A Randomised Controlled Cross-over Trial to Evaluate Evening Versus Morning Administration of a Cardiovascular Polypill
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- UMC Utrecht
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- LDL cholesterol (polypill evening vs polypill morning)
研究概览
简要总结
Background and rationale:
In clinical practice, antihypertensives are generally prescribed for use in the morning, whereas some statins are recommended for use in the evening. There is evidence that the reduction in LDL cholesterol achieved with some statins is superior when taken in the night, but it is unclear whether the additional reduction in LDL cholesterol(and the reported improvement in BP control when aspirin is taken in the evening) is offset by a reduction in adherence when taking medication in the evening. Current product labelling recommends night use for simvastatin and does not state a timing preference for aspirin or blood pressure lowering medicines. There is therefore uncertainty concerning the best timing of administration of the polypill. This uncertainty will be addressed by this trial.
Trial design:
Randomised, open label cross over trial (n=75) of the polypill in the morning compared with the evening administration compared with individual agent administration (acetylsalicylic acid and blood pressure lowering agents in the morning, and statin in the evening) in individuals at high risk of cardiovascular disease. Patients will be recruited to the RHP 2c (acetylsalicylic acid 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorthiazide 12.5mg), and will be randomly allocated to the sequence of time of administration.
详细描述
Background and rationale:
In clinical practice, antihypertensives are generally prescribed for use in the morning, whereas some statins are recommended for use in the evening. There is evidence that the reduction in LDL cholesterol achieved with some statins is superior when taken in the night, but it is unclear whether the additional reduction in LDL cholesterol(and the reported improvement in BP control when aspirin is taken in the evening) is offset by a reduction in adherence when taking medication in the evening. Current product labelling recommends night use for simvastatin and does not state a timing preference for aspirin or blood pressure lowering medicines. There is therefore uncertainty concerning the best timing of administration of the polypill. This uncertainty will be addressed by this trial.
Trial design:
Randomised, open label cross over trial (n=75) of the polypill in the morning compared with the evening administration compared with individual agent administration (acetylsalicylic acid and blood pressure lowering agents in the morning, and statin in the evening) in individuals at high risk of cardiovascular disease. Patients will be recruited to the RHP 2c (acetylsalicylic acid 75mg, simvastatin 40mg, lisinopril 10mg, hydrochlorthiazide 12.5mg), and will be randomly allocated to the sequence of time of administration.
Aim:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant is able to give informed consent.
- •The trial Investigator considers that each of the polypill components are indicated at the doses in the Red Heart Pill
- •Established atherothrombotic cardiovascular disease (CVD) or intermediate to high cardiovascular risk, defined as;
- •History of coronary heart disease (myocardial infarction, stable or unstable angina pectoris, or coronary revascularisation procedure), or
- •History of ischaemic cerebrovascular disease (ischaemic stroke or transient ischaemic attack), or
- •History of peripheral vascular disease (peripheral revascularisation procedure or amputation due to vascular disease or aortic reconstruction), or
- •For individuals without established cardiovascular disease, a calculated 5 year CVD risk of 5% or greater (calculated using the 1991 Anderson Framingham risk equation with adjustments as defined by the New Zealand Guidelines Group recommendations - (Appendix 1))
排除标准
- •Contraindication to any of the components of the polypill (e.g. known intolerance to aspirin, statins, or ACE inhibitors; pregnancy or likely to become pregnant or breastfeeding women during the treatment period). Such contraindications are fully listed in the Investigator Brochures.
- •The treating doctor considers that changing a participant's cardiovascular medications would put the participant at risk (e.g. symptomatic heart failure, high dose β-blocker required to manage angina or for rate control in atrial fibrillation, accelerated hypertension, severe renal insufficiency, a history of severe resistant hypertension).
- •Other potential reasons for exclusion include:
- •Known situation where medication regimen might be altered for a significant length of time, e.g. current acute cardiovascular event, planned coronary bypass graft operation.
- •Unlikely to complete the trial (e.g. life-threatening condition other than cardiovascular disease) or adhere to the trial procedures or attend study visits (e.g. major psychiatric condition, dementia).
- •Any reason, medical condition, ongoing medication or significant disability that would prevent the participant complying with trial consent, treatment and follow-up procedures or potentially jeopardise her / his medical care.
- •Night shift workers.
研究组 & 干预措施
Polypill in the morning
Cardiovascular agents in a polypill used from 05.00-11.00 in the morning (acetylsalicylic acid 75 mg, simvastatin 40 mg, lisinopril 10 mg, hydrochlorothiazide 12,5 mg)
干预措施: Cardiovascular Agents (Drug)
Polypill in the evening
Cardiovascular agents in a polypill used from 18.00-00.00 in the evening (acetylsalicylic acid 75 mg, simvastatin 40 mg, lisinopril 10 mg, hydrochlorothiazide 12,5 mg)
干预措施: Cardiovascular Agents (Drug)
Individual agents of the polypill)
Cardiovascular agents in as acetylsalicylic acid 75 mg, lisinopril 10 mg, hydrochlorothiazide 12,5 mg used 05.00-11.00 in the morning.
Simvastatin 40 mg used 18.00-00.00 in the evening.
干预措施: Cardiovascular Agents (Drug)
结局指标
主要结局
LDL cholesterol (polypill evening vs polypill morning)
时间窗: 24 weeks
Differences between polypill in the evening (after 8 weeks of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) in: - Mean LDL cholesterol
Mean 24 hour ambulatory systolic BP (polypill evening vs morning)
时间窗: 24 weeks
Difference between the between polypill in the evening (after 8 weeks of evening treatment) and polypill in the morning (after 8 weeks of morning treatment) in: - Mean 24 hour ambulatory systolic BP
次要结局
- Differences in ambulatory BP parameters after a mean of 7 week of treatment (polypill evening vs. morning, polypill vs regular care)(24 weeks)
- Differences in tolerability (adverse event, cessation of treatment)(Every 6-8 weeks)
- Adherence (polypill evening vs. morning, polypill vs regular care)(24 weeks)
- Cholesterol fractions (polypill evening vs. morning, polypill vs regular care)(24 weeks)
研究者
dr.Frank L.J. Visseren
Clinical Professor
UMC Utrecht