Tanreqing injection with ambroxol hydrochloride for heart failure and pulmonary infection in senile degenerative heart disease: a randomized controlled trial

Abstract

Background and objective: Degenerative changes in the heart with age and decreased immune function mean that older adult patients with heart failure are vulnerable to infection by 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. We hypothesized that Tanreqing injection combined with ambroxol hydrochloride, a mucolytic drug, may effectively alleviate pulmonary infection and improve cardiac function in older adult patients with heart failure and pulmonary infection caused by degenerative heart disease. Participants and methods: This prospective, single-center, 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. Patients in both groups will be treated with intravenous infusion of ambroxol hydrochloride, while patients in the trial group will additional receive Tanreqing injection. The treatment period will be 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 10–30, 2021. This study is scheduled to end on December 30, 2021. The study protocol was approved by the Medical Ethics Committee of Sanya People’s Hospital in October 2015 (approval No. S2015-065-03). Study protocol version is 1.0. This study will be performed in accordance with the principles of the Declaration of Helsinki. Written informed consent to participate will be obtained from participants or their family members. Results: The primary outcome measure is total effective rate after 7 days of treatment. Secondary outcome measures are change from baseline in 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 level, and C-reactive protein level after 7 days of treatment, as well as incidence of adverse reactions after 7 days of treatment. In a pilot study among 120 patients with senile heart failure conducted from May 2016 to October 2017, patients were randomly assigned to trial and control groups (n = 60 per group). Gram-positive bacteria were found to be the main pathogens responsible for pulmonary infection in senile patients with heart failure, with a positive rate of 53.7% in both control and trial groups. After treatment, the number of pathogenic bacteria in the trial group was markedly lower than that in the control group (11 strains versus 17 strains). Furthermore, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular ejection fraction were significantly lower (P < 0.05) after treatment, but left ventricular fractional shortening was significantly higher (P < 0.05). Serum procalcitonin and C-reactive protein levels were significantly decreased (P < 0.05) in both groups after treatment, although the changes were more significant in the trial group compared with the control group (P < 0.05). Conclusion: The results of this planned study will confirm whether Tanreqing injection combined with ambroxol hydrochloride can markedly improve cardiac function in senile patients with heart failure and mitigate pulmonary infection caused by pathogenic bacteria. This study will also identify adverse drug reactions associated with the study treatment. Trial registration: This study was registered with the Chinese Clinical Trial Registry on April 29, 2019 (registration number: ChiCTR1900022879).