FuKe Qianjin Capsule Plus Antibiotics for Chronic Endometritis

This is a rigorously designed randomized, double-blind, single-dummy, multicenter interventional clinical study initiated to address the unmet clinical needs in the treatment of chronic endometritis (CE), a common chronic inflammatory gynecological disorder with a rising incidence in reproductive-age women. Led by Principal Investigator Xue Fengxia at Tianjin Medical University General Hospital, which serves as both the study sponsor and the primary clinical trial institution, the research is funded by Zhuzhou Qianjin Pharmaceutical Co., Ltd.-the exclusive manufacturer of Fuke Qianjin Capsule, the core traditional Chinese medicine (TCM) intervention in this study. The study adheres to international clinical research norms and national ethical and regulatory requirements, with full oversight by the Institutional Ethics Committee of Tianjin Medical University General Hospital, ensuring the scientificity, rigor, and ethical compliance of all research procedures and participant protections. Chronic endometritis is defined by persistent plasma cell infiltration in the endometrial stroma, caused by bacterial invasion of the endometrium via ascending or descending pathways through the reproductive tract or lymphatic system. A striking clinical challenge of CE is its non-specific or even absent symptomatic presentation; affected patients may experience mild or atypical symptoms such as abnormal uterine bleeding, pelvic pain, dyspareunia, and abnormal vaginal discharge, which are often overlooked in routine clinical practice. Compounding this issue, conventional clinical assessments-including peripheral blood inflammatory markers (e.g., white blood cell count, serum C-reactive protein) and gynecological imaging (e.g., color Doppler ultrasound, hysterosalpingography)-lack specific diagnostic signs for CE, leading to frequent underdiagnosis and delayed treatment. Epidemiological data highlight the significant clinical burden of CE: its incidence ranges from 2.8% to 56.8% in infertile women, 14.0% to 67.5% in patients with repeated implantation failure (RIF), and 9.3% to 67.6% in those with recurrent miscarriage (RM), establishing a clear and strong link between unmanaged CE and adverse reproductive outcomes. Despite its clinical importance, there is no currently approved specific treatment regimen for CE worldwide; clinical practice relies on empirical antibiotic therapy, with doxycycline as the first-line agent and second-line combination regimens including metronidazole paired with fluoroquinolones (moxifloxacin, ofloxacin, ciprofloxacin). However, long-term and irregular antibiotic use has led to the emergence of bacterial drug resistance, resulting in suboptimal treatment efficacy in a substantial proportion of CE patients, as well as increased risks of secondary complications such as superinfection and dysbiosis of the reproductive tract flora-creating an urgent need for safe and effective adjunctive therapies to improve treatment outcomes and reduce antibiotic reliance. Against this backdrop, the study leverages the well-documented clinical value of integrated TCM and Western medicine (TCM-WM) in managing chronic inflammatory diseases, evaluating the synergistic efficacy and safety of Fuke Qianjin Capsule combined with standard antibiotic therapy for CE. Fuke Qianjin Capsule is a nationally recognized TCM preparation, listed in both the National Essential Drugs List and the Class A National Medical Insurance List (National Medicine Approval Number Z20020024), with a long history of clinical use in treating gynecological inflammatory disorders including chronic pelvic inflammatory disease, chronic endometritis, and chronic cervicitis. Formulated with eight carefully selected medicinal herbs-Flemingia philippinensis, Rosa laevigata root, Andrographis paniculata, Mahonia fortunei, Zanthoxylum nitidum, Angelica sinensis, Spatholobus suberectus, and Codonopsis pilosula-the capsule exerts a synergistic therapeutic effect by tonifying qi and blood, clearing heat and eliminating dampness, and activating blood circulation to dissipate stasis. This formulation aligns precisely with the TCM pathological understanding of CE, which is categorized under "leukorrheal diseases", "lower abdominal pain in women", and "dysmenorrhea" and attributed to damp-heat stasis obstruction combined with qi and blood deficiency-pathogenic factors linked to postpartum uterine collateral weakness, internal invasion of pathogenic toxins, and constitutional deficiency. Domestic preclinical and clinical research has demonstrated that Fuke Qianjin Capsule can alleviate endometrial inflammation, reduce bacterial drug resistance, lower the recurrence rate of gynecological inflammatory disorders, and improve reproductive tract microenvironment-making it a promising adjunct to antibiotic therapy for CE. Notably, the capsule has a well-characterized post-marketing safety profile, with mild and transient adverse reactions reported, further supporting its suitability for long-term use in chronic disease management. To minimize bias and ensure the reliability of study results, the research adopts a double-blind, single-dummy study design-a gold-standard methodological approach for evaluating herbal interventions alongside standard Western medicine regimens. The double-blind design ensures that both study participants and investigators remain unaware of group assignments throughout the active treatment phase and primary efficacy assessments, eliminating subjective bias in symptom reporting, clinical evaluation, and adverse event recording. The single-dummy design addresses the practical challenge of blinding in TCM-WM combination therapy: all participants receive the identical standard antibiotic regimen (the clinical gold standard for CE), with the experimental group receiving Fuke Qianjin Capsule and the control group receiving a matched placebo of Fuke Qianjin Capsule (identical in appearance, dosage form, administration frequency, and taste). This design maintains the integrity of blinding while ensuring that all participants receive the standard of care antibiotic treatment, upholding ethical principles of clinical research. The study is planned to be conducted across 10-15 clinical centers in China, a multicenter design that enhances the generalizability of study results by enrolling a diverse cohort of participants from different geographical regions, with varying clinical practices and patient demographics-critical for translating research findings into widespread clinical practice. The study aims to enroll a total of 300 eligible female participants, with a 1:1 random allocation to the experimental group (150 participants) and the control group (150 participants). Eligibility criteria are strictly defined to ensure the homogeneity of the study cohort and the validity of efficacy and safety assessments: participants must be aged 20 to 40 years (a reproductive age range that aligns with the primary population affected by CE and its reproductive complications), have a confirmed diagnosis of CE via gold-standard diagnostic methods (hysteroscopy with clinical scoring and pathological examination including HE staining and CD138 immunohistochemical staining-the definitive diagnostic marker for CE), conform to the TCM syndrome differentiation of damp-heat complicated by deficiency of both qi and blood (to ensure alignment with the therapeutic indications of Fuke Qianjin Capsule), and have a regular menstrual cycle (21 ≤ cycle ≤ 35 days). A comprehensive set of exclusion criteria is implemented to exclude participants with confounding conditions that may impact study outcomes or pose additional safety risks, including acute genital tract or pelvic infection (to avoid overlapping inflammatory processes), endometrial tuberculosis, gynecological malignancies (e.g., endometrial cancer) or severe endometrial lesions (e.g., hyperplasia, intrauterine adhesion, submucous myoma, polyps), hydrosalpinx or pelvic abscess, severe cardiac, hepatic, or renal dysfunction, uncontrolled autoimmune or endocrine/metabolic diseases (e.g., systemic lupus erythematosus, diabetes mellitus), mental illnesses that impede follow-up cooperation, pregnancy or lactation (or refusal of contraception during treatment), hypersensitivity to any component of the study drugs (Fuke Qianjin Capsule or doxycycline hyclate), participation in other clinical trials within the previous 3 months, and any other conditions deemed unsuitable for participation by the investigating physician. All enrolled participants receive the first-line antibiotic therapy for CE: doxycycline hyclate tablets (100mg per tablet), administered orally at a dosage of 1 tablet twice daily for a consecutive 14 days-this short-term antibiotic course targets the bacterial etiology of CE, eliminating the pathogenic microorganisms causing endometrial inflammation. The experimental group is administered Fuke Qianjin Capsule (0.4g per capsule) for a consecutive 56 days, with an oral dosage of 2 capsules three times daily, initiated concurrently with the antibiotic regimen. The control group is administered a matched Fuke Qianjin Capsule placebo for the same 56-day duration and identical dosage, ensuring that the only variable between the two groups is the active TCM component. The 56-day duration of the Fuke Qianjin Capsule/placebo intervention is a deliberate study design choice, tailored to the chronic and recurrent nature of CE: while the 14-day antibiotic course addresses acute bacterial infection, the longer TCM intervention is intended to exert sustained anti-inflammatory effects, repair damaged endometrial tissue, improve the reproductive tract microenvironment, and prevent disease recurrence-addressing the unmet need for long-term disease management in CE. All study medications (Fuke Qianjin Capsule, placebo, and doxycycline hyclate tablets) are provided to participants using standardized drug dispensing and collection procedures to ensure medication adherence. Participants are given diary cards to record medication intake, symptom changes, and concomitant medication use. Research staff perform regular checks to monitor and improve adherence. The total study timeline for each participant spans approximately 8 months, encompassing three distinct phases: a screening/baseline period (up to 28 days), a 56-day active treatment phase, and a 6-month post-treatment follow-up period. Structured in-person study visits are scheduled at key time points to conduct diagnostic assessments, efficacy evaluations, safety monitoring, and drug management, with additional post-treatment follow-up conducted via outpatient visit or telephone to capture long-term outcomes-particularly reproductive outcomes, which are the primary patient-centric endpoints for the target population. The screening/baseline period (Visit 1: Day -28 to 0) involves a comprehensive set of assessments to confirm eligibility: signed informed consent, collection of demographic and clinical data (including medical history, medication history, and reproductive history), gold-standard CE diagnosis (hysteroscopy and pathological examination), TCM syndrome scoring, routine gynecological examinations (vaginal discharge routine), color Doppler ultrasound, and comprehensive safety monitoring (vital signs, blood routine, blood biochemistry, blood pregnancy test). Eligible participants are then randomly assigned to the experimental or control group, with study drugs and diary cards dispensed, and follow-up visits scheduled. During the active treatment phase, two in-person visits are conducted: Visit 2 (Day 28 ± 5 of medication) includes TCM syndrome scoring, color Doppler ultrasound (with supplementary examination if the menstrual clean-up window is missed), safety monitoring, recording of concomitant medications and adverse events, and collection of residual drugs and diary cards; Visit 3 (Day 56 ± 7 of medication)-the end of the active treatment phase-involves repeat gold-standard CE efficacy assessments (hysteroscopy and pathological examination), TCM syndrome scoring, color Doppler ultrasound, comprehensive safety monitoring, and recording of adverse events and concomitant medications, with final drug collection and diary card retrieval. The post-treatment follow-up phase includes two key time points (Visits 4 and 5: 3 and 6 months after the end of treatment), focusing on the collection of clinical pregnancy rate-the primary long-term outcome measure-defined as the presence of one or more gestational sacs confirmed by ultrasound examination following a positive blood or urine pregnancy test. This outcome measure is selected for its clinical relevance, as it directly addresses the primary reproductive concerns of the study's target population (infertile women, those with RIF or RM) and reflects the real-world clinical benefit of CE treatment. Safety is a core priority of the study, with systematic and comprehensive safety monitoring conducted at all study visits and throughout the entire study period. Adverse events (AEs) are actively and passively collected: research staff conduct regular inquiries about participant symptoms, and participants are instructed to report any unexpected physical discomfort promptly. All AEs are documented in detail, including the onset time, duration, severity, clinical manifestation, intervention measures, and outcome, with causal relationship assessments conducted to determine the association with study drugs or procedures. The study accounts for the known safety profiles of both study interventions: Fuke Qianjin Capsule has a well-documented post-marketing safety profile, with mild and transient adverse reactions including gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea, abdominal distension), skin reactions (rash, pruritus), neurological symptoms (dizziness, headache, insomnia), and occasional allergic or anaphylactoid reactions; doxycycline hyclate, a tetracycline antibiotic, has known potential adverse effects including gastrointestinal reactions, hepatotoxicity, allergic reactions (including photosensitivity), hematological abnormalities, benign intracranial hypertension, superinfection, and vitamin deficiency due to flora disturbance. In addition to drug-related safety monitoring, the study addresses the procedural risks of hysteroscopy-the gold-standard diagnostic and efficacy assessment tool for CE-which, while generally safe, carries rare but potential risks including uterine perforation, infection, fluid overload, bleeding, air embolism, and cervical laceration. Standardized procedural protocols and emergency response plans are implemented at all study centers to minimize these risks, with trained medical staff conducting all hysteroscopy procedures and on-site emergency equipment and medications available to manage any complications promptly. The study upholds the highest standards of participant privacy, confidentiality, and ethical protection. All personal and clinical data of participants are collected, stored, and processed in accordance with national data protection laws and regulations, with strict de-identification measures implemented for all study data used for analysis and reporting. Participant medical records (including study medical records, examination reports, and adverse event records) are stored securely at the participating clinical centers, with access restricted to authorized research staff only. Biological specimens collected during the study (e.g., endometrial tissue for pathological examination) are used exclusively for study-related research purposes, with no commercial use permitted; all specimens are anonymized, with strict confidentiality measures to protect participant identity, and will be properly handled (stored or destroyed) in accordance with the guidelines of the Institutional Ethics Committee and national regulatory requirements. Participants retain full voluntary participation rights throughout the study: they may withdraw from the study at any time, for any reason, without any adverse impact on their standard medical care or treatment relationships with their healthcare providers. If important new information about the study drugs or procedures emerges during the research that may impact participants' willingness to continue, they will be promptly informed, and the informed consent form will be updated as needed, with re-consent obtained for continued participation. The primary objective of this study is to evaluate the efficacy and safety of Fuke Qianjin Capsule combined with standard antibiotic therapy for the treatment of CE (in patients with damp-heat complicated by qi and blood deficiency). Secondary objectives include assessing the long-term clinical benefit of the integrated regimen (reflected by the clinical pregnancy rate at 3 and 6 months post-treatment), evaluating the effect of the regimen on reducing CE recurrence. The study is expected to generate high-quality clinical evidence to address the current gaps in CE treatment: if the integrated TCM-WM regimen is found to be superior to antibiotic monotherapy in improving clinical efficacy, reducing disease recurrence, and maintaining a favorable safety profile, the findings will support the clinical adoption of Fuke Qianjin Capsule as an evidence-based adjunct to antibiotic therapy for CE. This will provide clinicians with a new, safe, and effective treatment option for CE, addressing the unmet need for long-term disease management and reducing reliance on antibiotics-thus mitigating the risk of drug resistance. For patients, the study has the potential to improve clinical outcomes, alleviate CE-related symptoms, and enhance reproductive health-particularly for those struggling with infertility, RIF, and RM due to unmanaged CE. Beyond its direct clinical implications, the study will contribute to the growing body of high-quality evidence for the integration of TCM and Western medicine in the management of chronic inflammatory diseases, advancing a patient-centered, personalized approach to gynecological care and providing a model for future research on TCM-WM combination therapy. The study results will be disseminated through peer-reviewed medical journals, academic conferences, and clinical practice guidelines, ensuring that the research findings translate into tangible benefits for clinicians and patients worldwide.