A Clinical Trial for the Treatment of Carbapenem Resistant Gram-negative Bacterial Infection With Colistimethate Sodium for Injection

NCT06198764 | Recruiting Phase 3

• 1 other identifier: TQD3519-CS-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 32

Brief Summary

A clinical study to evaluate Colistimethate Sodium for Injection combination with Meropenem versus Coly-Mycin® M Parenteral combined with Meropenem in the treatment of Carbapenem resistant gram-negative bacteria infection. A total of 80 patients will be enrolled in the study.

Conditions

Mental Health Issue

Outcome Measures

Primary Outcomes (1)

• Clinical cure rate (mITT)

  The proportion of patients in the modified intention to treat (mITT) population who achieved clinical cure at test of cure (TOC).

  At TOC visit, which is 7-14 days after the end of treatment.

Secondary Outcomes (6)

• Bacterial clearance rate

  At TOC visit, which is 7-14 days after the end of treatment.

• Clinical cure rate

  At TOC visit, which is 7-14 days after the end of treatment.

• Microbiological efficacy

  At TOC visit, which is 7-14 days after the end of treatment.

• All-cause mortality rate

  28±2 days after randomization.

• Peak concentration (Cmax)

  72 hours before the first dose; 30 minutes before the first dose, at the end and 2, 4, 6, 8 hours after dose on day 4; 30 minutes before the second dose; 30 minutes before the first dose on day 10.

Study Arms (2)

Colistimethate sodium for Injection + Meropenem

EXPERIMENTAL

Intravenous infusion of colistimethate sodium for injection for 7-14 days. Meropenem intravenous infusion once every 8 hours or 12 hours.

Drug: Colistimethate sodium for injection; Drug: Meropenem for Injection

Coly-Mycin® M Parenteral + Meropenem

ACTIVE COMPARATOR

Intravenous infusion of Coly-Mycin® M Parenteral for 7-14 days. Meropenem intravenous infusion once every 8 hours or 12 hours.

Drug: Meropenem for Injection; Drug: Coly Mycin M Injectable Product

Interventions

Colistimethate sodium for injection DRUG

Colistimethate Sodium for Injection is the Prodrug of Polymyxin E, which is hydrolyzed into Polymyxin E after entering the human body to play a bactericidal role.Polymyxin selectively acts on gram-negative aerobic bacteria with hydrophobic outer membrane, leading to cell death by destroying the cell membrane.

Colistimethate sodium for Injection + Meropenem

Meropenem for Injection DRUG

Meropenem is a broad-spectrum carbapenem antibiotic that inhibits the synthesis of bacterial cell walls by penetrating the cell wall and reaching its target, the penicillin-binding protein, to ultimately produce antibacterial effects.

Colistimethate sodium for Injection + Meropenem; Coly-Mycin® M Parenteral + Meropenem

Coly Mycin M Injectable Product DRUG

Coly Mycin M is the originally marketed colistimethate sodium for injection.

Coly-Mycin® M Parenteral + Meropenem

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old (based on the signing time of the informed consent form).
• The subject (or their guardian) voluntarily signs an informed consent form.
• Cultivate a Gram negative bacterium identified as carbapenem resistant within 5 days before or during the screening period (mainly including carbapenem resistant Enterobacteriaceae, carbapenem resistant Acinetobacter baumannii, and carbapenem resistant Pseudomonas aeruginosa), and the Gram negative bacteria showed drug resistance to carbapenems in vitro drug sensitive test. In this study, gram-negative bacteria resistant to carbapenems also included strains with bacterial drug sensitivity displayed as "intermediate", that is, resistant bacteria include strains that are intermediate and resistant to carbapenem antibiotics.
• Within 72 hours before randomization, for those who have previously received empirical antimicrobial treatment, the duration of antimicrobial treatment (excluding polymyxin antibiotics) does not exceed 24 hours or the treatment exceed 48 hours but the infection symptoms/signs still exist or become worsen.
• HAP/VAP subjects are required to meet:
• Patients with acute pulmonary parenchymal infection who have been hospitalized for more than 48 hours or discharged for less than 7 days, or have received mechanical ventilation through oral or nasal tracheal intubation for at least 48 hours;
• Chest X-ray examination (or computed tomography) obtained within 72 hours before randomization shows new infiltrating lesions or progression of existing lesions;
• Individuals with at least 2 of the following clinical symptoms/signs:
• New occurrence cough；
• Produce purulent sputum or tracheal secretions；
• The auscultation results are accord with pneumonia/lung consolidation (such as wet rale, dry rale, bronchial breath sound, egophony, dull percussion note);
• Difficulty in breathing, shortness of breath (respiratory rate\>25 breaths/minute), or hypoxemia (oxygen saturation\< 90% when breathing indoor air at standard atmospheric pressure or arterial blood oxygen partial pressure (PaO2) obtained through arterial blood gas (ABG)\<60 mmHg);
• The oxygenation index (arterial partial pressure of oxygen/percentage of inhaled oxygen concentration (PaO2/FiO2)) deteriorates, requiring urgent changes in ventilator support status or changes in positive end expiratory pressure ventilation volume.
• Within 72 hours before the first dose of study drug, the subject is required to take appropriate respiratory specimens (such as sputum, respiratory secretions, culture samples, etc.)
• With at least one of the following evidence of systemic inflammatory reactions:

You may not qualify if:

• Individuals who currently have epilepsy/myasthenia gravis or have a history of seizures (excluding febrile seizures in childhood)/myasthenia gravis history.
• Individuals undergoing hemodialysis or peritoneal dialysis.
• Invasive aspergillosis, mucormycosis, or other invasive fungal diseases.
• Current patients complicated with other infections, including endocarditis, osteomyelitis, central nervous system infection (such as meningitis, brain abscess, infection after cerebrospinal fluid shunt or shunt device infection), artificial joint infection, and active tuberculosis.
• It is currently complicated with refractory septic shock, and there was still persistent hypotension after sufficient fluid resuscitation or pressure therapy before randomization.
• Evidence of obvious liver disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy.
• Individuals with immunodeficiency or low immune function, including but not limited to: human immunodeficiency virus infection, hematological malignancies, bone marrow transplantation, immunosuppressive therapy, systemic corticosteroid therapy (defined as a daily dose equivalent to prednisone ≥ 20 mg and a course of treatment\>14 days).
• Individuals with any laboratory test abnormalities during the screening period: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) are 5 times higher than the upper limit of normal, or AST and/or ALT are 3 times higher than the upper limit of normal and total bilirubin is 1.5 times higher than the upper limit of normal, or neutrophil count is less than 1.0× 10\^9/L or platelet count\<60 ×10\^9/L; Creatinine clearance rate ≤ 50 ml/min.
• According to the clinical judgment of the researchers, the expected survival period is less than 1 month.
• Individuals with allergic reactions to polymyxin or carbapenems.
• Subjects who require more than 2 systemic antibiotics for the treatment of Gram negative bacterial infections.
• Patients with acute physiology and chronic health (APACHE II) scores greater than 30.
• HAP/VAP subjects need to exclude:
• Patients with lung diseases that can interfere with treatment response evaluation, (such as cystic fibrosis, granulomatous diseases, pulmonary fungal infections, or recent pulmonary embolism);
• Individuals with lung abscess, empyema, or obstructive pneumonia;

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: lead

Study Sites (32)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233099, China

RECRUITING

The People's Hospital of Chizhou

Chizhou, Anhui, 247099, China

RECRUITING

Beijing You'an Hospital, Capital Medical University

Beijing, Beijing Municipality, 100069, China

RECRUITING

People's Hospital of Chongqing Banan District

Chongqing, Chongqing Municipality, 401320, China

RECRUITING

Chongqing University Jiangjin Hospital

Chongqing, Chongqing Municipality, 402260, China

RECRUITING

Zhongshan Hospital Xiamen University

Xiamen, Fujian, 361004, China

RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510260, China

RECRUITING

The First Affiliated Hospital of Shantou University School of Medicine

Shantou, Guangdong, 515041, China

RECRUITING

Luoyang Central Hospital

Luoyang, Henan, 471099, China

RECRUITING

Sanmenxia Central Hospital

Sanmenxia, Henan, 472099, China

RECRUITING

Xiangyang Central Hospital

Xiangyang, Hubei, 441021, China

RECRUITING

Hunan Provincial People's Hospital

Changsha, Hunan, 410002, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

RECRUITING

Changsha Central Hospital

Changsha, Hunan, 410028, China

RECRUITING

Huai'an Second People's Hospital

Huaian, Jiangsu, 223022, China

RECRUITING

General Hospital of the Eastern Theater Command

Nanjing, Jiangsu, 210002, China

RECRUITING

Taizhou Hospital of TCM

Taizhou, Jiangsu, 225399, China

RECRUITING

Jiangsu Subei People's Hospital

Yangzhou, Jiangsu, 225003, China

RECRUITING

The Second Norman Bethune Hospital of Jilin University

Changchun, Jilin, 130041, China

RECRUITING

The first hospital of Jilin University

Changchun, Jilin, 130061, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, 110002, China

RECRUITING

General Hospital of Northern Theater Command

Shenyang, Liaoning, 110031, China

RECRUITING

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Huadong Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Shanghai Jiading District Central Hospital

Shanghai, Shanghai Municipality, 201899, China

RECRUITING

Changzhi People's Hospital

Changzhi, Shanxi, 046099, China

RECRUITING

The First Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610044, China

RECRUITING

Tianjin Chest Hospital

Tianjin, Tianjin Municipality, 300222, China

ACTIVE NOT RECRUITING

The First Hospital of Xinjiang Medical University

Ürümqi, Xinjiang Uygur Autonomous Region, 830054, China

RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Interventions

colistinmethanesulfonic acid; Injections; Meropenem

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Yingyuan Zhang, Bachelor of Medicine

CONTACT

13917467481; yyzhang39@hotmail.com

Haihui Huang, Doctor

CONTACT

13916685836; Huanghaihui@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: January 10, 2024
• Study Start: July 6, 2023
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: January 10, 2024

Record last verified: 2023-12

Locations

CN (32)