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

NCT06051513 | Recruiting DMC

• 1 other identifier: COUNT-CRE
• Study Type: interventional
• Target: 404
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Carbapenem-Resistant Enterobacteriaceae Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 14-day all cause mortality

  the proportion of subjects who die within 14 days after randomization to the number of subjects in each group

  from randomization to day 14

Secondary Outcomes (8)

• 14-day clinical cure rate

  from randomization to day 14

• 14-day efficacy rate

  from randomization to day 14

• ICU free days within 28 days after randomization

  from randomization to day 28

• 14-day microbiological cure rate

  from randomization to day 14

• incidence of adverse events and severe adverse events within first 28 days

  from randomization to day 28

Study Arms (2)

colistin group

EXPERIMENTAL

For patients in this group, colistin based therapy is used. Colistin combined with metroperan or imipenem（MIC≤8mg/L），or colistin combined with tigecycline, or colistin combined with aminoglycosides (amikacin) are suggested to treat patients diagnosed with hospital-acquired pneumonia or bloodstream infection caused by carbapenem-resistant enterobacteriaceae. At the beginning of the intravenous use of Colistimethate Sodium for Injection，the load dose is 300mg CBA(about 9 million U)，and after 12-24 hours，the first maintenance dose should be given. The daily maintenance dose was 300-360mg CBA(9 million-10.9 million U), divided into two times (1/12h), for each time, 0.5-1 hour is needed to complete the infusion. Drug: colistin, other name: Colistimethate Sodium for Injection

Drug: treatment with or without colistin

control group

ACTIVE COMPARATOR

For patients in this group,best available treatment without colistin is used. Ceftazidime-avibactam, tigecycline combined with metroperan or imipenem（MIC≤8mg/L）, tigecycline combined with aminoglycosides (amikacin) are suggested to treat patients diagnosed with hospital-acquired pneumonia or bloodstream infection caused by carbapenem-resistant enterobacteriaceae.Dose of other drugs are listed below: 1-2g meropenem should be given every 8 hours，1g Imipenem every 8 hours or 6 hours，0.8g Amikacin everyday，2.5g ceftazidime-avibactam every 8 hours. A load dose of 200mg tigecycline is needed, followed by 100mg every 12 hours.

Drug: treatment with or without colistin

Interventions

treatment with or without colistin DRUG

For patients in this treatment group, colistin based therapy is used. Colistin combined with metroperan or imipenem（MIC≤8mg/L），or colistin combined with tigecycline, or colistin combined with aminoglycosides (amikacin) are suggested to treat patients diagnosed with hospital-acquired pneumonia or bloodstream infection caused by carbapenem-resistant enterobacteriaceae. For patients in the control, best available treatment without colistin is uesed; Ceftazidime-avibactam, tigecycline combined with metroperan or imipenem（MIC≤8mg/L）, tigecycline combined with aminoglycosides (amikacin) are suggested to treat patients diagnosed with hospital-acquired pneumonia or bloodstream infection caused by carbapenem-resistant enterobacteriaceae.

colistin group; control group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who can provide written informed consent or their informed consent can be provided by legal guardian
• Patients who are hospitalized
• Adults ≥18 years and ≤85 years of age
• 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.
• 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).
• Patients whose APACHE II score is between 10 and 30.

You may not qualify if:

• Patients who received polymyxin for more than 48 hours in the 72 hours prior to randomization.
• Patients who received antibiotics more than 24 hours in the 72 hours prior to randomization, and after treatment，conditions of patients improved.
• Patient with history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to Colistimethate Sodium for Injection or other ingredients of it.
• 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.
• 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.
• Patients with hematological malignancy such as leukemia, lymphoma and multiple myeloma.
• Patients with lung/heart transplantation or stem cell transplantation.
• 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.
• Patients with chronic liver failure with portal hypertension, acute hepatic failure or acute decompensation of chronic hepatic failure.
• Patients who participated in other clinical trials within three months.
• Patient was pregnant or breastfeeding. If either urine or serum β-hCG test was positive, the patient was excluded.
• Patient who have been previously enrolled in this study.
• Patients who have condionts that may affect the trial.
• Other conditions exist researchers thought are not suitable.

Sponsors & Collaborators

• Southeast University, China: lead

Study Sites (15)

Anhui Provincial People's Hospital

Hefei, Anhui, 230000, China

RECRUITING

The First Hospital of Anhui Medical University

Hefei, Anhui, 230000, China

RECRUITING

Jinjiang Municipal Hospitall

Jinjiang, Fujian, 362200, China

RECRUITING

Huai'an First People's Hospital

Huai'an, Jiangsu, 223000, China

RECRUITING

The First Hospital of Lianyungang

Lianyungang, Jiangsu, 222000, China

RECRUITING

Zhongda Hospital Affiliated to Southeast University

Nanjing, Jiangsu, 210000, China

RECRUITING

Affiliated Hospital of Nantong University

Nantong, Jiangsu, 226000, China

RECRUITING

Suzhou Municipal Hospitial

Suzhou, Jiangsu, 215000, China

RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

RECRUITING

JiangsuTaizhou People's Hospital

Taizhou, Jiangsu, 225300, China

RECRUITING

Wuxi No.2 People's Hospital

Wuxi, Jiangsu, 214000, China

RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, 221000, China

RECRUITING

Yancheng No.1 People's Hospital

Yancheng, Jiangsu, 224000, China

RECRUITING

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, 225000, China

RECRUITING

Yixing People's Hospital

Yixing, Jiangsu, 214000, China

RECRUITING

Related Publications (1)

• Li X, Zhang C, Li J, Chen T, Xie J, Huang Y. Multicentre open-label randomised controlled trial comparing the efficacy and safety of colistin-based combination therapy with the best available therapy for treating hospital-acquired pneumonia or bloodstream infections caused by carbapenem-resistant Enterobacteriaceae (COUNT-CRE): a study protocol. BMJ Open. 2025 Jul 16;15(7):e092157. doi: 10.1136/bmjopen-2024-092157.

  PMID: 40669898 DERIVED

MeSH Terms

Conditions

Healthcare-Associated Pneumonia; Sepsis

Interventions

Therapeutics; Colistin

Condition Hierarchy (Ancestors)

Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins

Study Officials

• Yingzi Huang, MD

  Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University

  STUDY CHAIR

Central Study Contacts

Yingzi Huang, MD

CONTACT

+86-025-83262552; yz_huang@126.com

Jianfeng Xie, MD

CONTACT

+86-025-83262552; xie820405@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 25, 2023
• Study Start: November 27, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (15)