Efficacy and Safety of Colistimethate Sodium for Injection in The Treatment of Carbapenem-Resistant Enterobacteriaceae Infection

• Status: Recruiting
• Trial end date: 2025-11-30
• Target enrollment: 0
• Participant gender: All

Summary

Colistin can be used to treat the infection caused by carbapenem-resistant enterobacteriaceae(CRE). In China, patients diagnosed with Hospital-acquired-pneumonia (HAP)or bloodstream infection caused by CRE are recruited, and randomly assigned to two groups, and in one group the patients accept treatment with colistin, however in another group, the patients accept treatment without colistin. The efficacy and safety of the treatment between the two groups are compared.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Southeast University, China
• Treatments: Colistin

Criteria

Inclusion Criteria:

1. Patients who can provide written informed consent or their informed consent can be provided by legal guardian

2. Patients who are hospitalized

3. Adults ≥18 years and ≤90 years of age

4. Patients suspected of or diagnosed with hospital-acquired pneumonia (HAP, in a patient hospitalised for more than 48 hours or developing within 7 days after discharge from a hospital) or bloodstream infection caused carbapenem-resistant enterobacteriaceae (CRE) based on the culture results of the sample collected 72h before the randomization or rapid diagnostic detection.

Rapid testing of respiratory or blood specimens utilizing Digital PCR(dPCR) technology should be used to enable early identification of CRE infection pneumonia. Patients can be randomized based on the results of the rapid test while awaiting results of cultures from the local laboratory. However, if the sample does not grow CRE in the local microbiology laboratory culture, these patients will be withdrawn from the study drug treatment.

Patients with HAP should fulfil one of the following systemic signs: 1)Fever (temperature >38°C) or hypothermia (rectal/core temperature <35°C);2)White blood cell (WBC) count >10,000 cells/mm3, or WBC count <4500 cells/mm3, or >15% band forms and fulfil at least two of the following respiratory signs or symptoms:1)a new onset of cough (or worsening of cough);2)production of purulent sputum or endotracheal secretions;3)auscultatory findings consistent with pneumonia/pulmonary consolidation (e.g., rales, rhonchi, bronchial breath sounds, dullness to percussion, egophony);4)dyspnoea, tachypnoea or hypoxaemia (O2 saturation <90% or pO2 <60 mmHg while breathing room air).

Patients with bloodstream infection should fulfil one of the following criterion:1)fever(≥38 ℃);2)chills;3)hypotension(systolic <90 mmHg, requiring vasopressors to maintain mean arterial pressure ≥60 mmHg,decreased by 30mmHg from baseline) ,and isolation of CRE from at least two blood culture collected from two different sites.

5. Respiratory or blood specimen obtained for culture within 72 hours prior to randomization, and after the onset of signs and symptoms of HAP or bloodstream infection (ideally before receipt of any systemic antibiotics).

6. Patients whose APACHE II score is between 10 and 30.

Exclusion Criteria:

1. Patients who received polymyxin in the 72 hours prior to randomization.

2. Patients who received antibiotics more than 24 hours in the 72 hours prior to randomization, and after treatment，conditions of patients improved.

3. Patient with history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to Colistimethate Sodium for Injection or other ingredients of it.

4. Evidence of active concurrent pneumonia requiring additional antimicrobials treatment caused by Streptococcus pneumoniae，Haemophilus influenzae，Methicillin-resistant staphylococcus aureus，Vancomycin-resistant enterococcus，Mycoplasma pneumonia，Legionella pneumophila, respiratory syncytial virus, influenza virus, parainfluenza virus, Middle East Respiratory Virus, Mycobacteria, Aspergillus, Mucormycosis, Candida,etc. If these organisms are identified but it is deemed by the Investigator that no treatment is warranted and their presence does not significantly change the prognosis of the patient, then the patient may be considered for this study.

5. Patients who are diagnosed with primary lung cancer (including small cell lung cancer/non-small cell lung cancer patients) or other malignancy transferred to the lungs or other known post obstructive pneumonia. Patients who is known or suspected of active tuberculosis, cystic fibrosis, lung abscess, pyothorax or obstructive pneumonia.

6. Patients with hematological malignancy such as leukemia, lymphoma and multiple myeloma.

7. Patients with lung/heart transplantation or stem cell transplantation.

8. Patient was immunocompromised and at risk of infection by opportunistic pathogens including, but not limited to the following:1) HIV (AIDS or CD4 <200). 2) chemoradiotherapy within 3 months prior to randomisation. 3) Immunosuppressive therapy including maintenance corticosteroids (0.5 mg/kg prednisone per day or other equivalent glucocorticoid). 4) Absolute neutrophil count <500/mm3.

9. Patients with CKD receiving haemodialysis or peritoneal dialysis.

10. Patients with an estimated creatinine clearance (CrCL) <16 mL/min when randomization is conducted.

11. Patients expected to require haemodialysis or other renal support while on study therapy.

12. Patients with chronic liver failure with portal hypertension, acute hepatic failure or acute decompensation of chronic hepatic failure.

13. Patient had past or current history of epilepsy or seizure disorders, excluding febrile seizures of childhood.

14. Patients who participated in other clinical trials within three months.

15. Patient was pregnant or breastfeeding. If either urine or serum β-hCG test was positive, the patient was excluded.

16. Patient who have been previously enrolled in this study.

17. Other conditions exist researchers thought are not suitable.