Efficacy and safety of Jia Wei Bushen Yiqi formulas as an adjunct therapy to systemic glucocorticoids on acute exacerbation of COPD: study protocol for a randomized, double-blinded, multi-center, placebo-controlled clinical trial

Abstract

Background Systemic glucocorticoids are effective for the management of chronic obstructive pulmonary disease (COPD) exacerbation but have serious adverse effects. Traditional Chinese medicine (TCM) can bring additional benefits to these patients but has few adverse effects. The present study aims to evaluate the efficacy and safety of Jia Wei Bushen Yiqi (JWBY) formulas in patients who suffer from COPD exacerbations and to investigate whether the short-term (5-days) systemic glucocorticoid therapy is non-inferior to the long-term (9-day) regime. Methods In this multi-center, randomized, double-blinded trial, eligible inpatients with COPD exacerbation are randomly assigned to four groups (A, B, C, and D). Group A will receive placebo plus 5-day prednisone, group B will receive placebo plus 9-day prednisone, group C will receive JWBY formulas plus 5-day prednisone, and group D will receive JWBY formulas plus 9-day prednisone. The primary outcomes are the time interval to the patient’s next exacerbation during a 180-day following up and the COPD assessment test (CAT) during treatment. Secondary outcomes include lung function, TCM syndrome assessment, laboratory tests, and safety. The changes of the hypothalamic pituitary adrenaline axis (HPA axis) and inflammatory cytokine will be measured as well. Discussion By demonstrating the advantages of utilizing TCM and an appropriate duration of systemic glucocorticoids, this effectiveness comparison trial will provide new references to physicians on how to improve the management of COPD exacerbation. The results of HPA axis and inflammation cytokine measurements will shed light on the molecular mechanisms and entail further mechanism studies. Trial registration www.chictr.org.cn ChiCTR1900023364. Registered on 24 May 2019.

Efficacy and safety of modified Bushen Yiqi formulas (MBYF) as an add-on to formoterol and budesonide in the management of COPD: study protocol for a multicentre, double-blind, placebo-controlled, parallel-group, randomized clinical trial: FB-MBYF Trial

“…The patients will be randomly divided into the MBYF group or the placebo group in a 1:1 ratio. Blinding will be performed as previously described [ 31 ]. Briefly, random numbers will be placed in a closed and opaque envelope without access to directly involved individuals in the study.…”

“…MBYF consists of five herbs, as shown in Table 1 [ 29 – 31 ]. Furthermore, in vivo and in vitro experiments show that MBYF and its compounds can significantly adjust inflammation and immunology [ 29 , 30 , 32 – 35 ].…”

Modified Bushen Yiqi formula attenuates neutrophils recruitment to the lung in rats model of COPD via inhibiting the CXCL1/CXCL5/CXCL8-CXCR2 axis and its downstream STAT and SRC signaling pathways

“…The rat dose of 12.5 g/kg was calculated as 9.1× human dose. The human dose of 125 g/70 kg is referenced to the clinical dose from our two clinical trials (14,19). Five herbal formulas were dissolved in ultrapure water every three days and stored at 4°C.…”

Network pharmacology prediction and molecular docking analysis reveal the mechanism of modified Bushen Yiqi formulas on chronic obstructive pulmonary disease

“…17 However, MBYF was confirmed to relieve symptoms, reduce deterioration and improve lung function for COPD patients in clinical treatment. 18,19 Network pharmacology is a new discipline based on a systems biology approach that manages large amounts of data through computation and system analysis to predict drug targets and signaling pathways. 20,21 It mainly investigates the mechanism of drug action and related pathways 21,22 and the complex interactions between biological systems, diseases, and drugs.…”

“…A study indicated that the treatment of COPD by traditional Chinese medicine (TCM) has increased significantly 17 . However, MBYF was confirmed to relieve symptoms, reduce deterioration and improve lung function for COPD patients in clinical treatment 18,19 …”