Using Colistimethate Sodium to Treat Infections from Carbapenem-Resistant Bacteria

Colistimethate Sodium for Injection in The Treatment of Carbapenem-Resistant Enterobacteriaceae Infection：a Prospective, Open-label, Randomized Controlled, Multicenter Clinical Trial

This study is testing if colistimethate sodium can help hospitalized patients with infections from tough-to-treat bacteria feel better compared to standard treatments.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 404 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Southeast University, China (Academic / other)
• Drugs / interventions: prednisone
• Locations: 15 sites (Hefei, Anhui and 14 other locations)
• Trial ID: NCT06051513 on ClinicalTrials.gov

What this trial studies

This study investigates the efficacy and safety of colistimethate sodium for treating infections caused by carbapenem-resistant Enterobacteriaceae (CRE) in hospitalized patients. Patients diagnosed with hospital-acquired pneumonia or bloodstream infections will be randomly assigned to receive either colistin or standard treatment without it. The study will assess various outcomes, including mortality rates and clinical cure rates, over a 14-day period. Conducted in multiple centers across China, the study adheres to good clinical practice guidelines and ethical standards.

Who should consider this trial

Good fit: Ideal candidates are hospitalized adults aged 18 to 85 diagnosed with hospital-acquired pneumonia or bloodstream infections caused by CRE.

Not a fit: Patients who do not have a confirmed diagnosis of CRE infection or those whose cultures do not grow CRE will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients suffering from severe infections caused by antibiotic-resistant bacteria.

How similar studies have performed: While the use of colistin has been explored in other studies, this specific approach targeting CRE infections is novel and aims to provide clearer efficacy and safety data.

Eligibility 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 ≤85 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 5 days before the randomization or rapid diagnostic detection.

   Rapid testing of respiratory or blood specimens 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 5 days 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 for more than 48 hours 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 chronic liver failure with portal hypertension, acute hepatic failure or acute decompensation of chronic hepatic failure.
10. Patients who participated in other clinical trials within three months.
11. Patient was pregnant or breastfeeding. If either urine or serum β-hCG test was positive, the patient was excluded.
12. Patient who have been previously enrolled in this study.
13. Patients who have condionts that may affect the trial.
14. Other conditions exist researchers thought are not suitable.

Where this trial is running

Hefei, Anhui and 14 other locations

• Anhui Provincial People's Hospital — Hefei, Anhui, China (Recruiting)
• The First Hospital of Anhui Medical University — Hefei, Anhui, China (Recruiting)
• Jinjiang Municipal Hospitall — Jinjiang, Fujian, China (Recruiting)
• Huai'an First People's Hospital — Huai'an, Jiangsu, China (Recruiting)
• The First Hospital of Lianyungang — Lianyungang, Jiangsu, China (Recruiting)
• Zhongda Hospital Affiliated to Southeast University — Nanjing, Jiangsu, China (Recruiting)
• Affiliated Hospital of Nantong University — Nantong, Jiangsu, China (Recruiting)
• Suzhou Municipal Hospitial — Suzhou, Jiangsu, China (Recruiting)
• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• JiangsuTaizhou People's Hospital — Taizhou, Jiangsu, China (Recruiting)
• Wuxi No.2 People's Hospital — Wuxi, Jiangsu, China (Recruiting)
• Xuzhou Central Hospital — Xuzhou, Jiangsu, China (Recruiting)
• Yancheng No.1 People's Hospital — Yancheng, Jiangsu, China (Recruiting)
• Northern Jiangsu People's Hospital — Yangzhou, Jiangsu, China (Recruiting)
• Yixing People's Hospital — Yixing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Yingzi Huang, MD

Conditions Carbapenem-Resistant Enterobacteriaceae Infection; Colistimethate Sodium for Injection; Hospital-acquired pneumonia; Bloodstream infection; Carbapenem-resistant Enterobacteriaceae