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

Официальное название

Randomized, Double-blind, Parallel-controlled, Multicenter Phase II Clinical Study to Evaluate the Efficacy and Safety of Polymyxin E2 Mesylate Intravenous Infusion Combined With Nebulized Inhalation in the Treatment of Hospital-acquired Bacterial Pneumonia/Ventilator-associated Bacterial Pneumonia Caused by Carbapenem-resistant Gram-negative Bacteria

Обзор

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.

Вмешательства

• Препарат TQD3524
  After entering the body, TQD3524 can be hydrolyzed into polymyxin E2 and its derivatives, exerting bactericidal effects .
• Препарат Meropenem for injection
  Meropenem for injection is a β-lactam.
• Препарат Colistimethate Sodium for Injection
  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.

Первичные конечные точки

• The proportion of subjects who achieved clinical cure [Срок оценки: Up to 28 days]
• The percentage difference in subjects achieving clinical cure between the experimental group and the control group [Срок оценки: Up to 28 days]

Вторичные конечные точки (10)

• The bacterial clearance rate [Срок оценки: Up to 28 days]
• The proportion of subjects who achieved clinical cure [Срок оценки: Up to 21 days]
• The proportion of subjects who achieved clinical cure [Срок оценки: Up to 21 days]
• The proportion of subjects who achieved clinical cure [Срок оценки: Up to 28 days]
• All-cause mortality [Срок оценки: Up to 28 days]
• Average duration of mechanical ventilation [Срок оценки: Up to 28 days]
• Average length of hospital stay [Срок оценки: Up to 28 days]
• Change in APACHE II score [Срок оценки: Up to 28 days]
• Change value of procalcitonin [Срок оценки: Up to 28 days]
• The proportion of patients experiencing adverse reactions [Срок оценки: Up to 28 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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;
• Women who are pregnant or breastfeeding;
• Use potentially effective antibiotics to treat carbapenem resistant gram-negative bacterial infections within 72 hours prior to randomization, and the treatment duration exceeds 24 hours；
• When the culture results of samples from the first 5 days/screening period are available, it is found that the subject has Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia (HAP/VAP) caused by gram-negative bacteria that are expected to have no response to polymyxin drugs;
• Subjects who have participated in other clinical trials within 30 days prior to the first dose of medication;
• Other factors determined by the researcher that make the subject unsuitable for participating in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 27 центров

• The First Affiliated Hospital of Bengbu Medical College — Bengbu
• Beijing Tsinghua Changgung Hospital — Пекин
• The First Affiliated Hospital of Chongqing Medical University — Чунцин
• Foshan Nanhai District People's Hospital — Foshan
• The First Clinical College of Guangzhou Medical University — Гуанчжоу
• Peking University Shenzhen Hospital — Шэньчжэнь
• The Fifth Affiliated Hospital, Sun Yat-sen University — Zhuhai
• The Second Hospital Of Hebei Medical University — Shijiazhuang
• … и ещё 19 центров

Идентификаторы

NCT: NCT07512596 · TQD3524-II-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗