A Phase 3, Multicenter, Double-blind, Randomized, Active-controlled Clinical Study to Evaluate the Efficacy and Safety of Ceftolozane/Tazobactam (MK-7625A) Plus Metronidazole Versus Meropenem in Chinese Participants With Complicated Intra-abdominal Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 268
- 试验地点
- 25
- 主要终点
- Percentage of Participants With Clinical Response (Clinical Cure or Clinical Failure) at Test of Cure (TOC) Visit: Clinically Evaluable (CE) Population
研究概览
简要总结
This study aims to evaluate the efficacy of ceftolozane/tazobactam (MK-7625A) plus metronidazole versus meropenem in adults diagnosed with complicated intra-abdominal infection (cIAI). The primary hypothesis is ceftolozane/tazobactam plus metronidazole is non-inferior to meropenem, as measured by the clinical response rate at the Test-of Cure (TOC) visit in the Clinically Evaluable (CE) population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have one of the following diagnoses in which there is evidence of bacterial intraperitoneal infection: Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall; Acute gastric or small intestine including duodenal perforation, only if operated on > 24 hours after perforation occurs; Traumatic perforation of the intestine (including colon), only if operated on > 12 hours after perforation occurs; Appendiceal perforation or peri-appendiceal abscess; Diverticular disease with perforation or abscess; Peritonitis due to other perforated viscus or following a prior operative procedure; Intra-abdominal abscess (including liver or spleen).
- •Evidence of systemic infection
- •Requires surgical intervention (e.g., laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of (before or after) the first dose of study drug
- •If participant is to be enrolled preoperatively, the participant should have radiographic evidence of gastric or bowel perforation or intra-abdominal abscess or other radiographic evidence for cIAI
- •Participants who failed prior antibacterial treatment for the current cIAI can be enrolled but must: (a) have a positive culture (from an intra-abdominal site or blood sample) and (b) require surgical intervention.
- •Is a Chinese participant, defined as a person of Chinese descent. A potential participant who is of ex-China descent (e.g. Western European) descent living in China will be excluded
- •Male agrees to use contraception during the treatment period, and for at least 30 days after the last dose of study medication, and refrain from donating sperm during this period
- •Female is not pregnant or breastfeeding; is not a woman of childbearing potential (WOCBP); or if WOCBP agrees to use a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period, and for at least 30 days after the last dose of study medication; or must have a negative highly sensitive pregnancy test (serum) within 48 hours before the first dose of study intervention.
排除标准
- •Has any of the following diagnoses: simple appendicitis; abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; spontaneous (primary) bacterial peritonitis associated with cirrhosis and chronic ascites; or pelvic infections
- •Has any of the following diseases: acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess
- •Has complicated intra-abdominal infection managed by staged abdominal repair (STAR), open abdomen technique (i.e. fascia not closed) including temporary closure of the abdomen, or any situation where infection source control was not likely to be achieved
- •Has abscess that is confirmed on imaging test but has not been or cannot be managed by surgical intervention including drainage
- •Is expected to be cured by only surgical intervention (e.g., drainage) without use of systemic antibiotic therapy
- •Has the following underlying conditions or the following serious conditions: considered unlikely to survive during the study period (predicted life expectancy is < 4 weeks after randomization); organic brain or spinal cord disease; any rapidly-progressing disease or immediately life-threatening illness (including respiratory failure and septic shock); an immunocompromising condition
- •Has a history of any hypersensitivity or allergic reaction to any beta-lactam, antibacterials, including cephalosporins, carbapenems, penicillins, or tazobactam, or metronidazole, or nitroimidazole derivatives; or if a skin test is required by local clinical regulations, has a positive skin test result if no prior history of allergic reaction to beta-lactam antibacterials
- •A WOCBP who has a positive serum pregnancy test within 24 hours before the first dose of study intervention
- •Used systemic antibiotic therapy with known coverage of pathogens that cause IAI for more than 24 hours during the previous 72 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy
- •For participants that are enrolled postoperatively, more than 1 dose of an active non-study antibacterial regimen administered postoperatively. For participants enrolled preoperatively, no postoperative non-study antibacterial therapy is allowed
- •Participants who need additional non-study systemic antibacterial therapy with gram-negative activity in addition to study drug therapy; drugs with only gram-positive activity (eg, IV vancomycin, teicoplanin, linezolid and daptomycin) are allowed
- •Anticipates treatment with traditional Chinese medicine or herbal medicine during study period
- •Has received disulfiram, valproic acid or divalproex sodium within 14 days before the proposed first day of study drug or who are currently receiving probenecid
- •Is currently participating in, or has participated in, any other clinical study involving the administration of investigational or experimental medication (not licensed by regulatory agencies) at the time of the presentation or during the previous 90 days prior to screening or is anticipated to participate in such a clinical study during the course of this study
- •Has participated in a ceftolozane/tazobactam clinical study at any time in the past
- •Has severe impairment of renal function (CrCL <30 mL/min) or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria
研究组 & 干预措施
Ceftolozane/Tazobactam + Metronidazole
Participants receive ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam may be adjusted to 500 mg/250 mg if creatinine clearance [CrCL] is 30 to ≤50 mL/min)
干预措施: Ceftolozane/Tazobactam (Drug)
Ceftolozane/Tazobactam + Metronidazole
Participants receive ceftolozane/tazobactam 1500 mg (ceftolozane 1000 mg + tazobactam 500 mg) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days (per protocol, ceftolozane/tazobactam may be adjusted to 500 mg/250 mg if creatinine clearance [CrCL] is 30 to ≤50 mL/min)
干预措施: Metronidazole (Drug)
Meropenem + Placebo
Participants receive meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem may be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
干预措施: Meropenem (Drug)
Meropenem + Placebo
Participants receive meropenem 1000 mg plus saline administered as an IV infusion every 8 hours for 4 to 14 days (per protocol, meropenem may be adjusted to every 12 hours if CrCL was 30 to ≤50 mL/min).
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Clinical Response (Clinical Cure or Clinical Failure) at Test of Cure (TOC) Visit: Clinically Evaluable (CE) Population
时间窗: Up to approximately Day 30
Clinical response was classified as "cure" or "failure". Clinical cure (favorable) was defined as complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure is required for the index infection. Clinical failure (unfavorable) was defined as death related to IAI at any time point; persisting or recurrent infection within the abdomen requiring additional intervention to cure; need for treatment with additional antibiotics for ongoing IAI symptoms; or post-surgical wound infection that requires additional antimicrobial therapy and/or non-routing wound care. The percentage of participants with clinical response of clinical cure or clinical failure at TOC was summarized.
次要结局
- Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at EOT Visit: ITT Population(Up to approximately Day 15)
- Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at TOC Visit: Intent to Treat (ITT) Population(Up to approximately Day 30)
- Percentage of Participants With Clinical Response (Clinical Cure or Clinical Failure) at End of Therapy (EOT) Visit: CE Population(Up to approximately Day 15)
- Percentage of Participants With Favorable Per-Participant Microbiological Response of Eradication or Presumed Eradication at TOC Visit: Expanded Microbiologically Evaluable (EME) Population(Up to approximately Day 30)
- Percentage of Participants With Favorable Microbiological Response of Eradication or Presumed Eradication, by Pathogen, at the TOC Visit: EME Population(Up to approximately Day 30)
- Percentage of Participants Who Experienced 1 or More Adverse Events (AEs)(Up to approximately Day 30)
- Percentage of Participants That Discontinued Study Treatment Due to an AE(Up to Day 14)