Severe Pneumonia Caused by Multidrug-resistant Gram-negative Bacterial Infection
Conditions
Keywords
Severe pneumonia, multidrug-resistant Gram-negative bacterial infection, traditional Chinese medicine, randomized controlled trial, Fei Re Qing Granules
Brief summary
This study aims to evaluate the clinical efficacy of a traditional Chinese medicine formula granule (Feireqing Granules) in the treatment of severe pneumonia caused by multidrug-resistant Gram-negative bacterial infections (MDR-GNB severe pneumonia), to establish a therapeutic regimen, and to generate high-quality clinical evidence.
Detailed description
This study evaluates the efficacy and safety of Feireqing Granules for MDR-GNB severe pneumonia through a multicenter, randomized, double-blind, placebo-controlled trial. Key elements of the trial include: Design: Conducted across multiple centers, comparing Feireqing Granules and placebo groups, alongside standard guideline-based modern medical treatment. Participants: Patients diagnosed with MDR-GNB severe pneumonia according to modern medical diagnostic criteria, aged ≥18 years and \<80 years. 76 patients will be enrolled in each group. Intervention: Test group: Participants will receive Feireqing Granules in combination with standard modern medical treatments. Control group: Participants will receive placebo granules (matching the appearance, weight, color, and odor of the active granules, composed mainly of starch, dextrin, microcrystalline cellulose, and 5% active drug) in combination with standard modern medical treatments. Outcomes: Primary efficacy indicator: All-cause mortality. Secondary indicators: Clinical cure rate, bacterial clearance rate, duration of antibiotic therapy, effective mechanical ventilation rate, length of hospital stay, Clinical Pulmonary Infection Score (CPIS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score. Study Duration: Treatment for 14 days, with a 28-day follow-up. This trial seeks to confirm the clinical efficacy of Feireqing Granules in treating MDR-GNB severe pneumonia and to provide high-quality evidence for the long-term and objective evaluation of TCM interventions.
Interventions
Fei Re Qing Granules (Ingredients: Scutellaria baicalensis \[Huang Qin\], Trichosanthes kirilowii \[Gua Lou\], Forsythia suspensa \[Lian Qiao\], Fritillaria thunbergii \[Zhe Bei Mu\], etc.). Routine standard treatments：Routine standard treatments according to clinical guidelines.
DRUGPlacebo of Feireqing Granules
Placebo of Feireqing Granules：The placebo granules are prepared using 5% of the active drug combined with pharmaceutical excipients, including starch, dextrin, microcrystalline cellulose, and food-grade coloring and flavoring agents, to ensure consistency in appearance, weight, color, and odor with the Fei Re Qing Granules. Routine standard treatments：Routine standard treatments according to clinical guidelines.
Sponsors
Henan University of Traditional Chinese Medicine
Henan Provincial Hospital of TCM
Third Affiliated Hospital of Henan University of Traditional Chinese Medicine
Henan Provincial People's Hospital
The First Affiliated Hospital of Zhengzhou University
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Meeting the diagnostic criteria for severe pneumonia, aged ≥18 years and \<80 years; * Microbiological culture confirming Gram-negative bacterial infection resistant to three or more classes of antibiotics, such as extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii (CRAB), and multidrug-resistant Pseudomonas aeruginosa (MDR-PA); * Written informed consent obtained from the patient or their legal representative.
Exclusion criteria
* Pregnant or breastfeeding women; * Patients with impaired consciousness, dementia, psychiatric disorders, or other conditions that preclude effective communication and cooperation; * Patients with aspiration pneumonia, fungal pneumonia, viral pneumonia, pulmonary tuberculosis, or HIV-associated Pneumocystis jirovecii pneumonia; * Patients with severe hepatic or renal insufficiency, such as liver cirrhosis with Child-Pugh score of 10-15, or estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m²; * Patients with hematologic malignancies, solid organ transplantation, or congenital/acquired diseases leading to immunodeficiency; * Patients with multidrug-resistant bacterial infections outside the lung (e.g., urinary tract, abdominal cavity, bloodstream); * Patients with severe cardiac dysfunction (NYHA class IV), malignant arrhythmias, or other hemodynamically unstable conditions; * Patients who have already received antimicrobial therapy for more than one week; * Patients who have participated in another drug clinical trial within one month prior to enrollment; * Patients with known allergy to the investigational drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | All-cause mortality: assessed at 14 and 28 days post-enrollment. | All-cause mortality will be assessed as the proportion of participants who die from any cause during the study period. Mortality will be recorded at Day 14 and Day 28 after enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure rate | Evaluations will be conducted on treatment Day 0, Day 14 and during follow-up on Day 28. | According to the Technical Guidelines for Clinical Trials of Antibacterial Drugs, clinical cure is defined as the complete resolution or normalization of all symptoms and signs present at baseline at the post-treatment visit, along with normalization of non-microbiological indicators such as imaging and laboratory tests. In practice, some clinical symptoms or signs, or abnormalities in non-microbiological indicators, may still be observed at the post-treatment visit. If these findings are physiological, reflect post-infection status, or are related to underlying diseases rather than active infection, they may also be considered indicative of clinical cure. |
| Bacterial clearance rate | Treatment days 0, days 7, and days 14. | Based on microbiological testing during hospitalization. Pathogen-targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid or sputum, or sputum culture, is performed on treatment days 0, 7, and 14 for evaluation. |
| Duration of antibiotic use | From Day 0 of treatment to Day 28 of follow-up | Total number of days of antibiotic therapy during hospitalization, including both intravenous and oral administration. |
| Invasive mechanical ventilation rate | From Day 0 of treatment to Day 28 of follow-up | The invasive mechanical ventilation rate will be assessed as the proportion of participants who require invasive mechanical ventilation during the study period. Eligible participants are those not receiving invasive ventilation at baseline (Day 0). The outcome is defined as the need for endotracheal intubation and mechanical ventilation due to clinical deterioration, including worsening hypoxemia, hypercapnia, or respiratory failure. The rate will be calculated as the number of participants requiring invasive mechanical ventilation divided by the total number of participants at risk, from Day 0 of treatment to Day 28 of follow-up. |
| Length of hospital stay | From Day 0 of treatment to Day 28 of follow-up | Total number of days of hospitalization |
| Clinical Pulmonary Infection Score (CPIS) | Assessed on treatment days 0, 7, and 14, and on follow-up days 14 and 28. | The Clinical Pulmonary Infection Score (CPIS) will be used to evaluate the presence and severity of pulmonary infection. The CPIS is calculated based on a composite of clinical, radiological, and laboratory parameters, including body temperature, leukocyte count, tracheal secretions, oxygenation (PaO₂/FiO₂), chest radiograph findings, and culture results of tracheal aspirate. Each component is scored from 0 to 2 points, with a maximum total score of 12; higher scores indicate more severe infection. CPIS will be assessed on treatment days 0, 7, and 14, as well as on follow-up days 14 and 28. |
| SOFA score | Recorded on treatment days 0, 7, and 14, and on follow-up days 14 and 28. | The Sequential Organ Failure Assessment (SOFA) score will be used to evaluate the extent of organ dysfunction during the study. The SOFA score includes six components: respiratory function (PaO₂/FiO₂ ratio), coagulation (platelet count), liver function (bilirubin), cardiovascular status (mean arterial pressure or vasopressor requirement), central nervous system function (Glasgow Coma Scale), and renal function (serum creatinine or urine output). Each organ system is scored from 0 (normal) to 4 (severe dysfunction), with a total score ranging from 0 to 24. Higher scores indicate more severe organ dysfunction and higher risk of mortality. SOFA scores will be assessed on treatment days 0, 7, and 14, and on follow-up days 14 and 28. |
| Acute Physiology and Chronic Health Evaluation II (APACHE II) score | From Day 0 of treatment to Day 28 of follow-up | The Acute Physiology and Chronic Health Evaluation II (APACHE II) score will be used to evaluate the severity of illness and the risk of mortality. The score incorporates the acute physiology score, age score, and chronic health score. Higher total scores indicate more severe illness and greater mortality risk. APACHE II scores will be recorded on treatment days 0, 7, and 14, and on follow-up days 14 and 28. |
Countries
China
Contacts
CONTACTZhenzhen Feng, Doctor
STUDY_CHAIRJiansheng Li, Doctor
The First Affiliated Hospital of Henan University of Traditional Chinese Medicine
Outcome results
None listed