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Intra-abdominal InfectionPhase 3NCT02739997

Study of Ceftolozane/Tazobactam (MK-7625A) in Combination With Metronidazole in Japanese Participants With Complicated Intra-abdominal Infection (MK-7625A-013)

A Phase 3 study testing MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) and metronidazole 500 mg in people with Intra-abdominal Infection and Complicated Intra-abdominal Infection, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 3, multi-site, non-randomized, open-label study evaluating the safety and efficacy of MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) plus metronidazole 500 mg for the treatment of Complicated Intra-abdominal Infections (cIAI) in Japanese participants. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) and metronidazole 500 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
No sites listed yet
Study dates
8 Apr 2016to 28 Jul 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has one of the following diagnoses with evidence of intra-peritoneal infection: cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall; diverticular disease with perforation or abscess; appendiceal perforation or periappendiceal abscess; acute gastric or duodenal perforation, traumatic perforation of the intestine; peritonitis due to perforated viscus or following a prior operative procedure; or Intra-abdominal abscess (including liver and spleen).
  • Has evidence of systemic infection
  • Had or has plans to have surgical intervention within 24 hours of the first dose of study drug
  • Has radiographic evidence of perforation or abscess if enrolled preoperatively
  • Is able to have intra-abdominal specimen taken at baseline for the microbiological assessment
  • Female participants of child bearing potential must not be pregnant (negative human chorionic gonadotropin test) or breastfeeding and must agree to use adequate contraception for the duration of the study and up to 35 days after the last dose of study drug
  • Male participants must agree to use adequate contraception for the duration of the study and up to 75 days after the last dose of study drug

Who cannot join

  • Has simple appendicitis; abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites; acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess; infectious mononucleosis; cystic fibrosis; or pelvic infections
  • Has complicated intra-abdominal infection managed by staged abdominal repair (STAR) or open abdomen drainage
  • Has had acute gastric or duodenal perforation (≤ 24 hours after) or traumatic perforation of the intestine (≤ 12 hours after) operated on after the perforation occurred
  • Is expected to be cured by only surgical intervention without use of systemic antibacterial therapy
  • Has used systemic antibacterial therapy for intra-abdominal infection for more than 24 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy
  • Has severe impairment of renal function (estimated CrCl < 30 mL/minute), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/hour urine output over 24 hours)
Show all 18Show fewer
  • Has a concomitant infection at the time of randomization, which requires non-study systemic antibacterial therapy in addition to study drug with the exception of an antibacterial with Gram-positive activity only (vancomycin, teicoplanin, linezolid and daptomycin)
  • Has used any postoperative non-study antibacterial therapy if enrolled preoperatively
  • Has used more than 1 dose of non-study antibacterial therapy following surgery if enrolled postoperatively
  • Has hepatic disease
  • Is unlikely to survive the 4 to 5 week study period
  • Has organic brain or spinal cord disease
  • Has any rapidly-progressing disease or immediately life-threatening illness
  • Has an immunocompromising condition (i.e., AIDS, hematological malignancy, or bone marrow transplantation, or immunosuppressive therapy) or is receiving ≥ 40 mg of prednisone per day administered continuously for > 14 days prior to study start
  • Has a history of any moderate or severe hypersensitivity or allergic reaction to any beta-lactam (β-lactam) antibacterial, including cephalosporins, carbapenems, penicillins, or β-lactamase inhibitors, or metronidazole, or nitroimidazole derivatives
  • Is receiving or has received disulfiram within 14 days before receiving study drug or who is currently receiving probenecid
  • Has participated in any clinical study of an investigational product within 30 days prior to the first dose of study drug
  • Has previously participated in any study of ceftolozane or MK-7625A.

About this study

Official title: A Multicenter, Open-label, Noncomparative, Japanese Phase III Study to Assess the Efficacy and Safety of Ceftolozane/Tazobactam (MK-7625A) Used in Combination With Metronidazole in Japanese Patients With Complicated Intra-abdominal Infection.

This is a Phase 3, multi-site, non-randomized, open-label study evaluating the safety and efficacy of MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) plus metronidazole 500 mg for the treatment of Complicated Intra-abdominal Infections (cIAI) in Japanese participants. Efficacy will be primarily assessed by clinical response defined as complete resolution or significant improvement in signs and symptoms of the index infection.

Being tested
MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g), metronidazole 500 mg
Medical subject headings
Intraabdominal Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g)Drug

    MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) administered as an intravenous (IV) infusion

  • metronidazole 500 mgDrug

    metronidazole 500 mg administered as an IV infusion

Study groups in NCT02739997
Study groupRoleWhat they receive
MK-7625A + metronidazoleExperimentalMK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days. The dose may be reduced to 750 mg (ceftolozane 500 mg/tazobactam 250 mg) for participants with a creatinine clearance (CrCl) of 30-50 mL/min.
Receives: Drug: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g); Drug: metronidazole 500 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Test of Cure (TOC)

    The percentage of participants with clinical responses (cure, failure, or indeterminate) at TOC was determined. Clinical cure 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". Clinical failure 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". Indeterminate was defined as "study data are not available for evaluation for any reason, including death during the study period unrelated to the index infection; or extenuating circumstances that preclude classification as cure or failure".

    Measured: Day 28 (28 days after initiating study therapy)

  2. Percentage of Participants With Adverse Events (AEs)

    The percentage of participants with ≥1 AEs was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measured: Up to Day 42 (up to 28 days after completing study therapy)

  3. Percentage of Participants Discontinuing Study Drug Due to AEs

    The percentage of participants withdrawing from study therapy due to an AE was determined.

    Measured: Up to Day 14

Secondary outcomes (6)
  1. Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at End Of Therapy (EOT)

    The percentage of participants with clinical responses (cure, failure, or indeterminate) at EOT was determined. Clinical cure 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". Clinical failure 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". Indeterminate was defined as "study data are not available for evaluation for any reason, including death during the study period unrelated to the index infection; or extenuating circumstances that preclude classification as cure or failure".

    Measured: Up to Day 14

  2. Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Late Follow-Up (LFU)

    The percentage of participants with clinical responses (cure, failure, or indeterminate) at LFU was determined. Clinical cure 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". Clinical failure 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". Indeterminate was defined as "study data are not available for evaluation for any reason, including death during the study period unrelated to the index infection; or extenuating circumstances that preclude classification as cure or failure".

    Measured: Up to Day 42 (28 days after completing study therapy)

  3. Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) at EOT

    The percentage of participants with microbiological responses (eradication, persistence, or indeterminate) at EOT was determined. Eradication was defined as "absence of the baseline pathogen in a specimen". Persistence was defined as "presence of the baseline pathogen in a specimen". Indeterminate was defined as "Baseline culture either not obtained or has an assessment of no growth, or any other circumstance that makes it impossible to define the microbiological response".

    Measured: Up to Day 14

  4. Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) at TOC

    The percentage of participants with microbiological response (eradication, persistence, or indeterminate) at TOC was determined. Eradication was defined as "absence of the baseline pathogen in a specimen". Persistence was defined as "presence of the baseline pathogen in a specimen". Indeterminate was defined as "Baseline culture either not obtained or has an assessment of no growth, or any other circumstance that makes it impossible to define the microbiological response".

    Measured: Day 28 (28 days after initiating study therapy)

  5. Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) by Pathogen at EOT

    The percentage of participants with per-pathogen microbiological responses at EOT was determined. Individual pathogens were identified at baseline, and the overall percentage of participants with eradication or presumed eradication within each pathogen category are shown.

    Measured: Up to Day 14

  6. Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) by Pathogen at TOC

    The percentage of participants with per-pathogen microbiological responses at TOC was determined. Individual pathogens were identified at baseline, and the overall percentage of participants with eradication or presumed eradication within each pathogen category are shown.

    Measured: Day 28 (28 days after initiating study therapy)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2016 (estimated)
  2. Study start8 Apr 2016
  3. Primary completion28 Jul 2017
  4. Study completion28 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02739997
Sponsor's protocol ID
7625A-013
Other IDs
MK-7625A-013, 163275
Status last verified
Jul 2018
First submitted
30 Mar 2016
Last updated
9 Aug 2018
Data monitoring committee
No
Individual data sharing
Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Li Z, Kang Y, Gao H, Zhao Y, Luo D, Wang D, Zhang X, Yu J, Chu G, Cao J, Wang F, Zhao X, Jensen E, Lin G, Chen G. Pooled data from phase 3 clinical trials comparing the clinical activity of ceftolozane/tazobactam versus meropenem for the treatment of complicated intra-abdominal infections. Infect Dis (Lond). 2026 Jan;58(1):40-51. doi: 10.1080/23744235.2025.2544828. Epub 2025 Sep 6.

    PubMed 40913503
  • Mikamo H, Monden K, Miyasaka Y, Horiuchi T, Fujimoto G, Fukuhara T, Yoshinari T, Rhee EG, Shizuya T. The efficacy and safety of tazobactam/ceftolozane in combination with metronidazole in Japanese patients with complicated intra-abdominal infections. J Infect Chemother. 2019 Feb;25(2):111-116. doi: 10.1016/j.jiac.2018.10.012. Epub 2018 Dec 6.

    PubMed 30528561

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) and metronidazole 500 mg in people with Intra-abdominal Infection and Complicated Intra-abdominal Infection, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Test of Cure (TOC) (time frame: Day 28 (28 days after initiating study therapy)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02739997, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2018.

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