ChiCTR2400089241 版本V1.0 版本创建时间2024/09/04 11:13:28 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2400089241 

最近更新日期：

Date of Last Refreshed on：

 2024-09-04 11:13:24 

注册时间：

Date of Registration：

 2024-09-04 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

血压偏低HFrEF患者中症状引导对比血压引导治疗对预后影响的研究：开放标签研究

Public title：

A study of the comparison between symptom-guided vs. blood-pressure- guided heart failure treatment and prognosis in patients with HFrEF and low blood pressure: an open label study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

血压偏低HFrEF患者中症状引导对比血压引导治疗对预后影响的研究：开放标签研究

Scientific title：

A study of the comparison between symptom-guided vs. blood-pressure- guided heart failure treatment and prognosis in patients with HFrEF and low blood pressure: an open label study

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

李经纬 

研究负责人：

李经纬 

Applicant：

Jing-Wei Li 

Study leader：

Jing-Wei Li 

申请注册联系人电话：

Applicant telephone：

 +86 159 2289 2619

研究负责人电话：

Study leader's
telephone：

+86 159 2289 2619

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 lijingwei@tmmu.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

 lijingwei@tmmu.edu.cn

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

中国重庆市沙坪坝区新桥街道新桥医院

研究负责人通讯地址：

中国重庆市沙坪坝区新桥街道新桥医院

Applicant address：

Xinqiao Hospital, Xinqiao Street, Shapingba District, Chongqing,China

Study leader's address：

Xinqiao Hospital, Xinqiao Street, Shapingba District, Chongqing,China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

重庆市新桥医院

Applicant's institution：

Xinqiao Hospital

研究负责人所在单位：

重庆市新桥医院

Affiliation of the Leader：

Xinqiao Hospital

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 2024-研第156-02

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

中国人民解放军陆军军医大学第二附属医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of the Second Affiliated Hospital of the PLA Army Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-07-04 00:00:00

伦理委员会联系人：

胡岚岚

Contact Name of the ethic committee：

Hu Lanlan

伦理委员会联系地址：

陆军军医大学第二附属医院办公楼二楼医学伦理委员会办公室

Contact Address of the ethic committee：

Office of the Medical Ethics Committee on the Second Floor of the Office Building of the Second Affiliated Hospital of the Army Medical University

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 23 6875 5422

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

重庆市新桥医院

Primary sponsor：

Xinqiao Hospital

研究实施负责（组长）单位地址：

中国重庆市沙坪坝区新桥街道新桥医院

Primary sponsor's address：

Xinqiao Hospital, Xinqiao Street, Shapingba District, Chongqing,China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

重庆

市(区县)：

Country：

China

Province：

Chongqing

City：

单位(医院)：

新桥医院

具体地址：

中国重庆市沙坪坝区新桥街道新桥医院

Institution
hospital：

Xinqiao Hospital

Address：

Xinqiao Hospital, Xinqiao Street, Shapingba District, Chongqing,China

经费或物资来源：

新桥医院学科人才基金

Source(s) of funding：

Xinqiao Hospital Discipline Talent Fund

研究疾病：

心力衰竭  

Target disease：

heart failure

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

1. 主要目的：评估稳定性血压偏低且未使用靶剂量治疗的HFrEF患者中（未使用足够药物种类或剂量不达标），症状引导的治疗是否会降低NT-proBNP。 2. 次要目的：评估症状指导的加用药物种类/加量滴定治疗是否导致症状性低血压，改变NT-proBNP，左室射血分数，血压，心衰症状，减少死亡及心血管事件。  

Objectives of Study：

1. Main objective: To evaluate whether symptom guided treatment can reduce NT proBNP in HFrEF patients with stable low blood pressure who have not received target dose therapy (not using sufficient types of drugs or doses that are not up to standard). 2. Secondary objective: To evaluate whether the type/dosage titration therapy guided by symptoms leads to symptomatic hypotension, changes in NT proBNP, left ventricular ejection fraction, blood pressure, heart failure symptoms, and reduces mortality and cardiovascular events. Secondary Purpose: To evaluate whether symptom-guided drug addition/dose titration leads to symptomatic hypotension, changes in NT-proBNP, left ventricular ejection fraction, blood pressure, heart failure symptoms, and reduces deaths and cardiovascular events.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1）提供签署的知情同意书 2）年龄大于等于18岁 3）满足慢性症状性心力衰竭标准，诊断至少2个月： 4）纽约心脏协会（NYHA）II-IV级，左心室射血分数（LVEF）低于40%（之前1年内，最近一次，若做过心衰治疗则最近3个月） 5）根据当地检验科，NT-proBNP升高 ≥600 pg/mL(或者≥400 pg/mL如果过去12个月因心衰住院，或者 ≥900 pg/mL 如果存在房颤/房扑) 6）收缩压在85-100mmHg，若为100-110mmHg则前3月内有平均收缩压在85-100mmHg情况仍被纳入 7）无禁忌症（例如24小时内血清钾≤5.0 mEq/L (mmol/L)）和过敏，使用指南推荐的四联心衰治疗方案（ACEi/ARB/ARNi；β-blocker； MRA和sGLT2i）其中至少一种未达到靶剂量50%，剂量稳定至少4周。 8）eGFR ≥30 ml/min/1.73 m2

Inclusion criteria

1) Provide signed informed consent form 2) Age greater than or equal to 18 years old 3) Meet the criteria for chronic symptomatic heart failure and have been diagnosed for at least 2 months: 4) New York Heart Association (NYHA) grades II-IV, with a left ventricular ejection fraction (LVEF) below 40% (within the previous year, the most recent time, or within the last 3 months if heart failure treatment has been performed) 5) According to the local laboratory, NT proBNP elevation ≥ 600 pg/mL (or ≥ 400 pg/mL if hospitalized for heart failure in the past 12 months, or ≥ 900 pg/mL if atrial fibrillation/flutter is present) 6) If the systolic blood pressure is between 85-100mm Hg, and if it is between 100-110mm Hg, an average systolic blood pressure of 85-100mm Hg in the previous 3 months will still be included 7) There are no contraindications (such as serum potassium ≤ 5.0 mEq/L (mmol/L) within 24 hours) and allergies, and at least one of the recommended quadruple heart failure treatment regimens (ACEi/ARB/ARNi; β - block; MRA and sGLT2i) has not reached 50% of the target dose, and the dose has been stable for at least 4 weeks. 8) eGFR ≥30 ml/min/1.73 m2

排除标准：

1) 排除晚期心力衰竭，根据《国家心力衰竭指南2023》，定义为在优化的 GDMT、器械或外科治疗情况下，诊断必须同时满足以下标准 a) 存在严重的进行性或持续性心力衰竭症状 (NYHA 心功能分级Ⅲ级或Ⅳ级 ) b) 存在严重心脏功能障碍，满足以下至少一条标准： i. LVEF ≤ 30%； ii. 孤立性右心衰竭； iii. 存在不能手术的严重瓣膜性心脏病； iv. 存在不能手术的严重先天性心脏病； v. LVEF ≥ 40%，利钠肽水平持续升高 ( 或较前升高 )，存在严重的心脏舒张功能不全或左心室结构异常的证据 c) 过去 1 年内发生 >1 次由于下列原因引起的计划外门诊或急诊就诊或住院： i. 肺循环或体循环淤血需要高剂量静脉应用利尿剂或利尿剂联合治疗； ii. 心输出量降低导致低血压需要应用 ( 或依赖 ) 正性肌力药或血管活性药； iii. 恶性心律失常 d) 估计由心脏原因引起的活动耐量严重受损导致不能运动，或 6 分钟步行距离 <300 m，或心肺运动试验提示峰值耗氧量 <12~14 ml/(kg·min)或 <50% 预计值 2) 心源性休克 3) 器官低灌注，定义为同时满足以下4点 a) 精神状态降低 b) 四肢冰冷，网状水肿 c) 尿量<30 mL/h d) 乳酸>2 mmol/L 4) 有频繁的（一周≥ 1次）低血压症状：包括但不限于：头晕、疲劳，尤其是站立和直立时，或诊断为体位性低血压。 5) 有四联心衰药物禁忌症（例如24小时内血清钾≤5.0 mEq/L (mmol/L)）或过敏。 6) 既往滴定高剂量新四联治疗出现无法耐受（包括症状性低血压等，但不包括单纯低血压）。 7) 已知未纠正原因造成的低血压（发烧、腹泻、其他新药、脱水等） 8) 4周内因心衰住院 9) 接受静脉注射强心药（如多巴酚丁胺、米力农、左西孟丹）或静脉注射血管升压药（如肾上腺素、去甲肾上腺素、多巴胺或血管加压素） 10) 过去的90天内的心梗、不稳定型心绞痛、中风或短暂性脑缺血发作（TIA），心梗或其他心脑血管事件，心血管手术，或有明确脑血管疾病手术指征的 11) 患有严重的原发性肝(ALT或AST 大于3倍的上界，总胆红素大于2倍的上界) 12) 筛查时心电图记录静息心率>110 bpm的心房颤动或心房扑动 13) 母乳喂养、怀孕（包括预期） 14) 研究者认为可能干扰研究进行（包括结果评估）的伴随疾病、身体损伤、精神状况，或不可能完成所有方案要求的研究访视或程序，和/或遵守所有要求的研究程序。 15) 5年内的恶性肿瘤，血液系统疾病，但以下情况除外:局部皮肤基底细胞癌或鳞状细胞癌、宫颈上皮内瘤变、1期前列腺癌、乳腺导管原位癌 16) 目前正在接受另一种研究器械或药物研究的治疗，或在结束另一种试验器械或药物治疗后<30天。 17) 随机分组前30天内植入型心律转复除颤器或开始心脏再同步治疗（CRT） 18) 限制性心肌病、活动性心肌炎、缩窄性心包炎、肥厚性（梗阻性）心肌病或未纠正的原发性瓣膜病引起的心衰 19) 无起搏器的症状性心动过缓或二度或三度心脏传导阻滞 20) 心脏移植史或移植等待中，或使用或计划植入心室辅助装置。

Exclusion criteria：

1) Excluding advanced heart failure, according to the National Heart Failure Guidelines 2023, it is defined as a diagnosis that must simultaneously meet the following criteria under optimized GDMT, instrumentation, or surgical treatment a) There are severe progressive or persistent symptoms of heart failure (NYHA functional class III or IV) present b) There is severe cardiac dysfunction that meets at least one of the following criteria: i. LVEF ≤ 30%; Ii. Isolated right heart failure; Iii. There is severe valvular heart disease that cannot be surgically treated; Iv. Severe congenital heart disease that cannot be surgically treated; v. LVEF ≥ 40%, Continuous increase in levels of natriuretic peptide (or higher than before), evidence of severe diastolic dysfunction or left ventricular structural abnormalities c) More than 1 unplanned outpatient or emergency visit or hospitalization occurred within the past year due to the following reasons: i. Pulmonary or systemic congestion requires high-dose intravenous diuretics or diuretic combination therapy; Ii. Hypotension caused by decreased cardiac output requires the use (or dependence) of positive inotropic or vasoactive drugs; Iii. Malignant arrhythmia d) It is estimated that severe impairment of activity tolerance caused by cardiac reasons leads to inability to exercise, or a 6-minute walking distance of less than 300 meters, or peak oxygen consumption indicated by cardiopulmonary exercise tests of less than 12-14 ml/(kg · min) or less than 50% of the expected value 2) Cardiogenic shock 3) Organ hypoperfusion is defined as simultaneously meeting the following four criteria a) Decreased mental state b) Cold limbs, reticular edema c) Urine output<30 mL/h d) Lactic acid>2 mmol/L 4) Frequent (≥ once a week) symptoms of hypotension: including but not limited to dizziness, fatigue, especially when standing and standing upright, or diagnosed with orthostatic hypotension. 5) There are contraindications for quadruple heart failure drugs (such as serum potassium ≤ 5.0 mEq/L (mmol/L) within 24 hours) or allergies. 6) Previous high-dose new quadruple therapy with titration resulted in intolerance (including symptomatic hypotension, but not including simple hypotension). 7) Low blood pressure caused by known uncorrected reasons (fever, diarrhea, other new drugs, dehydration, etc.) 8) Hospitalization due to heart failure within 4 weeks 9) Accept intravenous injection of cardiac stimulants (such as dobutamine, milrinone, levosimendan) or intravenous injection of vasopressors (such as adrenaline, norepinephrine, dopamine, or vasopressin) 10) Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA), myocardial infarction or other cardiovascular events, cardiovascular surgery, or those with clear indications for cerebrovascular disease surgery within the past 90 days 11) Suffering from severe primary liver disease (ALT or AST greater than 3 times the upper bound, total bilirubin greater than 2 times the upper bound) 12) During screening, the electrocardiogram records atrial fibrillation or atrial flutter with a resting heart rate greater than 110 bpm 13) Breastfeeding, pregnancy (including expectations) 14) Researchers believe that comorbidities, physical injuries, mental conditions, or the inability to complete all required study visits or procedures and/or comply with all required study procedures may interfere with the conduct of the study (including outcome evaluation). 15) Malignant tumors and hematological diseases within the past 5 years, except for the following: local basal cell carcinoma or squamous cell carcinoma, cervical intraepithelial neoplasia, stage 1 prostate cancer, and ductal carcinoma in situ of the breast 16) Currently undergoing treatment with another research device or drug, or within<30 days after completion of another experimental device or drug treatment. 17) Implanted defibrillators or initiation of cardiac resynchronization therapy (CRT) within 30 days prior to randomization 18) Heart failure caused by restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or uncorrected primary valve disease 19) Symptomatic bradycardia or second or third degree heart block without a pacemaker 20) History of heart transplantation or waiting for transplantation, or using or planning to implant ventricular assist devices.

研究实施时间：

Study execute time：

从 From 2024-09-05 00:00:00至 To 2027-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-09-05 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：

实验组

样本量：

 10

Group：

Intervention Group

Sample size：

干预措施：

未使用四联治疗: 症状引导治疗组：只要没有明显低血压症状且收缩压保持在80mmHg以上，尝试逐步加药物种类至低剂量四联治疗（新加药物使用表2最低剂量，原药物不调整剂量），如果有多种药物未使用，加种类顺序采用SGLT2i→MRA→BB→RASi，依次补足未使用种类；若患者无频发低血压症状（≥2次每周），则不调低或停药。 已使用四联治疗: 症状引导治疗组：只要没有明显低血压症状且收缩压保持在80mmHg以上，根据表2的药物最低起始剂量作为滴定剂量，滴定药物，滴定优先级采用MRA→BB→RASi， 2周加量一次，尝试加量至所有药物靶剂量的50%，若某种药物初始剂量≥50%靶剂量则不调整，按序滴定其他药物种类；若患者无频发新发低血压症状（≥2次每周），则不调低或停药；

干预措施代码：

Intervention：

Not using quadruple therapy: Symptom guided treatment group: As long as there are no obvious symptoms of hypotension and the systolic blood pressure remains above 80mmHg, try gradually increasing the types of drugs to low-dose quadruple therapy (the lowest dose in Table 2 for newly added drugs, without adjusting the dose of the original drug). If multiple drugs have not been used, the order of adding drugs is SGLT2i → MRA → BB → RASi, and the unused drugs are supplemented in sequence; If the patient does not experience frequent hypotension symptoms (≥ 2 times per week), the medication should not be lowered or stopped. Four combination therapy has been used: Symptom guided treatment group: As long as there are no obvious symptoms of hypotension and the systolic blood pressure remains above 80mmHg, the lowest starting dose of the drug in Table 2 is used as the titration dose. The titration priority is MRA → BB → RASi, and the dosage is increased once every 2 weeks, trying to increase to 50% of the target dose of all drugs. If the initial dose of a certain drug is ≥ 50% of the target dose, no adjustment is made, and other drug types are titrated in sequence; If the patient does not experience frequent new symptoms of hypotension (≥ 2 times per week), the medication should not be lowered or stopped;

Intervention code：

组别：

对照组

样本量：

 10

Group：

Control Group

Sample size：

干预措施：

未使用四联治疗: 血压引导治疗组：只有收缩压>100mmHg尝试加种类至低剂量四联治疗（新加药物使用最低剂量，药物种类根据医生选择，原药物不调整剂量）。 已使用四联治疗: 血压引导治疗组：只有收缩压>100mmHg尝试加量四联治疗（根据医生选择），否则保持原治疗，除非随诊医生根据病情调整用药。

干预措施代码：

Intervention：

Not using quadruple therapy: Blood pressure guided treatment group: Only when the systolic blood pressure is greater than 100mmHg, try adding the type of medication to low-dose quadruple therapy (the lowest dose of new medication is used, the type of medication is chosen by the doctor, and the dosage of the original medication is not adjusted). Four combination therapy has been used: Blood pressure guided treatment group: Only when the systolic blood pressure is greater than 100mmHg, try to add quadruple therapy (according to the doctor's choice), otherwise maintain the original treatment, unless the attending doctor adjusts the medication according to the condition.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 重庆 

市(区县)：

  

Country：

China

Province：

Chongqing

City：

单位(医院)：

 新桥医院 

单位级别：

 三甲 

Institution
hospital：

Xinqiao Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

相对于基线，1个月内心衰标志物NT-proBNP降低30%。

指标类型：

主要指标

Outcome：

Compared to baseline, the heart failure marker NT proBNP decreased by 30% within one month.

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

相对于基线，1个月内血压左室射血分数LVEF，KCCQ-TSS的变化，症状性低血压，首次心衰恶化（心衰再入院，紧急心衰就诊）或心血管死亡事件，治疗后KCCQ-TSS改善≥10分。

指标类型：

次要指标

Outcome：

Compared to baseline, changes in left ventricular ejection fraction (LVEF), KCCQ-TSS, symptomatic hypotension, worsening of heart failure for the first time (readmission to heart failure, emergency heart failure visit), or cardiovascular death events within one month, with improvement of KCCQ-TSS by ≥ 10 points after treatment.

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

无

组织：

Sample Name：

None

Tissue：

人体标本去向

 其它  

说明

Fate of sample：

0thers  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

符合条件的受试者将以1:1的比例随机分配给强化治疗组或常规治疗组，采用中心电脑随机方案。盲法随机化将通过随机表进行。

Randomization Procedure (please state who generates the random number sequence and by what method)：

Eligible subjects will be randomized in a 1:1 ratio to either the intensive treatment group or the usual treatment group using a central computerized randomization protocol. Blinded randomization will be performed by an automated interactive network response system (IWRS).

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

单盲，研究者对结局单盲

Blinding：

Single blind, the researcher is single blind on the outcome

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

通过合理的要求可获得数据

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

Data can be obtained through reasonable requirements

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

将采用电子采集和管理系统

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Electronic Data Capture will be used.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-09-04 11:13:24