pErsonalised Nocebo Assessment of Beta-blockEr Symptoms in Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Nocebo Fraction
研究概览
简要总结
Beta-blocker tablets are an effective treatment for heart failure that make people live longer and reduce the need to be admitted to hospital. Many patients who are at high risk of death are prescribed beta-blockers, but later choose to stop taking them because of symptoms that they perceive to be side-effects. Some patients' symptoms may genuinely be side-effects due to the beta-blocker tablets, but, in reality, many of the symptoms which may lead to people stopping beta-blockers are actually experienced at similar rates compared to placebo. The symptoms may be caused by heart failure itself, or the expectation that they will have a side effect when they take a tablet (the nocebo effect). There is a need to be able to identify the majority of patients who aren't actually having side-effects so that they can restart beta-blockers and not miss out on life-prolonging treatment. To answer this question reliably and with high precision requires a personalised approach with an 'N-of-1' study. This study will measure participants' symptoms in three scenarios: taking a beta-blocker tablet (bisoprolol 2.5mg) or a placebo tablet or no study medication in a randomised order.
The primary aim of this study is to determine, for an individual, whether the adverse effects of beta-blockade in heart failure are genuine. Specifically, the objectives are:
- To determine the proportion of a patient's symptoms that are due to taking beta-blocker tablets, and the proportion that are due to the expectation that the treatment will cause symptoms (the nocebo effect).
- To determine whether, on average, symptoms are worse when taking beta-blocker compared to placebo tablets or no treatment.
- To determine whether on average symptom intensity associated with beta-blockade decreases after receiving a report on how much of their symptoms are due to the beta-blocker.
Throughout the protocol participants report daily the intensity of the symptom that previously led to their beta-blocker cessation via a smartphone app. Participants will report weekly their adherence, general heart failure symptoms and quality of life. In this way the investigators will discover, for an individual patient, the proportion of their symptom that is due to the beta-blocker tablet, and whether knowing their personalised results helps them to restart beta-blocker tablets.
详细描述
Method:
ENABLE-HF is a prospective, N-of-1 randomised study of symptoms in participants with HFrEF. The study population will be patients who have an indication for oral beta-blockade due to HFrEF, and are currently not taking any beta-blockers licenced for HFrEF, having previously tried and stopped taking them due to perceived symptoms that they and/or their clinician(s) attributed to the beta-blocker(s).
Participants' suitability will be assessed by a detailed clinical history, clinical examination and review of their medical history to confirm the diagnosis of HFrEF, indication for beta-blocker therapy and that they are currently not taking it. The inclusion and exclusion criteria will be applied. At enrolment, a researcher will generate and allocate an unused randomisation code to the participant. This will also determine the contents of their 9 study bottles to be taken in Phase 2. The participant will then be provided with packs containing all phases' medications, and a smartphone if required.
The study protocol has three main phases:
(i) Phase 1 - a two week, open-label period of 2.5mg bisoprolol daily
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Heart failure with index LVEF <40%
- •Not currently taking beta-blocker tablets
- •Previously tried one of beta-blocker tablet, and stopped taking it due to symptoms attributed to the beta-blocker
- •Consenting to participate in the study
排除标准
- •Documented anaphylaxis to beta-blockers
- •Clinical contraindication to Bisoprolol including (but not limited to):
- •Asthma requiring BTS treatment step 3 or higher
- •Marked bradycardia (<50 bpm)
- •Symptomatic hypotension (systolic BP <85mmHg)
- •Metabolic acidosis
- •Phaeochromocytoma
- •1st degree heart block with PR interval >250ms
- •2nd degree or complete heart block
- •Sick sinus syndrome
- •Acute pulmonary oedema
- •Life expectancy <1 year
- •Patient refusal or inability to participate in the study
研究组 & 干预措施
Blinded bisoprolol tablets
The protocol includes a randomised, blinded nine week phase in which participants take either bisoprolol, no tablets or placebo. They will be randomly assigned to take three weeks in total of blinded bisoprolol tablets.
干预措施: Bisoprolol 2.5 mg (Drug)
Blinded placebo
Participants will be randomly assigned to take three weeks of blinded placebo tablets. They will be unaware as to whether they are consuming bisoprolol or placebo in this phase.
干预措施: Placebo (Drug)
结局指标
主要结局
Nocebo Fraction
时间窗: From start of protocol to end of second open-label beta-blocker phase, an average of 15 weeks
For each participant, we will primarily calculate the 'nocebo fraction'. This is a measure of the proportion of an individual patient's symptoms which are due to beta-blocker and which are due to the nocebo effect. It is calculated by measuring and averaging the daily symptom intensity (scored from 0 to 100) when taking: \[A\] beta-blocker tablet \[B\] placebo (blank) tablet \[C\] no tablet
次要结局
- Difference in Symptom Intensity Scores Between Beta-Blocker and Placebo(From start of protocol to end of second open-label beta-blocker phase, an average of 15 weeks)
- Change in Symptom Intensity Scores after Receiving n-of-1 Personalised Results(From start of protocol to end of second open-label beta-blocker phase, an average of 15 weeks)