Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
The study will be conducted in accordance with good clinical practice and with the guidelines set out in the Declaration of Helsinki. After approval from local and national ethics committees, patients diagnosed with Hospital-acquired-pneumonia (HAP)or bloodstream infection caused by CRE from 14 centres in China will be recruited. All patients will be randomized to receive treatment with or without colistin in the ICU. The purpose of this study is to investigate the efficacy and safety of colistin when used to treat patients with CRE infection. The primary outcome is 14-day all cause mortality and the second outcomes include 14-day clinical cure rate, 14-day efficacy rate, ICU free days within 28 days after randomization,14-day microbiological cure rate,incidence of adverse events and severe adverse events in first 14 days, hospital mortality, 28-day all cause mortality, ICU mortality. Clopper-Pearson method is used to calculate the 95% confidence interval of mortality, Miettinen and Nurminen method is used to detect the difference between the two groups.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 14-day clinical cure rate | the proportion of subjects who are thought as clinical effectiveness 14 days after randomization to the number of subjects in each group. | from randomization to day 14 |
| 14-day efficacy rate |
Not provided
Inclusion Criteria:
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.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yingzi Huang, MD | Contact | +86-025-83262552 | yz_huang@126.com | |
| Jianfeng Xie, MD | Contact | +86-025-83262552 | xie820405@126.com |
| Name | Affiliation | Role |
|---|---|---|
| Yingzi Huang, MD | Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anhui Provincial People's Hospital | Recruiting | Hefei | Anhui | 230000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40669898 | Derived | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
the proportion of subjects of who are thought as recovery 14 days after randomization to the number of subjects in each group.
| from randomization to day 14 |
| ICU free days within 28 days after randomization | days that patients are not treated in ICU within 28 days after randomization of each patient in each group. If the patient die within 28 days, it will be zero. | from randomization to day 28 |
| 14-day microbiological cure rate | the proportion of subjects of microbiological cure to the number of subjects in each group 14 days after randomization. | from randomization to day 14 |
| incidence of adverse events and severe adverse events within first 28 days | the proportion of patients who experience adverse events and severe adverse events within 14 days after randomization to the number of subjects in each group wihtin first 14 days | from randomization to day 28 |
| hospital mortality | the proportion of subjects who die when treated in hospital to the number of subjects in each group | to be evaluated up to 90 days post randomization |
| 28-day all cause mortality | the proportion of subjects who die within 28 days after randomization to the number of subjects in each group | from randomization to day 28 |
| ICU mortality | the proportion of subjects who die in ICU to the number of subjects in each group | to be evaluated up to 90 days post randomization |
| The First Hospital of Anhui Medical University | Recruiting | Hefei | Anhui | 230000 | China |
|
| Jinjiang Municipal Hospitall | Recruiting | Jinjiang | Fujian | 362200 | China |
|
| Huai'an First People's Hospital | Recruiting | Huai'an | Jiangsu | 223000 | China |
|
| The First Hospital of Lianyungang | Recruiting | Lianyungang | Jiangsu | 222000 | China |
|
| Zhongda Hospital Affiliated to Southeast University | Recruiting | Nanjing | Jiangsu | 210000 | China |
|
| Affiliated Hospital of Nantong University | Recruiting | Nantong | Jiangsu | 226000 | China |
|
| Suzhou Municipal Hospitial | Recruiting | Suzhou | Jiangsu | 215000 | China |
|
| The First Affiliated Hospital of Soochow University | Recruiting | Suzhou | Jiangsu | 215000 | China |
|
| JiangsuTaizhou People's Hospital | Recruiting | Taizhou | Jiangsu | 225300 | China |
|
| Wuxi No.2 People's Hospital | Recruiting | Wuxi | Jiangsu | 214000 | China |
|
| Xuzhou Central Hospital | Recruiting | Xuzhou | Jiangsu | 221000 | China |
|
| Yancheng No.1 People's Hospital | Recruiting | Yancheng | Jiangsu | 224000 | China |
|
| Northern Jiangsu People's Hospital | Recruiting | Yangzhou | Jiangsu | 225000 | China |
|
| Yixing People's Hospital | Recruiting | Yixing | Jiangsu | 214000 | China |
|
| ID | Term |
|---|---|
| D000077299 | Healthcare-Associated Pneumonia |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D003428 | Cross Infection |
| D007239 | Infections |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
Not provided
Not provided
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D003091 | Colistin |
| ID | Term |
|---|---|
| D011113 | Polymyxins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D055666 | Lipopeptides |
| D008055 | Lipids |
| D023181 | Antimicrobial Cationic Peptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000089882 | Antimicrobial Peptides |
| D052899 | Pore Forming Cytotoxic Proteins |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
Not provided
Not provided