Study on the Safety and Efficacy of Polymyxin E2 Methanesulfonate for Injection in the Treatment of Hospital-Acquired Bacterial Pneumonia/Ventilator-Associated Bacterial Pneumonia Caused by Carbapenem-Resistant Gram-Negative Bacteria

NCT07512596 | Not Yet Recruiting Phase 2

• 1 other identifier: TQD3524-II-02
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 27

Brief Summary

Study on the Safety and Efficacy of Polymyxin E2 Methanesulfonate for Injection in the Treatment of Hospital-Acquired Bacterial Pneumonia/Ventilator-Associated Bacterial Pneumonia Caused by Carbapenem-Resistant Gram-Negative Bacteria.

Conditions

Hospital-acquired Bacterial Pneumonia/Ventilator-associated Bacterial Pneumonia

Outcome Measures

Primary Outcomes (2)

• The proportion of subjects who achieved clinical cure

  The proportion of subjects who achieved clinical cure in the modified intention-to-treat (mITT) population at the treatment-end visit (TOC) based on clinical efficacy evaluation.

  Up to 28 days

• The percentage difference in subjects achieving clinical cure between the experimental group and the control group

  During the TOC visit, the percentage difference in subjects achieving clinical cure between the modified intention-to-treat (mITT) populations of the test group and the control group.

  Up to 28 days

Secondary Outcomes (10)

• The bacterial clearance rate

  Up to 28 days

• The proportion of subjects who achieved clinical cure

  Up to 21 days

• The proportion of subjects who achieved clinical cure

  Up to 21 days

• The proportion of subjects who achieved clinical cure

  Up to 28 days

• All-cause mortality

  Up to 28 days

Study Arms (4)

Low-dose TQD3524 + Meropenem for injection

EXPERIMENTAL

TQD3524: 2.5mg/kg, q12h, intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days TQD3524 : 70mg, q12h, nebulized inhalation, for a duration of 7 to 14 days, with a maximum of 21 days Meropenem for injection: 2g, q8h,intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days

Drug: TQD3524; Drug: Meropenem for injection

Colistimethate Sodium for Injection + Meropenem for injection (Low-dose control)

ACTIVE COMPARATOR

Colistimethate Sodium for Injection: 2.5mg/kg, q12h, intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days Colistimethate Sodium for Injection: 70mg, q12h, nebulized inhalation, for a duration of 7 to 14 days, with a maximum of 21 days Meropenem for injection: 2g, q8h,intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days

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

High-dose TQD3524 + Meropenem for injection

EXPERIMENTAL

TQD3524: 3.75mg/kg, q12h, intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days TQD3524 : 70mg, q12h, nebulized inhalation, for a duration of 7 to 14 days, with a maximum of 21 days Meropenem for injection: 2g, q8h,intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days

Drug: TQD3524; Drug: Meropenem for injection

Colistimethate Sodium for Injection + Meropenem for injection (High-dose control)

ACTIVE COMPARATOR

Colistimethate Sodium for Injection: 2.5mg/kg, q12h, intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days Colistimethate Sodium for Injection: 70mg, q12h, nebulized inhalation, for a duration of 7 to 14 days, with a maximum of 21 days Meropenem for injection: 2g, q8h,intravenous drip, for a duration of 7 to 14 days, with a maximum of 21 days

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

Interventions

TQD3524 DRUG

After entering the body, TQD3524 can be hydrolyzed into polymyxin E2 and its derivatives, exerting bactericidal effects .

High-dose TQD3524 + Meropenem for injection; Low-dose TQD3524 + Meropenem for injection

Meropenem for injection DRUG

Meropenem for injection is a β-lactam.

Colistimethate Sodium for Injection + Meropenem for injection (High-dose control); Colistimethate Sodium for Injection + Meropenem for injection (Low-dose control); High-dose TQD3524 + Meropenem for injection; Low-dose TQD3524 + Meropenem for injection

Colistimethate Sodium for Injection DRUG

Colistimethate Sodium for Injection is a prodrug of polymyxin E. After entering the body, polymyxin E mesylate is hydrolyzed to polymyxin E (colistin), which exerts bactericidal activity.

Colistimethate Sodium for Injection + Meropenem for injection (High-dose control); Colistimethate Sodium for Injection + Meropenem for injection (Low-dose control)

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 date of signing the informed consent form);
• The subject (or their guardian) voluntarily signed the informed consent form；
• Acute pulmonary infection with hospitalization duration exceeding 48 hours or within 7 days after discharge; or acute pulmonary infection patients who have undergone mechanical ventilation via oral or nasal tracheal intubation for at least 48 hours;
• Chest imaging examination (X-ray or CT) within 72 hours prior to randomization reveals characteristics of new or worsening pulmonary infiltration;
• At least one of the following physical signs or laboratory abnormalities: ① fever (temperature ≥38℃); ② hypothermia (temperature ≤35℃); ③ elevated peripheral white blood cell count (WBC ≥10×10\^9/L); ④ decreased white blood cell count (WBC ≤4.5×10\^9/L); ⑤ more than 15% of immature neutrophils such as band forms in peripheral blood;
• At least one of the following clinical symptoms is present: ① new or acute worsening of pulmonary symptoms or signs, such as cough, dyspnea, increased respiratory rate (respiratory rate \> 25 breaths per minute), expectoration, or the need for mechanical ventilation; ② hypoxemia (arterial blood gas oxygen partial pressure below 60 mmHg at standard atmospheric pressure, or a progressive decrease in the ratio of oxygen partial pressure to inspired oxygen concentration (PaO2/FiO2)); ③ deteriorating oxygenation requiring replacement of ventilation support system to improve oxygenation, or a change in the level of positive end-expiratory pressure support; ④ new respiratory secretions requiring suction;
• A specific carbapenem-resistant Gram-negative bacterium was cultured from qualified lower respiratory tract specimens within the first five days/screening period, with in vitro susceptibility testing confirming resistance to carbapenems；
• Female subjects without reproductive potential must meet at least one of the following criteria: a) cessation of regular menstruation for at least 12 consecutive months; b) having undergone hysterectomy and/or bilateral oophorectomy. Female subjects with reproductive potential must have a negative serum pregnancy test result at the screening visit and agree to use reliable contraception throughout the study period;
• Male subjects must agree to adopt reliable contraceptive measures throughout the entire study period.

You may not qualify if:

• Those who currently suffer from epilepsy/myasthenia gravis or have a history of seizures (excluding febrile seizures in childhood)/myasthenia gravis;
• Those who are undergoing hemodialysis or peritoneal dialysis;
• Combined infections with other lung microbiota: viral pneumonia, fungal pneumonia, pulmonary tuberculosis, atypical pathogen infections, etc；
• Current concurrent infection of other parts/organs;
• Patients with concurrent refractory septic shock, who still exhibit persistent hypotension despite adequate fluid resuscitation or vasopressor therapy prior to randomization;
• Individuals with immune deficiency or compromised immune function, including but not limited to: human immunodeficiency virus infection, hematological malignancies, bone marrow transplantation, immunosuppressive therapy, and systemic corticosteroid treatment (defined as a daily dose equivalent to prednisone ≥20mg and a treatment duration \>14 days);
• During the screening period, any of the following laboratory abnormalities is present: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels are more than 5 times the upper limit of normal, or AST and/or ALT levels are more than 3 times the upper limit of normal and total bilirubin levels are more than 1.5 times the upper limit of normal, or neutrophil count \< 1.0×10\^9/L, or platelet count \< 60×10\^9/L; creatinine clearance rate (cLcr) ≤ 50 mL/min;
• Suffering from lung diseases that can interfere with treatment response assessment;
• Patients with lung abscess, empyema, and mechanical obstructive pneumonia;
• New York Heart Association (NYHA) class III-IV heart failure;
• Transplant patients；
• Patients with an estimated survival time of less than 1 month according to the clinical judgment of the researchers;
• Individuals with allergic reactions to polymyxins or carbapenems;
• Sbjects requiring \>2 systemic antimicrobial drugs for the treatment of Gram-negative bacterial infections;
• Patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 30;

Sponsors & Collaborators

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

Study Sites (27)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233000, China

Location

Beijing Tsinghua Changgung Hospital

Beijing, Beijing Municipality, 102200, China

Location

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

Foshan Nanhai District People's Hospital

Foshan, Guangdong, 528200, China

Location

The First Clinical College of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

Location

The Fifth Affiliated Hospital, Sun Yat-sen University

Zhuhai, Guangdong, 519000, China

Location

The Second Hospital Of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

Location

Henan Provincial People's Hospital

Zhengzhou, Henan, 450003, China

Location

Zhengzhou Central Hospital

Zhengzhou, Henan, 450007, China

Location

The Fifth Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

The Second Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Xiangya Hospital of Central South University

Changsha, Hunan, 410000, China

Location

People's Hospital of Hunan Province

Changsha, Hunan, 410005, China

Location

The Third Hospital of Changsha

Changsha, Hunan, 410015, China

Location

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, 225000, China

Location

First Affiliated Hospital of Gannan Medical University

Ganzhou, Jiangxi, 341000, China

Location

The First Affiliated Hospital of Xi'an Jiao Tong University

Xi'an, Shaanxi, 710000, China

Location

Xi'an Chest Hospital

Xi'an, Shaanxi, 710100, China

Location

Yan'an University Xianyang Hospital

Xianyang, Shaanxi, 712000, China

Location

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Chengdu Third People's Hospital

Chengdu, Sichuan, 610031, China

Location

Nuclear Industry 416 Hospital

Chengdu, Sichuan, 610051, China

Location

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

Tianjin First Central Hospital

Tianjin, Tianjin Municipality, 300191, China

Location

MeSH Terms

Interventions

Meropenem; Injections; colistinmethanesulfonic acid

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Yanbin Liu, Doctor

CONTACT

18980601983; dr_liuyanbin@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2026
• First Posted: April 6, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 17, 2026

Record last verified: 2025-10

Locations

CN (27)