痰热清注射液联合盐酸氨溴索治疗老年退行性心脏病心力衰竭致肺部感染:随机,平行,对照,临床试验研究

Tanreqing injection combined with ambroxol hydrochloride in treating heart failure and pulmonary infection caused by senile degenerative heart disease: a parallel, randomized, controlled clinical trial

背景:老年心脏病退行性变化和机体免疫功能的降低,使老年心力衰竭患者容易受到病原菌的感染。中国传统复方中药痰热清注射液具有清热、化痰和解毒的作用,可用于治疗肺部感染。目的:试验假设采用痰热清注射液联合黏痰溶解药物盐酸氨溴索治疗老年退行性心脏病致心力衰竭伴肺部感染患者,可有效减轻肺部感染,提高心功能。方法:方案设计为前瞻性、单中心、随机、平行、对照、临床研究。纳入三亚市人民医院老年退行性心脏病心力衰竭致肺部感染患者320例,采用随机数字表法分为2组,均进行常规抗心力衰竭治疗,对照组160例(50%)加用盐酸氨溴索静脉滴注,试验组160例(50%)加用盐酸氨溴索和痰热清注射液静脉滴注,共治疗7 d。试验对象招募和资料收集时间为2019-07-01/2021-08-30,结果分析时间为2021-09-10/30,试验完成时间为2021-12-30。试验经中国海南省三亚市人民医院医学伦理委员会批准,批准号:S2015-065-03号,批准时间:2015年10月。研究符合世界医学会制定的《赫尔辛基宣言》的要求;参与者家属或本人均对试验方案和过程知情同意,并签署知情同意书。结果与结论:①研究的主要结局指标为治疗后7 d临床总有效率;②次要结局指标为治疗前、治疗后7 d左心室收缩末内径、左心室舒张末内径、左心室射血分数、左心室短轴缩短率、肺部感染病原菌数量、血清中降钙素原及C-反应蛋白水平变化;治疗后7d不良反应发生率;③课题组于前期(2016年5月至2017年10月)已完成了老年心力衰竭患者120例小样本试验,随机分为试验组和对照组各60例,均占50%,结果发现,老年心力衰竭患者肺部感染病原菌以革兰阳性菌为主,对照组和试验组均为53.7%,治疗后试验组患者的病原菌数目明显低于对照组患者病原菌的数目(对照组:试验组=17株:11株);与治疗前相比,试验组和对照组患者治疗后左心室收缩末内径,左心室舒张末内径及左心室射血分数均明显降低(P <0.05),而左心室短轴缩短率水平明显升高(P <0.05),血清降钙素原及C-反应蛋白水平均明显降低(P <0.05),且试验组上述指标变化更显著(P <0.05);④试验希望证实,痰热清注射液联合盐酸氨溴索可明显改善老年心力衰竭患者的心功能,并能明显减轻病原菌致肺部感染,在此明确由于心脏病退行性改变而发生的特征性药物不良反应。试验已在中国临床试验注册中心注册(注册号:ChiCTR1900022879),注册时间:2019-04-29,方案版本号1.0,注册成功后开始纳入患者,研究成果科在国内外相关会议报告,可在国内外相关开放获取杂志发表。

BACKGROUND: The degenerative changes of heart disease in the elderly and the decrease of immune function of the body make the elderly patients with heart failure vulnerable to the infection of pathogenic bacteria. Tanreqing injection, a traditional Chinese compound medicine, has the functions of clearing heat, eliminating phlegm and detoxifying, and can be used to treat pulmonary infection.OBJECTIVE: To hypothesize that Tanreqing injection combined with ambroxol hydrochloride, a mucolytic drug, can effectively alleviate pulmonary infection and improve cardiac function in elderly patients with heart failure and pulmonary infection caused by degenerative heart disease.METHODS: This prospective, single-center, parallel, randomized, controlled clinical trial will include 320 patients with heart failure combined with pulmonary infection induced by senile degenerative heart disease from Sanya People’s Hospital, Sanya, China. All patients will receive conventional anti-heart failure treatment, and will be equally and randomly divided into a control group and a trial group. The patients in the control group will be treated with intravenous infusion of ambroxol hydrochloride. The patients in the trial group will be treated with intravenous infusion of ambroxol hydrochloride and Tanreqing injection. The treatment will be lasted for 7 days. Patient recruitment and data collection will begin on July 1, 2019 and end on August 30, 2021. Analysis of the results will be performed from September 10 to 30, 2021. This study will be scheduled to end on December 30, 2021. This study was approved by the Medical Ethics Committee of Sanya People’s Hospital in October2015(approval No. S2015-065-03). This study will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Written informed consent regarding the study protocol and surgery procedure will be obtained from the participants’ family members or the participants themselves.RESULTS AND CONCLUSION:(1) The primary outcome measure is total effective rate 7 days after treatment.(2) The secondary outcome measures are left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, left ventricular fractional shortening, number of pathogenic bacteria in the lung, serum procalcitonin and C-reactive protein level changes before and 7 days after treatment, as well as incidence of adverse reactions 7 days after treatment.(3) Our pilot study involved 120 patients with senile heart failure from May 2016 to October 2017. These patients were randomly assigned to trial and control groups(n=60 per group). The results showed that Gram-positive bacteria were the main pathogens of pulmonary infection in senile patients with heart failure. The positive rate of Gram-positive bacteria was 53.7% in both control and trial groups. After treatment, the number of pathogenic bacteria in the trial group was remarkably lower than that in the control group(control group: trial group=17 strains: 11 strains). Compared with that before treatment, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and left ventricular ejection fraction were significantly lower(P < 0.05),but left ventricular fractional shortening was significantly higher(P < 0.05), and serum procalcitonin and C-reactive protein levels were significantly decreased(P < 0.05) in both trial and control groups after treatment. Moreover, the changes of the above indicators were more significant in the trial group than in the control group(P < 0.05).(4) The results of the present study will confirm that Tanreqing injection combined with ambroxol hydrochloride can noticeably improve the cardiac function of senile patients with heart failure, and can obviously mitigate pulmonary infection caused by pathogenic bacteria. This study will identify adverse drug reactions due to degenerative heart disease.This study was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR1900022879) on April 29, 2019. Protocol version: 1.0. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal.