Effects of Discontinuation of Levothyroxine Treatment in Older Adults: a Self-controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 513
- 试验地点
- 1
- 主要终点
- Proportion of participants successfully withdrawn from levothyroxine treatment
研究概览
简要总结
Many older persons use the thyroid hormone levothyroxine which is often continued for life. Scientifically, there is much uncertainty whether simple continuation is the optimal approach. The goal of this self-controlled observational study is to investigate how many participants of 60 years and older who are currently using levothyroxine, can be successfully withdrawn from levothyroxine treatment, either fully or partially, while maintaining a normal thyroid function (defined as a free T4 level within the reference range and a thyroid stimulating hormone [TSH] level <10 mU/L), 52 weeks after the start of the discontinuation.
Levothyroxine treatment is discontinued gradually guided by the participant's general practitioner, using a step-wise approach with regular monitoring of thyroid function. In addition, the effects of discontinuation of levothyroxine on thyroid-specific quality of life and general health will be studied using questionnaires.
详细描述
Study design - This is a self-controlled trial investigating the stepwise discontinuation of levothyroxine treatment in adults aged 60 years and older with a follow-up of 1 year. Outcomes will be measured 12 weeks before the start of discontinuation, at the start of discontinuation, at 6 weeks, at the end of discontinuation, and after 52 weeks. The outcomes will be compared within participants.
Study phases
- This study consists of 3 phases: a control phase of 12 weeks (T-12 to T0), the discontinuation phase (minimum of 6 weeks, maximum of 36 weeks; T0 to Tx), and a follow-up phase (from the end of discontinuation till 52 weeks after the start of discontinuation; Tx to T52).
- Control phase: participants enter the study during a control period with pre-baseline measurements of thyroid function and secondary outcome parameters to determine natural variation after which treatment with levothyroxine is continued per usual care for at least 12 weeks. Participants with a pre-baseline TSH level ≥10 mU/L do not proceed to the discontinuation phase.
- Discontinuation phase: this phase starts with baseline measurements of thyroid function and secondary outcome parameters, followed by a consultation of the participant with their GP during which discontinuation of levothyroxine is initiated, except when TSH level ≥10 mU/L. Levothyroxine is discontinued stepwise, and at intervals of ≥ 6 weeks to ascertain a steady-state concentration has been reached before the following control visit. During each '6-week' visit, the GP evaluates thyroid function and symptoms with the participant. Upon agreement, the daily dose of levothyroxine can then be lowered provided thyroid function is within the predefined limits, i.e. a normal fT4 and TSH < 10 mU/L. With each step, the dose of levothyroxine is reduced by approximately 25 mcg. The discontinuation phase ends after the evaluation of complete withdrawal of the levothyroxine treatment (i.e. 6 weeks after the final discontinuation step). Secondary outcome parameters are collected at the first '6-week' visit and the end of discontinuation.
- Follow-up phase: this phase ends with a final visit 52 weeks after the start of the discontinuation phase and includes the assessment of thyroid function, current dose of levothyroxine, and secondary outcome parameters.
Sample size
- The sample size calculation is based on the primary outcome, the proportion of participants successfully stopping levothyroxine treatment between baseline and final follow-up at 52 weeks. The investigators estimated a proportion of 50% of the participants would successfully discontinue levothyroxine treatment. A sample size of 385 participants was chosen because this allows to estimate the expected proportion of 50% with a 95% confidence interval of which the lower and upper limit is expected to deviate by 5 percentage points from the found percentage (i.e. 45% to 55% when the found percentage is indeed 50%). Taking a maximum of 25% loss to follow up into account over the duration of 15 months (exclusion at T-12 when TSH level ≥ 10 mU/L and/or fT4 below reference range, withdrawal, moving away, or death between T-12 and T52) a maximum of 513 participants will be recruited.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 60 years or over (≥ 60 years)
- •Using any levothyroxine mono-therapy medicament (ATC: H03AA01) continuously for a minimum of 1 year with stable dose of levothyroxine.
排除标准
- •Last measurement of TSH ≥10 mU/L during levothyroxine treatment
- •Current reason for levothyroxine treatment: patients with history of thyroidectomy; radioactive iodine treatment or neck irradiation; congenital hypothyroidism; secondary hypothyroidism, or concurrent amiodarone or lithium use
- •Dose of treatment; for safety issues, patients using > 150 mcg levothyroxine per day will not be eligible
- •Concurrent treatment with liothyronine (the synthetic form of thyroid hormone T3), thiamazole, carbimazole or propylthiouracil (inhibitors of T3 and T4 synthesis).
- •Diagnosis of heart failure NYHA grade IV
- •Participation in ongoing trials of therapeutic interventions
- •Life-expectancy of less than 6 months
- •Diagnosis of dementia
- •Incapacitated adults
- •Persons that plan to move out of the region in which the study is being conducted in the next months.
结局指标
主要结局
Proportion of participants successfully withdrawn from levothyroxine treatment
时间窗: 52 weeks after start of discontinuation
The proportion of participants that withdraw from levothyroxine treatment successfully (defined as normal fT4 levels and TSH levels \<10 mU/L) at 52 weeks after the start of the discontinuation.
次要结局
- Effect of levothyroxine discontinuation on thyroid-related quality of life(52 weeks after start of discontinuation)
- Proportion of participants who achieve a substantial dose reduction of levothyroxine(52 weeks after start of discontinuation)
- Effect of levothyroxine discontinuation on self-rated health(52 weeks after start of discontinuation)
- Reflection of participants on the decision to discontinue levothyroxine treatment(52 weeks after start of discontinuation)
- Effect of levothyroxine discontinuation on general health(52 weeks after start of discontinuation)
研究者
jgussekloo
Professor in primary care
Leiden University Medical Center