- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06051513
Efficacy and Safety of Colistimethate Sodium for Injection in The Treatment of Carbapenem-Resistant Enterobacteriaceae Infection
Colistimethate Sodium for Injection in The Treatment of Carbapenem-Resistant Enterobacteriaceae Infection:a Prospective, Open-label, Randomized Controlled, Multicenter Clinical Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Yingzi Huang, MD
- Phone Number: +86-025-83262552
- Email: yz_huang@126.com
Study Contact Backup
- Name: Jianfeng Xie, MD
- Phone Number: +86-025-83262552
- Email: xie820405@126.com
Study Locations
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Anhui
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Hefei, Anhui, China, 230000
- Recruiting
- Anhui Provincial People's Hospital
-
Contact:
- Aijun, Pan
- Phone Number: +8613866668786
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Hefei, Anhui, China, 230000
- Recruiting
- The First Hospital of Anhui Medical University
-
Contact:
- Min Shao
- Phone Number: +8615656065677
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Fujian
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Jinjiang, Fujian, China, 362200
- Recruiting
- Jinjiang Municipal Hospitall
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Contact:
- Sen Lin
- Phone Number: +8618065956302
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Jiangsu
-
Huai'an, Jiangsu, China, 223000
- Recruiting
- Huai'an First People's Hospital
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Contact:
- Xiangcheng Zhang
- Phone Number: +8615896169171
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Lianyungang, Jiangsu, China, 222000
- Recruiting
- The First Hospital of Lianyungang
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Contact:
- Suxia Liu
- Phone Number: +8618961326708
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Nanjing, Jiangsu, China, 210000
- Recruiting
- Zhongda Hospital Affiliated to Southeast University
-
Contact:
- Yingzi Huang
- Phone Number: +86-25-83262552
- Email: yz_huang@126.com
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Nantong, Jiangsu, China, 226000
- Recruiting
- Affiliated Hospital Of Nantong University
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Contact:
- Hongsheng Zhao
- Phone Number: +8613962918910
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Suzhou, Jiangsu, China, 215000
- Recruiting
- The First Affiliated Hospital of Soochow University
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Contact:
- Jun Jin
- Phone Number: +8613806214010
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Taizhou, Jiangsu, China, 225300
- Recruiting
- JiangsuTaizhou People's Hospital
-
Contact:
- Jilu Ye
- Phone Number: +8613852609309
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Wuxi, Jiangsu, China, 214000
- Recruiting
- Wuxi No.2 People's Hospital
-
Contact:
- Liang Luo
- Phone Number: +8615961790376
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Xuzhou, Jiangsu, China, 221000
- Recruiting
- Xuzhou Central Hospital
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Contact:
- Jiaqiong Li
- Phone Number: +8618952170393
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Yancheng, Jiangsu, China, 224000
- Recruiting
- Yancheng No.1 People's Hospital
-
Contact:
- Genghua Mu
- Phone Number: +8613815584925
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Yangzhou, Jiangsu, China, 225000
- Recruiting
- Northern Jiangsu People's Hospital
-
Contact:
- Ruiqiang Zheng
- Phone Number: +8613952721411
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Yixing, Jiangsu, China, 214000
- Recruiting
- Yixing People's Hospital
-
Contact:
- Junjie Lu
- Phone Number: +8613606157979
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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 ≤90 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 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.
- 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).
- Patients whose APACHE II score is between 10 and 30.
Exclusion Criteria:
- Patients who received polymyxin 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 CKD receiving haemodialysis or peritoneal dialysis.
- Patients with an estimated creatinine clearance (CrCL) <16 mL/min when randomization is conducted.
- Patients expected to require haemodialysis or other renal support while on study therapy.
- Patients with chronic liver failure with portal hypertension, acute hepatic failure or acute decompensation of chronic hepatic failure.
- Patient had past or current history of epilepsy or seizure disorders, excluding febrile seizures of childhood.
- 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.
- Other conditions exist researchers thought are not suitable.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: colistin group
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 |
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.
|
Active Comparator: control group
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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
14-day all cause mortality
Time Frame: from randomization to day 14
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
14-day clinical cure rate
Time Frame: from randomization to day 14
|
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
Time Frame: from randomization to day 14
|
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
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ICU free days within 28 days after randomization
Time Frame: from randomization to day 28
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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
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14-day microbiological cure rate
Time Frame: from randomization to day 14
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the proportion of subjects of microbiological cure to the number of subjects in each group 14 days after randomization.
|
from randomization to day 14
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hospital mortality
Time Frame: to be evaluated up to 90 days post randomization
|
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
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28-day all cause mortality
Time Frame: from randomization to day 28
|
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
Time Frame: to be evaluated up to 90 days post randomization
|
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
|
incidence of adverse events and severe adverse events in first 28 days
Time Frame: from randomization to day 28
|
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 in first 14 days
|
from randomization to day 28
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Yingzi Huang, MD, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- COUNT-CRE
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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