Efficacy and safety of Xuebijing injection for radiation pneumonitis: A meta-analysis

Background Currently, the treatment of radiation pneumonitis (RP) remains a clinical challenge. Although glucocorticoids are used for RP treatment, they have associated side effects. Xuebijing injection (XBJ) has been widely used for RP treatment in China, but so far no meta-analysis has evaluated its efficacy and safety. Methods PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure, WANFANG database, SinoMED, and China Science and Technology J Database were searched for randomized controlled trials related to XBJ in RP treatment. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment. The outcomes were synthesized and analyzed using the Cochrane Review Manager (RevMan 5.3) software, and a forest plot generated. Result Eight articles met the eligibility criteria for further data extraction and meta-analysis. A total of 578 patients with RP participated in these studies, including 296 in the experimental group (XBJ+BT), and 282 in the control group (BT). The results of the meta-analysis revealed that compared to the BT group, XBJ+BT significantly increased the total effective rate (n = 578; RR = 1.45, 95% CI: 1.30 to 1.61, p<0.0001), and IL-10 expression (n = 296; MD = 17.62, 95% CI:13.95 to 21.29, p<0.00001), decreased interleukin-6 (IL-6) expression (n = 296; MD = -21.56, 95% CI:-27.37 to -15.76, p<0.00001), that of tumor necrosis factor alpha (n = 246; MD = -25.63, 95% CI:-30.77 to -20.50, p<0.00001), and that of C-reactive protein (n = 296; MD = -48.61, 95% CI:-56.49–40.73, p< 0.00001). Conclusion Based on our results, we do not recommend XBJ as an adjuvant treatment for RP. Further randomized controlled trials with rigorous design, strict implementation, and standard reporting are needed to further evaluate the efficacy and safety of XBJ for RP treatment. Systematic review registration INPLASY registration number: INPLASY2020120037.

Condition being studied: At present, the treatment of Radiation Pneumonitis (RP) is still a clinical problem. Although a variety of drugs such as glucocorticoids and antibiotics are used for RP treatment, side effects remain to be inevitable. Xuebijing injection(XBJ), a Chinese herbal injection , has been widely used in Radiation Pneumonitis treatment, but there is no published systematic review to evaluate its efficacy and safety.

C o m p a r a t o r : G l u c o c o r t i c o i d s , bronchodilators, antibiotics, oxygen therapy and respiratory support treatment lucocorticoids, bronchodilators, antibiotics, oxygen therapy and respiratory support treatment if necessary.
Study designs to be included: Only RCTs will be eligible for inclusion regardless of the languages. It will not include animal experiments, case reports, non-clinical researches, commentaries, repeated publications, etc. RCTs with incomplete and unavailable important data will not be included.
Eligibility criteria: 1. Types of studies. Only RCTs will be eligible for inclusion regardless of the languages. It will not include animal experiments, case reports, non-clinical researches, commentaries, repeated publications, etc. RCTs with incomplete and unavailable important data will be excluded. 2. Type of participants. The study will recruit participants over 18 years of age who met the histological or pathological or clinical diagnostic criteria for Radiation Pneumonitis. There will be no restrictions on gender, nationality, race, education and job. 3. Type of interventions. The interventions will contain two groups: experimental group and control group.

The interventions of control group will include g l u c o c o r t i c o i d s , b r o n c h o d i l a t o r s , antibiotics, oxygen therapy and respiratory support treatment if necessary. The interventions of experimental group will include the interventions of control group
and Xuebijing injection. 4. Primary outcomes. The primary outcome is the total effective rate. In brief, the total effective rate equals the cure rate and the effective rate. 5. Secondary outcomes. The secondary outcome will consist of inflammation-related indicators such as Creactive protein , tumor necrosis factor alpha, interleukin-6, interleukin-10, etc. and adverse events.

I n f o r m a t i o n s o u r c e s : W e w i l l comprehensively search 7 databases: PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), WANFANG database, SinoMED and China Science and Technology Journal Database (VIP).
There is no limitation of the language.The time interval for literature searching will be from inception of the library to October 1, 2020.

Quality assessment / Risk of bias analysis: Two reviewers will use the "risk of bias a s s e s s m e n t t o o l " o f t h e C o c h r a n e
Handbook to evaluate the risk of bias of the included RCTs. The evaluation criteria include the method of random sequence generation, allocation concealment, blinding of patients, personnel and assessors, incomplete outcome data, selective reporting, and other sources of bias. Any disagreement will be resolved by the third reviewer.
Strategy of data synthesis: Data synthesis and analysis will be conducted by Revman 5.3 software. Different data types will be processed in different ways: continuous data and dichotomous data will be evaluated by standard mean difference (SMD) with 95% confidence interval (95% CI) and rate ratio (RR) with 95% CI respectively. The heterogeneity will judged by the I² value. For I²50%, the fixed effects model and the random effects model will be used respectively. Subgroup analysis: We will conduct subgroup analysis based on interventions, participants characteristics, and outcome measurement if the included articles are at least 10. Sensibility analysis: In the sensitivity analysis, we will remove each study in turn to observe the impact on the overall results.

K e y w o r d s : R a d i a t i o n P n e u m o n i t i s , Xuebijing injection, Efficacy and safety, Randomized controlled trials, Metaanalysis.
Contributions of each author: Author 1 -Zheng Li wrote the protocol and revised the manuscript. Email: lizheng_gam@163.com Author 2 -Dandan Wang wrote the protocol and revised the manuscript. Email: wdd19940416@163.com Author 3 -Shuo Wang developed the criteria and conducted statistical methods. Email: 18701522023@163.com