Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB)
Conditions
Interventions
Intervention group:Colistimethate Sodium + carbapenems (including meropenem, imipenem/cilastatin, or biapenem)
Sponsors
Tangdu Hospital of the Fourth Military Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients must meet all the following inclusion criteria to be enrolled in the study: 1. Male or female, aged >= 18 years; 2. Specimens collected from the primary infection site within 7 days prior to randomization (based on the collection date) are confirmed by bacterial culture to contain at least one carbapenem-resistant gram-negative bacteria (CR-GNB) susceptible to colistimethate sodium, including but not limited to carbapenem-resistant Enterobacterales (CRE) and/or Pseudomonas aeruginosa; Note: If the specimen culture reveals two or more CR-GNB, all bacterias must be susceptible to colistimethate sodium. 3. During screening, as determined by the investigator, the patient requires inpatient intravenous antibiotic therapy for a duration meeting at least the following criteria, with an expected survival of >= 28 days: (1) At least 7 days for patients with HAP/VAP; (2) At least 5 days for patients with cIAI; (3) At least 7 days for patients with BSI; 4. Sufficient baseline samples (e.g., respiratory secretions, blood, peritoneal effusion) are available for Gram staining and bacterial culture within 48 hours prior to the first dose of study intervention; 5. Patients diagnosed with HAP/VAP; 6. Patients diagnosed with cIAI; 7. Patients diagnosed with BSI (including bloodstream infections caused by infections other than HAP/VAP and cIAI); 8. During the study and within 30 days after the last dose of intervention, female patient of childbearing potential or male patient who has female partner of childbearing potential, agree to use effective contraceptive methods and refrain from donating sperm or eggs. Female patient of childbearing potential must have a negative blood or urine pregnancy test prior to randomization and be non-lactating. 9. Understand and agree to comply with the study procedures and methods, voluntarily participate in the study, and provide written informed consent.
Exclusion criteria
Exclusion criteria: Patients with any of the following criteria will be excluded from the study: 1. Received >24 hours of potentially effective systemic antimicrobial therapy within 72 hours prior to the first dose (e.g., more than 3 doses of antimicrobials administered every 8 hours, more than 2 doses every 12 hours, or more than 1 dose every 24 hours); Other than patients who failed the current antimicrobial therapy (defined as persistent or worsening infection-related signs/symptoms, or drug resistance confirmed by specimen culture after receiving >=48 hours of antimicrobial therapy); 2. Acute Physiology and Chronic Health Evaluation (APACHE II) score >30; 3. HAP/VAP patients with any of the following: (1) Confirmed or suspected community-acquired bacterial pneumonia (CABP); (2) Concomitant nebulized therapy with agents having anti-Gram-negative activity; (3) Confirmed or suspected viral, fungal, or parasitic pneumonia; (4) Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia (HAP/VAP) caused by obstruction, including lung cancer, other malignant diseases metastasizing to the lungs leading to obstruction, or other obstructions; (5) Other lung diseases that may interfere with efficacy assessment as determined by the investigator, such as active pulmonary tuberculosis, cystic fibrosis, or granulomatous lung diseases; 4. cIAI patients with any of the following: (1) Persistent or recurrent peritonitis after appropriate treatment of secondary peritonitis (i.e., tertiary peritonitis); (2) Intra-abdominal abscesses that cannot be treated by surgical intervention including drainage; (3) Complicated Intra-Abdominal Infection (cIAI) requiring staged abdominal repair or open abdomen after abdominal surgery; (4) Concomitant confirmed or suspected intra-abdominal infection caused by fungi, parasites, viruses, or Mycobacterium tuberculosis; (5) Acute gastroduodenal or small bowel perforation surgically treated within =65 mmHg and a serum lactate level >2 mmol/L); 7. Planned to use prohibited medications specified in the protocol during the study; 8. Concomitant conditions that may interfere with the efficacy assessment of the study interventions, such as endocarditis, osteomyelitis, meningitis, prosthetic joint infection, non-drainable/undrained abscesses, or bloodstream infections associated with non-removable prostheses/devices/catheters/intravascular grafts; 9. Any of the following: (1) History of allergy to polymyxin preparations, carbapenems, or their excipients; (2) History of severe allergies (e.g., anaphylactic shock); 10. Patients with renal impairment receiving hemodialysis or peritoneal dialysis; 11. Immunocompromised patients, such as those with tumors requiring radiation or chemotherapy within 6 weeks prior to randomization or during the study, or those receiving immunosuppressive therapy including corticosteroid therapy (>40 mg/day prednisolone or equivalent dose of other glucocorticoids); 12. Blood neutrophil count <0.5×10^9/L; 13. HIV antibody-positive; 14. History of drug abuse (non-medical use of narcotic or p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Patient mortality rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of patients with different microbiological and composite efficacy outcomes in the m-mITT population.;Proportion of patients with different clinical, microbiological, and composite efficacy outcomes by infection type in the m-mITT population.;Proportion of patients with clinical cure in the CE population;Proportion of patients with clinical cure, microbiological eradication, and composite cure in the ME population;Proportion of patients with clinical cure, microbiological eradication, and composite cure by different carbapenem-resistant bacterial species in the m-mITT population;All-cause Mortality in the ME Population;Proportion of patients with different clinical efficacy in the m-mITT population;Proportion of patients with different clinical efficacy in the CE population;Proportion of patients with different clinical efficacy and microbiological efficacy in the ME population;Proportion of patients with different microbiological efficacy by different carbapenem-resistant bacterial species in the m-mITT population;Proportion of patients with different microbiological efficacy by different carbapenem-resistant bacterial species in the ME population; | — |
Countries
China
Contacts
Public ContactLiu Linna
Tangdu Hospital of the Fourth Military Medical University
Outcome results
None listed