75-150 mg/day) versus low-dose (25-75 mg/day) trazodone will enter the cohort and be followed until the study outcome (first event), death, or 30 days from the cohort entry date.
All-cause hospitalization, all-cause emergency visits, and all-cause mortality will be combined into a composite measure. Only the first hospitalization or first emergency department visit occurring within 30 days after the cohort entry date will be considered.
次要结局
- Number of participants with all-cause hospitalization.(Older adults exposed to high-dose (>75-150 mg/day) versus low-dose (25-75 mg/day) trazodone will enter the cohort and be followed until the study outcome (first event), death, or 30 days from the cohort entry date.)
- Number of participants with all-cause emergency department visit.(Older adults exposed to high-dose (>75-150 mg/day) versus low-dose (25-75 mg/day) trazodone will enter the cohort and be followed until the study outcome (first event), death, or 30 days from the cohort entry date.)
- Number of participants with all-cause mortality(Older adults exposed to high-dose (>75-150 mg/day) versus low-dose (25-75 mg/day) trazodone will enter the cohort and be followed until the study outcome (first event), death, or 30 days from the cohort entry date.)
- 30-day composite outcome of a hospital encounter with fragility fracture, falls, hypotension, or syncope.(Older adults exposed to high-dose (>75-150 mg/day) versus low-dose (25-75 mg/day) trazodone will enter the cohort and be followed until the study outcome (first event), death, or 30 days from the cohort entry date.)
- 30-day composite outcome of a hospital encounter with delirium, encephalopathy, or hospital admission with receipt of an urgent computed tomography scan of the head(Older adults exposed to high-dose (>75-150 mg/day) versus low-dose (25-75 mg/day) trazodone will enter the cohort and be followed until the study outcome (first event), death, or 30 days from the cohort entry date.)
- 30-day hospital encounter composite of atrial fibrillation/flutter, ventricular arrhythmia/sudden cardiac death, and other arrhythmia.(Older adults exposed to high-dose (>75-150 mg/day) versus low-dose (25-75 mg/day) trazodone will enter the cohort and be followed until the study outcome (first event), death, or 30 days from the cohort entry date.)