Abstract
Background
Florensocatib (formerly known as HSK31858) is a novel reversible inhibitor of dipeptidyl peptidase 1. We sought to determine the efficacy and safety of florensocatib in decreasing exacerbation frequency in Chinese adults with bronchiectasis.
Methods
The HOPE-BE trial was a phase 3, randomised, placebo-controlled trial which determines the efficacy and safety of high-dose florensocatib (40 mg once daily) versus placebo in Chinese adults with bronchiectasis who had two or more exacerbations within the past year. Patients were randomly assigned in a 2:1 ratio to receive florensocatib 40 mg or matching placebo once daily for 52 weeks. We recorded demographics, medical history, bacterial infection status and quality-of-life and performed spirometry at baseline.
Results
We randomised 700 patients who were enrolled from 67 sites in mainland China between September 2024 and November 2025. 60.4% of patients were female. 559 (79.9%) and 141 (20.1%) of patients, respectively, had two and three or more exacerbations in the past year. The median (interquartile range) of 24-h sputum weight was 14.8 (29.3) g, and the median (interquartile range) of sputum purulence score was 5.0 (2.0). 192 (27.4%) patients were culture positive to Pseudomonas aeruginosa, and demonstrated significantly higher 24-h sputum volume and purulence score, and lower lung function and quality-of-life scores. Significant geographical variations were seen regarding comorbidity, blood eosinophil counts and sputum bacteriology.
Conclusion
The baseline demographic characteristics of the HOPE-BE trial may provide important clues to future therapeutic efficacy assessment in adults with bronchiectasis.
Shareable abstract
The HOPE-BE trial seeks to determine the efficacy and safety of high-dose florensocatib in bronchiectasis https://bit.ly/4sErj3S
Introduction
Bronchiectasis is a common chronic respiratory disease in which neutrophilic inflammation is responsible for chronic sputum production and frequent exacerbations [1–3]. Clinical practice guidelines have highlighted the paucity of licensed therapy [4–7]. Although low-dose macrolides significantly decrease symptom burden and exacerbation risks [8], long-term administration increased the risks of resistance and diminished therapeutic responses [9, 10]. The guidelines have addressed the unmet needs in developing new drugs to halt disease progression via mitigating airway inflammation [4–7].
Despite the heterogeneity in clinical manifestations, activated neutrophils may release neutrophil serine proteases (NSPs) such as neutrophil elastase, cathepsin G and proteinase 3 [11, 12]. Bronchiectasis patients with higher levels of sputum matrix metalloproteinase and neutrophil elastase exhibited significantly elevated risk of exacerbations [3, 13]. The activated inflammasome within airway epithelium and neutrophils potently induced neutrophil extracellular traps formation that damage airways [14]. Hence, targeted therapies might translate into clinical benefits.
Dipeptidyl peptidase-1 (DPP-1, cathepsin C) is the upstream switch controlling NSP synthesis within neutrophils. Interventions that inhibit DPP-1 may maintain neutrophil effector functions while minimising NSP release [11, 15, 16]. Several small molecules could effectively suppress DPP-1 activity. Brensocatib significantly decreased exacerbation frequency, prolonged the time to the first exacerbation and markedly decreased sputum NSP concentrations in the WILLOW [17] and ASPEN trial [18], while BI 1291583 demonstrated a significant dose–response benefit and nominally lowered the exacerbation risk in the AIRLEAF trial [19]. Both drugs were well tolerated.
Expanding the list of DPP-1 inhibitors may consolidate the evidence of targeted therapies of neutrophilic inflammation and improve drug accessibility globally. Florensocatib (HSK31858) is a novel oral reversible DPP-1 inhibitor with high potency in inhibiting NSP activity in vitro. Following safety assessment in two phase 1 trials [20], the SAVE-BE trial demonstrated a 60% reduction in exacerbation risk, markedly decreased daily sputum weight and a high safety profile among Chinese adults with bronchiectasis [21].
We conducted the phase 3 trial of florensocatib among Chinese adults with bronchiectasis (ClinicalTrials.gov registry: NCT06660992). The primary goal is to assess the effects of florensocatib in decreasing the annualised exacerbation frequency of bronchiectasis over 52 weeks. Secondary objectives included the assessment of florensocatib in prolonging the time to the first exacerbation, decreasing sputum volume and purulence, improving lung function and quality-of-life, etc.
Here, we report the design of the HOPE-BE trial and outline baseline demographic characteristics.
Methods
Study design and end-points
HOPE-BE is a phase 3, randomised, placebo-controlled trial which determined the efficacy and safety of high-dose florensocatib (40 mg once daily) versus placebo in Chinese adults. Eligible participants were randomly assigned 2:1 to receive florensocatib 40 mg (treatment group) or matching placebo (placebo group) once daily for 52 weeks, followed up for safety for 4 weeks thereafter. Study visits occurred at baseline, day 1 and weeks 4, 16, 28, 40 and 52 and at four sessions via telephone (weeks 10, 22, 34 and 46).
The primary efficacy end-point was the annualised frequency of exacerbation within 52 weeks compared with placebo. We defined an acute exacerbation based on the EMBARC expert consensus as the new onset or deterioration of three or more symptoms lasting for >48 h that resulted in antibiotic treatment [22]. Severe exacerbations denoted those requiring hospitalisation.
Secondary efficacy end-points consisted of the time to the first exacerbation, the proportion of patients without exacerbation within 52 weeks, the change from baseline in forced expiratory volume in 1 s (FEV1) at 52 weeks, change from baseline in 24-h sputum weight at 52 weeks, change from baseline in sputum purulence score at 52 weeks, and the change from baseline to week 52 in the Respiratory Symptoms Scale of the Quality of Life Questionnaire for Bronchiectasis (QoL-B-RSS) [23]. The exploratory end-point was the change from baseline in the Bronchiectasis Health Questionnaire (BHQ) score at 52 weeks [24].
Study participants
Key inclusion criteria
We enrolled adult outpatients from 67 sites in mainland China between September 2024 and November 2025 (supplementary table S1). Eligible patients were aged ≥18 years, had a body mass index of ≥18.0 kg·m−2, had a clinical diagnosis of bronchiectasis affecting one or more lung lobes based on chest computed tomography (bronchial dilatation and compatible respiratory symptoms), and had two or more documented exacerbations within the 12 months before screening.
The trial was conducted by following the Declaration of Helsinki and the Good Clinical Practice. The trial protocol has been approved by The First Affiliated Hospital of Guangzhou Medical University and each participating site.
Core exclusion criteria
Core exclusion criteria included a primary diagnosis of COPD or asthma, cystic fibrosis, destroyed lungs, and active mycobacterial or fungal disease necessitating active treatments. Other important exclusion criteria were severe systemic diseases (e.g. uncontrolled hypertension or diabetes, recent stroke), active hepatitis, malignancy within last 5 years, exacerbation within last 4 weeks, antibiotic use (except for low-dose macrolides) within last 4 weeks, pregnancy or lactation. See the supplementary appendix for details.
Randomisation and masking
We randomly assigned eligible patients who had completed the 4-week screening via a central interactive Web-response system. Because in the phase 2 SAVE-BE trial, the 40 mg doses yielded a greater reduction than the 20 mg doses in exacerbation frequency (60% versus 48% reduction) and a similar safety profile [21], the investigators had reached consensus with the National Medical Products Administration that only the 40 mg doses be retained. Randomisation was stratified by the exacerbation frequency within the previous year (<3 versus ≥3 annually). The sequence of allocation was concealed by the electronic case report form system. Both study investigators and participants were masked.
Study procedures
Assessments at screening consisted of the documentation of demographics, medical history and exacerbations, previous and concomitant medications. Participants were requested to complete a chest computed tomography (waved if the participant had undergone one within 12 months at the same site). All chest radiographs were transferred to the leading site, where two senior independent radiologists who remained blinded throughout the trial provided central review. Spontaneous sputum was collected at screening, throughout treatment visits and at follow-up visits, and could be aided by chest physiotherapy – postural drainage and active cycle of breathing. However, induction was allowed when spontaneous sputum could not be provided despite multiple attempts. Fresh sputum was sent to the microbiology laboratory for conventional culture. Spirometry was performed with the core metrics of forced vital capacity, FEV1 and maximal mid-expiratory flow. Patients at baseline completed the QoL-B-RSS (to calculate the QoL-B-RSS, range: 0–100, with higher scores indicating better quality of life) [23] and the BHQ (to calculate the total score, range: 0–100, with higher scores indicating better quality of life) [24].
Participants collected 24-h sputum in the designated transparent sterile plastic pots, submitted the next day following screening to determine baseline daily sputum weight and purulence. All 24-h sputum pots were weighted on an electronic balance. Sputum purulence was rated based on the standardised colour chart.
Adherence and adverse events recording
Adherence was defined as the percentage of the number of study drugs consumed over the entire number of study drugs dispensed during treatment. We rated adherence as good if participants had administered 80% to 120% of the intended quantity of florensocatib or placebo (tablet counting conducted upon follow-up).
We evaluated safety profiles throughout week 52 by documenting the adverse events (AEs), conducting physical examinations, laboratory testing and 12-lead electrocardiography. Investigators documented the AEs via meticulous questions, physical examination and diary card inspection.
Sample size estimation
Based on the WILLOW and SAVE-BE trial [17, 21], we assumed an annualised exacerbation rate of 1.37 events per patient-year in the placebo group and 0.87 events per patient-year in the florensocatib group, based on the negative binomial dispersion settings. We fitted a negative binomial distribution model by using the exacerbation frequency data from the SAVE-BE trial [21], where the estimated dispersion parameter was 1.27 (95% confidence interval (95% CI) 0.81–1.99). We estimated the enrolment of 446 patients in the florensocatib group and 223 in the placebo group (totaling 669 patients) with a one-sided significance level of 0.025, a power of 90%, a negative-binomial dispersion parameter of 1.40 and a 20% dropout rate.
Statistical analysis
The full analysis set (FAS) was the principal analysis set, while the per-protocol set (PPS) was the supportive set. For the primary end-point, we adopted the negative binomial model, with the incidence rate ratio and the corresponding 95% CI being demonstrated, to analyse the annualised exacerbation frequency up to 52 weeks. This model assumed that for participants who discontinued prematurely, the annualised exacerbation rate from discontinuation to Week 52 would be identical to the rate observed from randomisation to discontinuation. To assess the impact of deviation from this assumption, sensitivity analysis was performed under a missing-not-at-random framework. The number of exacerbations occurring between premature discontinuation and week 52 was multiply inputed by using Copy Reference and Tipping-Points Analysis. We compared the two groups by using the Andersen–Gill intensity model. In the PPS, the same negative binomial model was employed as in the primary analysis. All intercurrent events were handled with the while-on-treatment strategy, analysed identically to the primary analysis. Concomitant use of other drugs sharing the same therapeutic target was addressed with the treatment policy strategy, while all other aspects remain unchanged and were analysed as in the primary analysis. Deaths from any cause was consistently handled with the composite strategy, with all other aspects unchanged and analysed using the same approach as the primary analysis.
For secondary end-points, the time to the first exacerbation was summarised with Kaplan–Meier curves; the two groups were compared with the log-rank test and by restricted mean survival time model. A Cox regression model was used to estimate the hazard ratio for the time to the first exacerbation. The proportion of patients who remained free of exacerbations was compared with a logistic regression model that included the number of exacerbations in the previous 12 months (<3 versus ≥3) as covariate. Changes from baseline in FEV1, 24-h sputum weight, sputum purulence score and QoL-B-RSS at Week 52 were analysed with the mixed model for repeated measures (MMRM). This included the baseline value of the secondary end-point and the number of exacerbations in the previous year (<3 versus ≥3) as the covariate, and treatment group, visit and the treatment-by-visit interaction as fixed effects. Least-squares mean differences between two groups and 95% CIs were calculated.
Subgroup analyses of the primary end-point was performed in the FAS according to the baseline: 1) Pseudomonas aeruginosa infection (present versus absent); and 2) long-term macrolides therapy (yes versus no). The same method used in the primary analysis of the primary end-point was applied.
The Safety Set served as the safety analysis population. Safety data were summarised according to the treatment actually received and evaluated regarding the incidence and severity of AEs. All AEs were coded using MedDRA version 27.0 or higher and graded according to CTCAE version 5.0. The incidence of treatment-emergent adverse events were summarised by System Organ Class and Preferred Term, and further classified within each category by the type of suspected relationship to the study drug and by severity.
For pharmacokinetic analysis, blood concentrations collected at the scheduled sampling visits were summarised descriptively for all dosed individuals. For exploratory analysis, the change in BHQ score from baseline to Week 52 was analysed using the MMRM.
All analyses were presented with two-sided p-values at a significance threshold of 0.05. We did not input any missing data. We applied no hierarchical order for evaluating secondary end-points and no adjustment for multiplicity.
Results
Patients
Of 885 patients who underwent screening, 702 underwent randomisation. Two patients failed to produce sufficient spontaneous sputum for bacterial culture and were not included in the FAS. Therefore, 700 patients were retained in the FAS. Figure 1 demonstrates the study design and the main inclusion/exclusion criteria.
FIGURE 1.
Study design flow chart. EoS: end of study; QoL-B: Quality of Life Bronchiectasis; CF: cystic fibrosis; NCFBE: non-cystic fibrosis bronchiectasis; FEV1: forced expiratory volume in 1 s.
Demographic characteristics
Baseline demographic characteristics are presented in table 1. The mean age was 55.7 years, and 60.4% of patients were female. The median (interquartile range) of 24-h sputum weight was 14.8 (29.3) g, and that of sputum purulence score was 5.0 (2.0). 85.1% of patients were never-smokers. The mean±sd of QoL-B-RSS was 66.0±16.5 points. 559 (79.9%) of patients had two and 141 (20.1%) had three or more documented exacerbations in the previous year.
TABLE 1.
Baseline demographic characteristics, past history, comorbidities and concomitant use of medications in patients (n=700)
| Age years, mean±sd | 55.7±12.3 |
| Female sex, n (%) | 423 (60.4%) |
| Body mass index, kg·m−2, mean±sd | 22.4±3.4 |
| 24-h sputum weight, g, median (IQR) | 14.8 (29.3) |
| Sputum purulence score, median (IQR) | 5 (2) |
| QoL-B-RSS, mean±sd | 66.0±16.5 |
| Never-smokers, n (%) | 596 (85.1%) |
| Exacerbations in the previous year, n (%) | |
| 2 exacerbations | 559 (79.9%) |
| ≥3 exacerbations | 141 (20.1%) |
| Respiratory diseases, n (%) | |
| Asthma | 63 (9.0%) |
| COPD | 219 (31.3%) |
| Systemic comorbid diseases, n (%) | |
| Cardiovascular | 198 (28.3%) |
| Gastrointestinal | 250 (35.7%) |
| Hepatic | 0 (0%) |
| Metabolic | 285 (40.7%) |
| Depression | 9 (1.3%) |
| Anxiety | 19 (2.7%) |
| Cerebrovascular | 211 (30.1%) |
| Renal | 131 (18.7%) |
| Concomitant use of medications, n (%) | |
| Inhaled corticosteroids | 58 (8.3%) |
| Long-acting β2-agonist | 103 (14.7%) |
| Long-acting muscarinic receptor antagonist | 100 (14.3%) |
| Mucoactive drugs | 83 (11.9%) |
| Maintenance low-dose macrolides | 14 (2.0%) |
IQR: interquartile range; QoL-B-RSS: Quality-of-life-Bronchiectasis Respiratory Symptom Score.
63 (9.0%) patients had coexisting asthma and 219 (31.3%) had coexisting COPD. When stratified by geographical region, the proportions of respiratory diseases were highest in central China and lowest in south China (figure 2). When analysing other systemic diseases, metabolic disorders ranked first (n=285, 40.7%), followed by gastrointestinal disorders (n=250, 35.7%) and cardiovascular disorders (n=211, 30.1%). The use of concomitant medications varied considerably across different regions, particularly for mucoactive drugs and inhaled bronchodilators (figure 3).
FIGURE 2.
Coexisting chronic respiratory diseases among study participants and stratified analyses. a) Baseline chronic respiratory diseases of study participants. (b) The proportion of patients with chronic respiratory diseases across different geographical regions of mainland China.
FIGURE 3.
The proportion of patients with major categories of concomitant medications across different geographical regions of mainland China.
Regarding concomitant use of medications, the most common type was long-acting bronchodilators (∼15%), followed by mucoactive drugs (11.9%). 8.3% of patients reported the use of inhaled corticosteroids, and low-dose macrolides was used in 2.0% of patients only.
Functional and laboratory testing
The mean±sd pre-bronchodilator FEV1 was 69.6±24.3% predicted. 38.9% of patients had an FEV1 of 80% predicted or higher, and this was 35.1% for FEV1 between 50% and 80% predicted, and 21.7% for FEV1 between 35% and 49% predicted. 68 (9.7%) patients had a blood eosinophil count of ≥300 cells·μL−1, with minor geographic differences in the proportion of patients with blood eosinophilia (figure 4). P. aeruginosa was isolated from 192 (27.4%) patients (table 2).
FIGURE 4.
The proportion of patients with blood eosinophilia across different geographical regions of mainland China.
TABLE 2.
Baseline functional and laboratory test findings in patients (n=700)
| Lung function, mean±sd | |
| FEV1, L | 1.78±0.76 |
| FEV1 % predicted | 69.6±24.3 |
| FEV1 category, n (%) | |
| >80% | 272 (38.9%) |
| 50–80% | 246 (35.1%) |
| 35–49% | 152 (21.7%) |
| <35% | 30 (4.3%) |
| Blood eosinophil count category, n (%) | |
| <300 cells·μL−1 | 632 (90.3%) |
| ≥300 cells·μL−1 | 68 (9.7%) |
| Pseudomonas aeruginosa isolated, n (%) | |
| Yes | 192 (27.4%) |
| No | 508 (72.6%) |
FEV1: forced expiratory volume in 1 s.
Patient characteristics stratified by P. aeruginosa isolation
Patients isolated with P. aeruginosa demonstrated a significantly higher 24-h sputum volume (median: 23.6 versus 12.1 g) and sputum purulence score (median: 6 versus 4) than those without. The proportion of patients who had three or more exacerbations within the previous year was markedly higher in patients with isolation of P. aeruginosa than those without (26.0% versus 18.0%). Both the QoL-B-RSS (mean: 60.6 versus 68.0 points, p<0.05) and FEV1 (mean: 61.3% versus 72.8%, p<0.05) was significantly lower in patients with P. aeruginosa isolation than those without. However, the percentage of patients with blood eosinophilia did not differ significantly, nor did the concomitant use of inhaled corticosteroids or low-dose macrolides (figure 5a). Patients residing in south China yielded the highest rate of P. aeruginosa positive culture (37.9%), followed by patients living in north China (32.1%). By contrast, the lowest rate of P. aeruginosa isolation was identified among patients residing in east China (23.5%) (figure 5b).
FIGURE 5.
Baseline clinical characteristics stratified by sputum culture status of Pseudomonas aeruginosa. a) Baseline clinical characteristics of study participants with or without P. aeruginosa isolated at baseline. b) The proportion of patients with positive culture findings of P. aeruginosa across different geographical regions of mainland China. IQR: interquartile range; QoL-B-RSS: Quality-of-life-Bronchiectasis Respiratory Symptom Score; FEV1: forced expiratory volume in 1 s.
Discussion
The study design and baseline demographic characteristics for the HOPE-BE trial are reported here. Our findings for patient demographic characteristics echoed those in the SAVE-BE trial [21] regarding the mean age (56 versus 56 years), percentage of female patients (60% versus 61%) and never-smokers (85% versus 86%), percentage of patients with coexisting asthma (9% versus 8.5%) and COPD (31% versus 26%), and percentage of patients with three or more exacerbations in the past year (20% versus 21%). Compared with the AIRLEAF [19], WILLOW [17] and ASPEN trials [18], our cohort was younger and had a higher proportion of never-smokers and fewer annual exacerbations.
Two important treatable traits, the 24-h sputum weight and sputum purulence score, cannot be compared because they were not reported in three other trials [17–19]. As with the SAVE-BE trial [21], the therapeutic effects of florensocatib in improving respiratory symptoms in terms of decreasing 24-h sputum weight and sputum purulence score will be explored with a larger sample size in the HOPE-BE trial.
Sputum bacteriology is an important determinant of the clinical outcomes of bronchiectasis, and the primary end-point and key secondary end-points will be analysed by stratifying the isolation status of P. aeruginosa in the HOPE-BE trial. In the next stage of data analysis, comparison of the disease severity will be possible following the incorporation of the BSI metric when the trial is formally completed.
The HOPE-BE trial adopted the higher dose group of florensocatib only. Because of the reasons mentioned in the Methods, the principal investigators concurred with the National Medical Products Administration that patients should be randomised in a 2:1 ratio to maximise the probability of receiving the optimal treatment.
The HOPE-BE trial also determined the efficacy of florensocatib in decreasing the 24-h sputum weight and sputum purulence score, because the aggravated neutrophilic inflammation elicited mucus hypersecretion. Decreased daily sputum weight was indicative of mitigated airway inflammation and improved quality of life. Our findings would provide further evidence on top of the clinical trial of florensocatib in adults with airway mucus hypersecretion (Clinicaltrials.gov registry: NCT06820749).
Our study is limited by the demonstration of baseline characteristics. Currently, acquisition of chest computed tomographic images is ongoing, and rating of the modified Reiff score by two independent senior radiologists and calculation of the Bronchiectasis Severity Index, along with other important information such as the underlying etiology and the CONSORT diagram (because our study has not been unblinded), will be reported in a future publication. Furthermore, there existed some differences in patient characteristics such as concomitant use of low-dose macrolides or inhaled antibiotics (patients have rarely received regular treatments prior to inclusion in our trial). Future studies will continue to explore, with a number of simple clinical metrics, the bedside tools to predict the efficacy of florensocatib.
The marketing approval of brensocatib has signalled the triumph of targeted anti-inflammatory drugs for bronchiectasis. The HOPE-BE trial is the largest randomised controlled trial of a DPP-1 inhibitor in the Chinese population. It could help to decipher the possible differences in therapeutic response to different DPP-1 inhibitors across different study populations. Full trial results will be published in future publications.
Acknowledgments
We are grateful to the continuous support from Pang-ke Yan, Xing-xing Yan, Meng-lin Fan, Xia-fei Lv, Ye-yun Li, Li-li Lan and Xin-chan Luo (Haisco Co. Ltd, Sichuan, China) in facilitating the study conduct. We thank Jin-fang Ma, Xiao-xian Zhang, Xin-yun Yang, Hui-min Li and Zhi-min Zhou (The First Affiliated Hospital of Guangzhou Medical University) for their efforts in recruiting patients and performing follow-up visits and laboratory testing. We also thank all study participants for their support to complete the study. Finally, we thank Scientific Research Center of Guangzhou Medical University for providing instrument analysis and measurement.
Footnotes
Provenance: Submitted article, peer reviewed.
HOPE-BE study group: Nan-shan Zhong, Wei-jie Guan, Jie Cao, Yan Feng, Xun-chao Liu, Guo-jun Zhang, Huan Ye, Zhi-jun Liang, Hui Shen, Zhang Bao, Zhi-ren Yang, Ling-feng Min, Hui Jiang, Rong Qiu, Jian-ping Liang, Jin-li Liu, Li-min Dong, Xin-yu Song, Jin-xiang Wang, Yan-ming Huang, Fang-qiong Li, Lu-yin Sun, Han-mo Liu, Na Huang (The First Affiliated Hospital of Chengdu Medical College), Lei Pan (Cangzhou Hospital of Integrated TCM-WM – Hebei), Hong Chen (The Second Affiliated Hospital of Harbin Medical University), Bo Wan (Siping Central People's Hospital), Li Lin (Fujian Zhangzhou Municipal Hospital), Ying-Hao Su (Hebei Provincial Hospital of TCM), Shu-yue Xia (Affiliated Central Hospital, Shenyang Medical College), Xiao Liu (Chengdu Fifth People's Hospital), Xin-da Yin (Zibo Central Hospital), Yong-long Xiao (Nanjing Drum Tower Hospital), Feng Li (Shanghai Chest Hospital), Pei-li Sun (Jiangsu People's Hospital), Wei-guo Xu (Mianyang Central Hospital), Hong-yan Li (Anyang People's Hospital), Jian Feng (Affiliated Hospital of Nantong Univertsity), Zhao-ping Yin (Panjin Liaoyou Gemflower Hospital), Man-yan Zhang (The First Affiliated Hospital of Nanhua University), Xian-wei Ye (Guizhou Provincial Hospital), Zong-hui Wei (Nanchuan People's Hospital), Guang-nan Liu (The Second Affiliated Hospital of Guangxi Medical University), Chao Cao (The Affiliated Hospital of Ningbo University), Xi-wen Gao (Shanghai Minhang Central Hospital), Han-bing Shi (The Third Affiliated Hospital of Qiqihar Medical University), Hui Zhou (Affiliated Hospital of Chengdu University), Feng Zhu (Wuxi Fifth People's Hospital), Wen-chao Gu (Shanghai Pudong New Area People's Hospital), Chang-li Yu (North China University of Science and Technology Affiliated Hospital), Feng Wu (Huizhou Third People's Hospital), Ya-lin Jiang (Bozhou People's Hospital), Jia-xi Feng (Zhejiang Taizhou Hospital), Wei-hua Zhang (Shangqiu First People's Hospital), Jun Wan (Affiliated Beijing Anzhen Hospital, Capital Medical University), Zong-jiao Shangguan (Rui'an People's Hospital), Xian-ming Zhang (Affiliated Hospital of Guizhou Medical University), Ping-fei Wang (Dazhou Central Hospital), Chang-qing Lin (Huizhou Central People's Hospital), Li Yan (Hebei Provincial People's Hospital), Ying-qun Zhu (Changsha Third Hospital), Yi-lan Sun (Zhejiang Provincial People's Hospital), Yu-feng Wan (Huai'an Second People's Hospital), Li Jiang (Affiliated Hospital of Chuanbei Medical College), Lu Guo (Sichuan Provincial People's Hospital), Hua Niu (Anhui Chest Hospital), Shu-tao Zou (Affiliated Bijie Hospital, Zhejiang Provincial People's Hospital), Xiao-he Zheng (The Affiliated Hospital of Shantou Medical University), Zi-li Meng (Huai'an First People's Hospital) and Xi-ya Wu (Jiangxi Provincial People's Hospital).
This clinical trial is prospectively registered with ClinicalTrials.gov as NCT06660992.
Ethics statement: The trial was conducted by following the Declaration of Helsinki, and the Good Clinical Practice. The trial protocol has been approved by The First Affiliated Hospital of Guangzhou Medical University and each participating site.
Author contributions: N-s. Zhong, J. Cao, Y. Feng, W-c. Liu, G-j. Zhang, H. Ye, Z-j. Liang, H. Shen, Z. Bao, Z-r. Yang, L-f. Min, H. Jiang, R. Qiu, Jian-p. Liang, J-l. Liu, L-m. Dong, X-y. Song, J-x. Wang, Y-m. Huang and W-j. Guan recruited patients and collected individual data; F-g. Li, L-y. Sun and H-m. Liu performed statistical analyses; W-j. Guan and N-s. Zhong contributed to study conception; W-j. Guan drafted the manuscript; all authors provided critical review of the manuscript and approved the final submission. All authors vouched for the data accuracy and completeness and the fidelity to the protocol.
Conflict of interest: W-j. Guan has received lecture fees and a scientific research grant from Haisco Co. Ltd The rest of the authors declared no interest directly related to the sponsor. F-q. Li, L-y. Sun and H-m. Liu are employees of Haisco Co. Ltd, and were involved in the study design and data analysis. The remaining the authors declare no other conflict of interest.
Support statement: This study was funded by Haisco Co. Ltd (Sichuan, China), and supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (number 2024ZD0529600), the Major Project of Guangzhou National Laboratory (grant number GZNL2024A02003), the National Natural Science Foundation (number 82470040), Guangzhou Science and Technology Plans (numbers 2024A04J6495, 2024A03J1206 and 2023B03J0407), and the Plan on Enhancing Scientific Research in Guangzhou Medical University (to W-j. Guan). The sponsor, Haisco Co. Ltd, jointly developed the study protocol with the first and last authors, supported research coordinators, and provided study drugs. The statistical team from the sponsor independently conducted statistical analyses. The sponsor had no influence on the decision to submit the manuscript for publication. Funding information for this article has been deposited with the Open Funder Registry.
Supplementary material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Protocol
00182-2026.SUPPLEMENT2
Supplementary material
00182-2026.SUPPLEMENT3
Statistical analysis plan
00182-2026.SUPPLEMENT4
Data availability
Baseline data of the HOPE-BE trial are available to collaborators through application. Please contact W-j. Guan (battery203@163.com) for further information.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
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Protocol
00182-2026.SUPPLEMENT2
Supplementary material
00182-2026.SUPPLEMENT3
Statistical analysis plan
00182-2026.SUPPLEMENT4
Data Availability Statement
Baseline data of the HOPE-BE trial are available to collaborators through application. Please contact W-j. Guan (battery203@163.com) for further information.