1、11.1BMC Family Practice IF：2.032一个实用临床试验的原理和设计，以评估家庭血压监测和降压药自滴定对控制不良的高血压的影响摘要：Lack of control of hypertension is one of the most prevalent problems encountered by general practitioners (GPs). Self-measured blood pressure monitoring at home (SMBP) and self-titration of medication could be a good stra
2、tegy to improve hypertension management, however, evidence is limited and not conclusive. We aimed to assess the effectiveness, in the primary care setting, of an intervention that includes educational components, SMBP and self-titration of antihypertensive medication to decrease systolic blood pres
3、sure compared to usual care, in a population with poorly controlled hypertension, during a 12-month period.背景:高血压控制不足是全科医生遇到的最普遍的问题之一。家庭自测血压(SMBP)和药物自滴定可能是改善高血压管理的一个好策略，然而，证据有限，没有结论性。我们的目的是评估在基层医疗机构中，在高血压控制不足的人群中，相比于常规治疗，包含教育、SMBP 和自滴定降压药的干预措施在 12 个月内降低收缩压的效果。Methods: Pragmatic, controlled, randomiz
4、ed, unblinded clinical trial with two parallel groups assigned in a ratio of 1:1 to self-management (which includes educational components, SBMP and self-titration of antihypertensive medication based on a patient s GP s pre-established adjustment plan) or to usual care (with educational components
5、too)方法:采用实用的 、随机对照非盲的临床试验，将两平行组按 1:1 的比例分配给自我管理组(其中包括教育成分、SBMP和基于患者的家庭医生预先制定的调整计划自我滴定降压药）或常规护理组(也包括教育成分)。Discussion: If the data from this trial show positive results, the study may contribute to a change of strategy in the treatment of hypertension, focusing on the patient as the main actor to achi
6、eve blood pressure control. Furthermore, this approach might contribute to the financial sustainability of the National Health Service讨论:如果本试验数据显示为阳性，本研究可能有助于改变高血压治疗策略，以患者为主要角色控制血压。此外，这种做法可能有助于国家卫生服务的财政可持续性。试验注册:本试验已在数据库中注册，编号 EudraCT: 2016-003986-25。2017 年 5 月 5 日注册关键词:自我监测 ;血压;高血压；自我滴定；基层医疗；实用的临床试
7、验背景：The presence of hypertension is one of the most important issues in the global burden of disease 1. In developed countries, the degree of control of hypertension has increased progressively over the last 15 years and has contributed to a decline in cardiovascular morbidity and mortality 2 8. How
8、ever, a recent study carried out in 12 European countries showed that more than 50% of patients treated for hypertension continued to have uncontrolled blood pressure (BP) 9 and that results are far from ideal. As a large part of hypertension management is carried out in primary care (PC) and it is
9、one of the most prevalent problems encountered by General Practitioners (GP), interventions aimed at improving its management should preferably be made in this setting. Recent hypertension clinical guidelines put emphasis on self-measured blood pressure monitoring (SMBP) by patients and on team-base
10、d systems to manage the condition 10.高血压的存在是全球疾病负担1中最重要的问题之一 。在发达国家，高血压的控制程度在过去 15 年中逐步提高，心血管发病率和死亡率下降2-8。然而，最近在 12 个欧洲国家进行的一项研究表明， 50%以上接受高血压治疗的患者仍然无法控制血压(BP)9 ，这一结果远非理想。由于高血压管理的很大一部分是在基层医疗(PC)中进行的，它是全科医生遇到的最普遍的问题之一，因此改善管理的干预在这种机构下进行可能更好。最近的高血压临床指南强调由患者在家庭自行测量血压(SMBP)和基于团队的系统来管理10。Self-measured blo
11、od pressure monitoring at home (SMBP) is practiced extensively nowadays. In the United Kingdom and Canada it is highly recommended by GPs and used by more than 30% of patients 11, 12. Systematic reviews have shown disparate information regarding the effectiveness of SMBP alone in reducing blood pres
12、sure (BP). On the other hand, self-monitoring in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counseling) has been shown to lead to clinically significant BP reduction, which persists for at least 12 months
13、. Nevertheless, the effectiveness of SMBP requires additional evaluation given that its definition in those studies is highly heterogeneous (different clinical protocols, different strategies for additional support and management) and given the fact that most studies have short follow-ups (1 year or
14、 less) 13, 14.目前家庭自测血压广泛应用。在英国和加拿大，全科医生高度推荐它（家庭自测血压），超过 30%的患者使用11,12。系统评价显示单独 SMBP 降低血压(BP)有效性的不同信息。另一方面，自我监测与联合干预相结合( 包括医生、药剂师或患者的系统药物滴定; 教育; 或者生活方式咨询)已经被证明会引起显著临床意义的血压下降，至少持续12 个月。然而，鉴于 SMBP 在那些研究中的定义高度异质性( 不同的临床方案，不同的额外支持和管理策略 )，并且考虑到大多数研究的随访时间较短(1 年或更短 )，SMBP 的有效性需要额外的评估 13,14。Regarding home ti
15、tration of antihypertensive medication, evidence is more limited and shows mixed results. Two clinical essays, the TASMINH2 15and the TASMINH-SR16, both in the United Kingdom and developed in the primary care setting by the same research team, are some of the most recent and interesting clinical tri
16、als carried out in this field. In these studies, SMBP together with self-titrate medications (according to a previously agreed plan), combined with telemedicine components, was compared with usual care. In both studies systolic blood pressure (SBP) decreased from baseline to 12 months, with signific
17、ant differences between the intervention and control group (5.4 and 9.2 mmHg, respectively). Frequency of side effects was similar in both groups 15, 16. The TASMINH-SR study is of special relevance because it was carried out with high risk patients (with a personal history of stroke, ischemic cardi
18、opathy, diabetes or kidney failure), a population of special interest to achieve BP targets 16. On the other hand, a clinical trial carried out in the US in a low-income, predominantly minority population, aimed to determine whether health coaching, SMBP and home titration of antihypertensive medica
19、tions could improve BP control compared with SMBP and health coaching alone. The results showed that both the home-titration arm and the nohome-titration arm had a reduction in SBP, with no significant differences between them from baseline to 6 months 17.关于降压药的家庭滴定，证据更有限，结果不一。两篇临床论文，TASMINH215和 TAS
20、MINH-SR16，都在英国，由同一研究小组在基层医疗环境下进行的，是在这个领域最新和令人关注的临床试验。在这些研究中，将 SMBP 和自滴定药物( 根据先前商定的计划 )，以及远程医疗成分，与常规治疗进行比较。在这两项研究中，从基线到 12 个月收缩压(SBP) 在干预组和对照组之间下降有显著差异(分别为 5.4mmHg 和 9.2 mmHg)。两组不良反应发生频率相似15,16。TASMINH-SR 研究之所以具有特殊意义，是因为它是针对高风险患者(有中风、缺血性心脏病、糖尿病或肾衰竭的个人病史) 进行的，而这些患者对达到 BP 目标16特别感兴趣。另一方面，美国在一个以少数族裔为主的低收
21、入人群中进行了一项临床试验，目的是确定，与单独进行 SMBP 和健康指导相比，健康指导、SMBP 和降压药家庭滴定是否能改善血压控制。结果表明，家庭滴定和非家庭滴定 SBP 均有降低，从基线到 6 个月17无显著差异。Finally, when interpreting hypertension studies over time, it is important to procede with caution, as the definition of the condition changes almost with every update of guidance. For instan
22、ce, earlier versions of guidelines such as those of the the Joint National Committee (JNC) and of the European Society of Hypertension (ESH)/European Society of Cardiology (ESC), suggested more restrictive BP control objectives than recent versions (especially in patients over 60 years old, diabetic
23、s and patients with renal failure) 18-20. These objectives may be modified again in the light of the results of recent studies 21 23.最后，随着时间的推移，在解释高血压研究时，必须谨慎行事，因为这种情况的定义几乎随着指南的更新而改变。例如, 早期版本的指南如联合国委员会的 (JNC)和欧洲高血压协会（ESH）/欧洲心脏病学会(ESC)的,相比最新的指南，提出更加严格的血压控制目标(特别是在 60 岁以上患者,糖尿病患者和肾衰患者 )18-20。根据最近的研究结果，
24、这些目标可能会再次修改21 23。研究目的The primary aim of the ADAMPA TRIAL is to assess the effectiveness, in the primary care setting, of an intervention that includes educational components, SMBP and self-titration of antihypertensive medication to decrease SBP compared to usual care, in a population with poorly co
25、ntrolled hypertension, during a 12-month period. In addition, an extension with passive follow-up is planned for 24 months, collecting a reduced set of outcome variables as secondary variables.ADAMPA 试验的主要目的是评估在基层医疗机构中，在高血压控制不足的人群中，相比于常规治疗，包含教育、SMBP 和自滴定降压药的干预措施在 12 个月内降低收缩压的效果。此外，计划进行 24 个月的被动随访延伸，
26、收集结果变量减少的组作为次要变量。Main research questions1. Does a self-management intervention based on SMBP and self-titration medication allow for better control of blood pressure?2. What is the impact of this intervention on adherence to treatments, lifestyle changes, quality of life, clinical outcomes and use o
27、f health services?3. Is this intervention cost-effective?4. What are patients , caregivers and health professionals views and experiences of SMBP plus self-titration in poorly controlled hypertension主要研究问题1. 基于 SMBP 和自滴定药物的自我管理干预能够更好地控制血压吗?2. 这种干预对治疗依从性、生活方式改变、生活质量、临床结局和医疗服务的使用有什么影响?3. 这种干预是否具有成本效益?
28、4. 在控制不良的高血压中，患者、护理人员和卫生专业人员对 SMBP 加自滴定有什么看法和经验Methods Study design and setting The ADAMPA study is a pragmatic, controlled, randomized, unblinded clinical trial with two parallel groups assigned in a ratio of 1:1 to self-management (which includes educational components, SBMP and self-titration of
29、antihypertensive medication based on a patient sGP s pre-established adjustment plan) or to usual care (with educational components too).方法 研究设计和设置ADAMPA 研究是一个务实的,控制, 随机选取临床试验和两个平行组分配比例 1:1 的自我管理(包括教育部分,SBMP 和s 基于患者的全科医生预先制定的调整计划进行降压药自滴定) 或常规治疗( 也有教育部分)。All participants belong to a Health Area in th
30、e Valencia Region (Spain), with a population coverage of 345,500 inhabitants and a geographical area covering the north-east of the city of Valencia and some surrounding towns that are served by sixteen Primary Care Centers (PCC), two Hospitals and a Medical Specialty Centre. This trial has been reg
31、istered in the https:/eudract.ema.europa.eu/ database with reference number EudraCT: 2016 003986-25.所有参与者属于瓦伦西亚地区的卫生区域(西班牙),人口为 345500 的人口覆盖率，地理区域覆盖瓦伦西亚城市的东北部和一些周边城镇，有十六个基层医疗中心(PCC),两家医院和医疗专业中心提供服务。该试验已在数据库注册 https:/eudract.ema.europa。eu/ ，编号为 EudraCT: 2016 003986-25。Study participants Identificatio
32、n and recruitmentPotential patients eligible to participate in the study will be selected by their General Practitioners (GP) among all patients attending their general practice (case-finding). In their general practice at the PCC, the GPs will inform patients of the study objective and in the case
33、that they meet the inclusion criteria and none of exclusion criteria, GPs will give them the information sheet and informed consent form, responding to all queries and concerns.研究参与者识别和招募有资格参与研究的潜在患者将由他们的全科医生(GP)在就诊的所有患者中选择(病例发现)。在基层医疗中心，如果患者符合纳入标准而没有排除标准，全科医生会告知患者研究目的，全科医生会给他们信息表和知情同意书，同时对所有的怀疑和忧虑作
34、出回应。Eligibility criteriaEligibility criteria will aim to recruit patients with treated hypertension managed in primary care, who are aged 40 years or older, have a diagnosis of hypertension in their electronic history(coded),haveameanBPreading on the reference arm of SBP 145 or diastolic blood press
35、ure (DBP) 90 mmHg on the baseline examination, who voluntarily accept participation in the study and sign the corresponding informed consent. The mean BP will be obtained as follows: In the first visit, BP should be measured on both arms. If there are differences, the reference arm should be that wi
36、th the highest value of BP. Subsequently, the average BP of at least two measurements, in the sitting position, spaced 1-2 min apart should be calculated. If the first two readings are very different, an additional measurement should be done and the mean BP will be the average of the two readings co
37、nsidered valid 8.合格的纳入标准合格的标准旨在招募在基层医疗管理且高血压在治疗的患者，40 岁以上,在电子病历诊断过高血压(编码), 基线检查时参照臂的 SBP 平均值 145 或舒张压 (DBP)的平均值 90 mmHg,自愿参与研究并签署相应的知情同意。平均血压得到的方法如下:第一次就诊时，血压需要测量双上臂。如果有差异，参考臂应该是 BP 值最高的那个。随后，至少两次坐姿血压测量的平均值，间隔 1-2 分钟计算。如果前两个读数区别不同，则需要进行额外测量，两次有效的读数的平均值即为血压平均值8。Exclusion criteria Exclusion criteria w
38、ill include inability to self-manage their BP, including dementia or significant cognitive impairment (at the discretion of the researcher performing the recruitment), a history of orthostatic hypotension (fall 20 mmHg from SBP after taking the orthostatic position), SBP 200 or DBP 100 mmHg in the b
39、aseline examination, being prescribed more than 4 antihypertensive drugs, inclusion in another hypertension study or clinical trial, presence of tremor or neurological disease that makes it difficult to perform SMBP, presence of arrhythmia, presence of terminal illness, chronic incapacitation to lea
40、ve home, an acute cardiovascular event in the last 3 months, hypertension managed directly by other specialist doctors outside the primary care environment ，pregnant women or those actively seeking to become pregnant, having a household member already enrolled in the study and non- or temporary resi
41、dents.排除标准排除标准包括,没有自己管理血压的能力的，包括痴呆或重大的认知损害(由负责招募的研究者判断), 直立性低血压病史( 立位后 SBP 下降 20 毫米汞柱),在基线检查时 SBP 200 或 DBP 100 毫米汞柱,开超过 4 种降压药,参与另外的高血压研究或临床试验,存在震颤或神经系统疾病，使得 SBPM 有困难的，存在心律失常，存在终末期疾病，长期不能离开家，在过去 3 个月发生急性心血管事件，高血压在基层医疗机构之外的由其他专科医生直接管理的。怀孕妇女或那些积极准备怀孕的，家庭成员已经登记参加研究和非或临时居民。RandomizationPatients with un
42、controlled hypertension will be randomized in a 1:1 ratio to receive either usual care or self-management using a computer randomization system via internet. Minimization will be used 24, taking into account age, gender, SBP 160 mm HG, diabetes, cardiovascular disease (ischemic heart disease, heart
43、failure, cardiomyopathy and peripheral arterial disease), stroke (chronic stroke) and chronic kidney disease status. Similar approaches have been used in previous clinical trials of self-monitoring in the control of hypertension 15, 16.随机化通过互联网使用计算机随机化系统将高血压控制不好的患者以 1:1 的比例随机化分为常规医疗或自我管理。 将使用最小化24，考
44、虑年龄、性别、SBP 160mm HG、糖尿病、心血管疾病( 缺血性心脏病、心力衰竭、心肌病和外周动脉疾病) 、中风 (慢性中风)和慢性肾病状态。在以往高血压控制的自我监测的临床试验中也使用了类似的方法15,16。Participant flow through the study 该研究参与者经过An overview of the schedule of enrolment, interventions, and assessments in the ADAMPA study, according to the SPIRIT guidelines is shown in Fig. 1. E
45、ach aspect will be described in more detail throughout the present protocol.在 ADAMPA 研究中，根据 SPIRIT 指南的注册、干预和评估的时间表概述如图 1 所示。每一个方面都将在本协议中详细描述。Recruited hypertensive patients who meet the inclusion criteria and none of the exclusion criteria, who have been duly informed (by their GP) of the characteri
46、stics of the study, have signed the informed consent and been randomly assigned to the intervention or control group, will proceed as follows招募符合纳入标准但没有排除标准的高血压患者，他们已经(由他们的家庭医生)充分被告知研究的特征，已经签署知情同意书并被随机分配到干预组或对照组，将按照如下步骤进行干预组At their practice, the GPs will have established, with each patient in the i
47、ntervention group, the BP target according to the European Guide for the management of Hypertension 2013 19 and how to act according to their BP measurements (Fig. 2), including instructions for medication self-adjustment (if necessary). At the same time, the GP will inform them that they will be re
48、called to make an appointment with a member of the research team, who will provide them with additional information about their self-management of BP and for completing data corresponding to the baseline visit.在他们的实践中，全科医生(GPs)与干预组的每个患者一起，根据 2013 年欧洲高血压管理指南19设定血压目标值和如何根据他们测量的血压采取行动(图 2)，包括药物自我调整的说明(
49、如果必要的话 )。同时，全科医生将告知他们，他们将被召回（通知）与研究小组中的那名向他们提供关于血压自我管理信息成员预约，完成与基线来访相对应的数据。Subsequently, patients will be given -and trained in the use of- a validated home blood pressure monitor (Omron M3 model HEM-7131-E), as well as the Intervention group booklet containing: the patient s code, the reference arm on which BP is measured, the BP target, general information and basic recommendations for improving BP control, instructions to manage the home blood pressure monitor, how to act according to their BP (Fig. 2)and the monthly re
