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

Ceftolozane/Tazobactam (MK-7625A) Plus Metronidazole Versus Meropenem for Participants With Complicated Intra-abdominal Infection (MK-7625A-015)

Sponsors

Lead sponsor: Merck Sharp & Dohme Corp.

Source Merck Sharp & Dohme Corp.
Brief Summary

This study aims to evaluate the efficacy of ceftolozane/tazobactam (MK-7625A) plus metronizazole versus meropenem in adults diagnosed with complicated intra-abdominal infection (cIAI). The primary hypothesis is ceftolozane/tazobactam plus metronizazole 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.

Overall Status Recruiting
Start Date March 20, 2019
Completion Date November 3, 2020
Primary Completion Date November 3, 2020
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Favorable clinical response at the TOC visit (CE population) Up to Day 30
Secondary Outcome
Measure Time Frame
Favorable clinical response at the EOT visit (ITT population) Day 4 up to Day 14
Favorable clinical response at the TOC visit (ITT population) Up to Day 30
Favorable clinical response at the EOT visit (CE population) Day 4 up to Day 14
Favorable microbiological response at the TOC visit (EME population) Up to Day 30
Pathogens achieving a favorable microbiological response at the TOC visit (EME population) Up to Day 30
Adverse Events Up to Day 30
Discontinuations of treatment Up to Day 14
Enrollment 268
Condition
Intervention

Intervention type: Drug

Intervention name: Ceftolozane/Tazobactam

Description: Ceftolozane 1000 mg / Tazobactam 500 mg by IV infusion every 8 hours for 4 to 14 days. Participants with CrCL of 30 to ≤ 50 mL/min will receive Ceftolozane 500 mg / Tazobactam 250 mg.

Arm group label: Ceftolozane/Tazobactam + Metronidazole

Other name: MK-7625A

Intervention type: Drug

Intervention name: Metronidazole

Description: Metronidazole 500 mg by IV infusion every 8 hours for 4 to 14 days.

Arm group label: Ceftolozane/Tazobactam + Metronidazole

Intervention type: Drug

Intervention name: Meropenem

Description: Meropenem 1000 mg by IV infusion every 8 hours for 4 to 14 days. Participants with CrCL of 30 to ≤ 50 mL/min will receive IV infusion every 12 hours.

Arm group label: Meropenem + Placebo

Intervention type: Drug

Intervention name: Placebo

Description: Saline by IV infusion every 8 hours for 4 to 14 days.

Arm group label: Meropenem + Placebo

Eligibility

Criteria:

Inclusion Criteria:

- 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; is not a woman of childbearing potential (WOCBP); and if WOCBP agrees to follow the contraceptive guidance during the treatment period, and for at least 30 days after the last dose of study medication

Exclusion Criteria:

- 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 betalactam, 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 betalactam antibacterial

- 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

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Medical Director Study Director Merck Sharp & Dohme Corp.
Overall Contact

Last name: Toll Free Number

Phone: 1-888-577-8839

Email: [email protected]

Location
facility status contact
Anhui Provincial Hospital ( Site 0033) | Hefei, Anhui, 230001, China Recruiting Study Coordinator +8613855168588
Navy General Hospital ( Site 0009) | Beijing, Beijing, 100048, China Recruiting Study Coordinator +8618600310222
Peking University Third Hospital ( Site 0002) | Beijing, Beijing, 100191, China Recruiting Study Coordinator +8613701080921
The First Affiliated Hospital of Guangzhou Medical University ( Site 0026) | Guangzhou, Guangdong, 510120, China Recruiting Study Coordinator +8613903070123
Southern Medical University Nanfang Hospital ( Site 0055) | Guangzhou, Guangdong, 510515, China Recruiting Study Coordinator +8613802771450
Hainan General Hospital ( Site 0042) | Haikou, Hainan, 570311, China Recruiting Study Coordinator +8618889765723
Baotou Central Hospital ( Site 0013) | Baotou, Inner Mongolia, 014040, China Recruiting Study Coordinator +8604726955473
The First People's Hospital of Changzhou ( Site 0054) | Changzhou, Jiangsu, 213000, China Recruiting Study Coordinator +8651968870835
Wuxi No.2 People's Hospital ( Site 0050) | Wuxi, Jiangsu, 214002, China Recruiting Study Coordinator +8651068563496
Wuxi People's Hospital ( Site 0020) | Wuxi, Jiangsu, 214023, China Recruiting Study Coordinator 862163240090
Subei People's Hospital ( Site 0046) | Yangzhou, Jiangsu, 200080, China Recruiting Study Coordinator 8651487373012
Affiliated Hospital of Jiangsu University ( Site 0049) | Zhenjiang, Jiangsu, 212000, China Recruiting Study Coordinator +8651185082272
The First Affiliated Hospital of Nanchang University ( Site 0029) | Nanchang, Jiangxi, 330006, China Recruiting Study Coordinator +8679188692748
The Second Affiliated Hospital of Nanchang University ( Site 0053) | Nanchang, Jiangxi, 330006, China Recruiting Study Coordinator +8613907008850
The Second Hospital of Jilin University ( Site 0048) | Changchun, Jilin, 130022, China Recruiting Study Coordinator +86043181136313
Liaocheng People s hospital ( Site 0014) | Liaocheng, Shandong, 252000, China Recruiting Study Coordinator +8613346256926
Zhongshan Hospital of Fudan University ( Site 0001) | Shanghai, Shanghai, 200032, China Recruiting Study Coordinator +862160267662
Shanghai General Hospital ( Site 0016) | Shanghai, Shanghai, 200080, China Recruiting Study Coordinator +862163240090
Central Hospital of Minhang District ( Site 0052) | Shanghai, Shanghai, 201100, China Recruiting Study Coordinator +8651185082272
Tianjin People's Hospital ( Site 0040) | Tianjin, Tianjin, 300121, China Recruiting Study Coordinator +8602227557550
The First Affiliated Hospital of Xinjiang Medical University ( Site 0034) | Urumqi, Xinjiang, 830054, China Recruiting Study Coordinator +8613699995676
The First Hospital of Kunming ( Site 0041) | Kunming, Yunnan, 650200, China Recruiting Study Coordinator +8615877991051
Taizhou Hospital of Zhejiang Province ( Site 0035) | Taizhou, Zhejiang, 317000, China Recruiting Study Coordinator +86057685199810
The 2nd Affiliated Hospital of Wenzhou Medical University ( Site 0051) | Wenzhou, Zhejiang, 325000, China Recruiting Study Coordinator +8657788002738
The First Affiliated Hospital of Wenzhou Medical University ( Site 0015) | Wenzhou, Zhejiang, 325000, China Recruiting Study Coordinator 13857771611
Location Countries

China

Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Ceftolozane/Tazobactam + Metronidazole

Arm group type: Experimental

Description: Ceftolozane 1000 mg / Tazobactam 500 mg; plus Metronidazole 500 mg by intravenous (IV) infusion every 8 hours for 4 to 14 days. Participants with creatinine clearance (CrCL) of 30 to ≤ 50 mL/min will receive Ceftolozane 500 mg / Tazobactam 250 mg.

Arm group label: Meropenem + Placebo

Arm group type: Active Comparator

Description: Meropenem 1000 mg; plus saline by IV infusion every 8 hours for 4 to 14 days. Participants with CrCL of 30 to ≤ 50 mL/min will receive meropenem by IV infusion every 12 hours.

Acronym 7625ACNPhase3
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov