Complicated Intra-abdominal InfectionPhase 2NCT01147640
Safety and Efficacy Study to Compare IV CXA 101/Tazobactam and Metronidazole With Meropenem in Complicated Intraabdominal Infections
A Phase 2 study testing CXA-101/ tazobactam and metronidazole in people with Complicated Intra-abdominal Infection, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 33 sites in 5 countries.
Trial summary
A Phase 2, multicenter, prospective, randomized, double-blind study of CXA-101/ tazobactam (1000/500 mg q8h) and metronidazole (500 mg q8h) IV infusion vs. meropenem IV infusion (1000 mg q8h) and a matching saline placebo (q8h) in the treatment of cIAI in adult subjects. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Complicated Intra-abdominal Infection
- What is being tested?
- CXA-101/ tazobactam and metronidazole
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 33 sitesin 5 countries
- Study dates
- 25 Jun 2010to 25 Mar 2011
- Phase
- Phase 2
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, from 18 to 90 years of age, inclusive
- One of the following diagnoses (in which there is evidence of intraperitoneal infection) including:(a) Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall;(b)Diverticular disease with perforation or abscess; (c) Appendiceal perforation or periappendiceal abscess; (d) Acute gastric or duodenal perforation, only if operated on >24 hours after perforation occurs; (e) Traumatic perforation of the intestine, only if operated on > 12 hours after perforation occurs; (f) Peritonitis due to perforated viscus, postoperative or spread from other focus of infection (but not spontaneous [primary] bacterial peritonitis or peritonitis associated with cirrhosis and chronic ascites).Subjects with inflammatory bowel disease or ischemic bowel disease are eligible provided there is bowel perforation; or (g) Intraabdominal abscess (including liver and spleen).
- Subject 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 subject is to be enrolled preoperatively, the subject must have radiographic evidence of bowel perforation or intraabdominal abscess
- Subjects who failed prior antibacterial treatment for the current cIAI can be enrolled but must: (a) have a positive culture (from an intraabdominal site) and (b) require surgical intervention. Such subjects can be enrolled before the results of the culture are known; however, if the culture is negative, study drug administration must be discontinued.
- Willing and able to comply with all study procedures and restrictions
- Willing and able to provide written informed consent
Who cannot join
- Women who are pregnant, nursing, or - if of child bearing potential - not using a medically accepted, effective method of birth control (e.g. condom, oral contraceptive, indwelling intrauterine device, or sexual abstinence)
- Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours; perforation of gastroduodenal ulcer with surgery within 24 hours (these are considered situations of peritoneal soiling before infection has become established); another intraabdominal process in which the primary etiology is not likely to be infectious.
- Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected, necrotizing pancreatitis, or pancreatic abscess
- cIAI managed by staged abdominal repair (STAR), open abdomen technique or any situation where infection source control is not likely to be achieved
- Known prior to randomization to have an IAI or postoperative infection caused by pathogen(s) resistant to meropenem
- Considered unlikely to survive the 4- to 5-week study period
Show all 24Show fewer
- Any rapidly-progressing disease or immediately life-threatening illness (including acute hepatic failure, respiratory failure and septic shock)
- The need for concomitant systemic antibacterial agents (other than vancomycin or linezolid) in addition to study drug(s)
- Moderate or severe impairment of renal function (estimated CrCl < 50 mL/min), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours)
- The presence of hepatic disease defined as: (a) ALT or AST > 4 x ULN; (b)Total bilirubin >2 x ULN, unrelated to cholecystitis (c) Alkaline phosphatase >4 x ULN. Subjects with a value >4 x ULN and <5 x ULN are eligible if this value is historically stable.
- Subjects with acute hepatic failure or acute decompensation of chronic hepatic failure
- Hematocrit < 25% or hemoglobin < 8 gm/dL
- Neutropenia with absolute neutrophil count < 1000/mm3
- Platelet count < 75,000 /mm3. Subjects with a platelet count as low as 50,000 /mm3 are permitted if the reduction is historically stable.
- Immunocompromising illness, including known human immunodeficiency virus (HIV) positivity or AIDS, organ (including bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroid therapy (e.g. >40 mg prednisone or equivalent per day for greater than 2 weeks).
- History of hypersensitivity reactions to cephalosporins, carbapenems, penicillins, ß-lactamase inhibitors, metronidazole, or nitroimidazole derivatives. Subjects with a history of mild skin rash, not documented to be caused by previous ß-lactam use, may be enrolled.
- Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of study data
- Clinically significant abnormality in baseline electrocardiogram (ECG)
- Participation in any investigational drug or device study within 30 days prior to study entry
- Use of systemic antibiotic therapy for IAI for 24 or more hours in the 48-hour period prior to the first dose of study drug, unless there is a documented treatment failure with such therapy
- More than one dose of an active non-study antibacterial regimen was given postoperatively. For subjects enrolled preoperatively, no postoperative non-study antibacterial therapy is allowed
- who previously participated in a study with CXA-101
- Subjects who previously received imipenem, meropenem, doripenem or cefepime for the current intraabdominal infection
- Subjects who have received disulfiram in the past 14 days or who are currently receiving probenecid.
Trial locations and contacts
33 sites in 5 countries.
33 sites in 5 countries
United States11 sites
University of Colorado Hospital
Aurora, Colorado, 88045
Metro Health Medical Center
Cleveland, Ohio, 44109
The Ohio State University
Columbus, Ohio, 43210
Henry Ford Hospital
Detroit, Michigan, 48202
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
Christiana Care Health System
Newark, Delaware, 19718
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Pulmonary Consultants and Primary Care Physicians Medical Group, Inc.
Orange, California, 92868
Pensacola Research Consultants, Inc.
Pensacola, Florida, 32504
South Jersey Infectious Disease
Somers Point, New Jersey, 08244
Los Angeles Biomedical Research Institue at Harbor UCLA Medical Center
Torrance, California, 90509
Russia8 sites
Federal State Institution
Moscow, 105203
State Moscow Healthcare
Moscow, 109240
State Healthcare Institution
Moscow, 111020
Municipal Healthcare Institution "City Clinical Hospital #2"
Novosibirsk, 630051
Regional State Healthcare
Novosibirsk, 630087
State Healthcare Institution
Saint Petersburg, 194291
State Educational Institution of Higher Professional Education
Saint Petersburg, 195067
Saint Petersburg State Healthcare Institution "City Hospital # 26"
Saint Petersburg, 196247
Argentina6 sites
Sanatorio Guemes
C.a.b.a., C1180AAX
Hospital Nuestra Señora de la Misericordia
Córdoba, X5000JRD
Hospital San Roque
Córdoba, X5000
Hospital Central de Mendoza
Mendoza, M5500CHQ
Hospital San Martín
Paraná, Entre Ríos Province, E3100BBJ
Hospital Dr. José María Cullen
Santa Fe, S3000EOZ
Georgia4 sites
Ltd Ivane Javakhishvili Tbilisi State University Center
Tbilisi, 0102
JSC K.Eristavi National Center of Experimental and Clinical Surgery
Tbilisi, 0159
Ltd Vakhtang Bochorishvili Antiseptic Center
Tbilisi, 0160
Tbilisi State Hospital #4
Tbilisi, 0160
Serbia4 sites
Clinical Hospital Centre Zvezdara
Belgrade, 11000
Emergency Centre, Clinical Centre of Serbia
Belgrade, 11000
Clincal Centre Nis
Niš, 18000
Clinical Centre of Vojvodina
Novi Sad, 21000
About this study
Official title: A Multicenter, Double-Blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA 101/ Tazobactam and Metronidazole With That of Meropenem in Complicated Intraabdominal Infections
A Phase 2, multicenter, prospective, randomized, double-blind study of CXA-101/ tazobactam (1000/500 mg q8h) and metronidazole (500 mg q8h) IV infusion vs. meropenem IV infusion (1000 mg q8h) and a matching saline placebo (q8h) in the treatment of cIAI in adult subjects. Dose adjustments for subjects with mild renal impairment are not necessary and subjects with more severe degrees of renal failure are excluded.
- Conditions
- Complicated Intra-abdominal Infection
- Being tested
- CXA-101/ tazobactam and metronidazole, meropenem plus saline placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CXA-101/ tazobactam and metronidazoleDrug
CXA-101/tazobactam (1000/500 mg q8h) plus metronidazole (500 mg q8h) administered via IV infusion
meropenem plus saline placeboDrug
meropenem IV infusion (1000 mg q8h) plus a matching saline placebo (q8h) administered via IV infusion
| Study group | Role | What they receive |
|---|---|---|
| CXA 101/tazobactam and metronidazole | Experimental | Not described Receives: Drug: CXA-101/ tazobactam and metronidazole |
| meropenem with matching saline placebo | Active comparator | Not described Receives: Drug: meropenem plus saline placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response of CXA 101/Tazobactam and Metronidazole at Test of Cure (TOC) Visit in the Microbiological Modified Intent to Treat (mMITT) Analysis Population
Clinical response is complete resolution or significant improvement of all signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
Measured: Test-of-Cure Visit (7-14 days after End of Therapy [EOT])
Secondary outcomes (1)
Microbiological Response of CXA 101/Tazobactam and Metronidazole at the TOC Visit in the Microbiologically Evaluable (ME) Population
Microbiological response is eradication (absence of the baseline pathogen from a suitable intra-abdominal specimen) or presumed eradication (absence of a suitable intra-abdominal specimen to culture at the TOC visit in a subject who is assessed as a clinical cure at TOC)
Measured: Test-of-Cure Visit (7-14 days after EOT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2010 (estimated)
- Study start25 Jun 2010
- Primary completion20 Feb 2011
- Study completion25 Mar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Complicated Intra-abdominal InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ian Friedland, MD, Study director, Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01147640
- Sponsor's protocol ID
- 7625A-012
- Other IDs
- CXA-IAI-10-01
- Status last verified
- Sep 2018
- First submitted
- 17 Jun 2010
- Last updated
- 25 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Lucasti C, Hershberger E, Miller B, Yankelev S, Steenbergen J, Friedland I, Solomkin J. Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. Antimicrob Agents Chemother. 2014 Sep;58(9):5350-7. doi: 10.1128/AAC.00049-14. Epub 2014 Jun 30.
PubMed 24982069
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-Blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA 101/ Tazobactam and Metronidazole With That of Meropenem in Complicated Intraabdominal Infections
- ClinicalTrials.gov ID
- NCT01147640
- Acronym / sponsor ID
- 7625A-012
- Conditions
- Complicated Intra-abdominal Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 25 Jun 2010 (actual)
- Primary completion
- 20 Feb 2011 (actual)
- Study completion
- 25 Mar 2011 (actual)
- First posted
- 22 Jun 2010 (estimated)
- Results
- Posted 16 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 2, multicenter, prospective, randomized, double-blind study of CXA-101/ tazobactam (1000/500 mg q8h) and metronidazole (500 mg q8h) IV infusion vs. meropenem IV infusion (1000 mg q8h) and a matching saline placebo (q8h) in the treatment of cIAI in adult subjects. Dose adjustments for subjects with mild renal impairment are not necessary and subjects with more severe degrees of renal failure are excluded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CXA 101/tazobactam and metronidazole | Experimental | Drug: CXA-101/ tazobactam and metronidazole |
| meropenem with matching saline placebo | Active comparator | Drug: meropenem plus saline placebo |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female, from 18 to 90 years of age, inclusive
- One of the following diagnoses (in which there is evidence of intraperitoneal infection) including:(a) Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall;(b)Diverticular disease with perforation or abscess; (c) Appendiceal perforation or periappendiceal abscess; (d) Acute gastric or duodenal perforation, only if operated on >24 hours after perforation occurs; (e) Traumatic perforation of the intestine, only if operated on > 12 hours after perforation occurs; (f) Peritonitis due to perforated viscus, postoperative or spread from other focus of infection (but not spontaneous [primary] bacterial peritonitis or peritonitis associated with cirrhosis and chronic ascites).Subjects with inflammatory bowel disease or ischemic bowel disease are eligible provided there is bowel perforation; or (g) Intraabdominal abscess (including liver and spleen).
- Subject 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 subject is to be enrolled preoperatively, the subject must have radiographic evidence of bowel perforation or intraabdominal abscess
- Subjects who failed prior antibacterial treatment for the current cIAI can be enrolled but must: (a) have a positive culture (from an intraabdominal site) and (b) require surgical intervention. Such subjects can be enrolled before the results of the culture are known; however, if the culture is negative, study drug administration must be discontinued.
Key exclusion criteria (24 listed)
- Women who are pregnant, nursing, or - if of child bearing potential - not using a medically accepted, effective method of birth control (e.g. condom, oral contraceptive, indwelling intrauterine device, or sexual abstinence)
- Diagnosis of abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; traumatic bowel perforation with surgery within 12 hours; perforation of gastroduodenal ulcer with surgery within 24 hours (these are considered situations of peritoneal soiling before infection has become established); another intraabdominal process in which the primary etiology is not likely to be infectious.
- Simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected, necrotizing pancreatitis, or pancreatic abscess
- cIAI managed by staged abdominal repair (STAR), open abdomen technique or any situation where infection source control is not likely to be achieved
- Known prior to randomization to have an IAI or postoperative infection caused by pathogen(s) resistant to meropenem
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CXA-101/ tazobactam and metronidazoleCXA-101/tazobactam (1000/500 mg q8h) plus metronidazole (500 mg q8h) administered via IV infusion | Drug | CXA 101/tazobactam and metronidazole |
| meropenem plus saline placebomeropenem IV infusion (1000 mg q8h) plus a matching saline placebo (q8h) administered via IV infusion | Drug | meropenem with matching saline placebo |
Primary outcome
Clinical Response of CXA 101/Tazobactam and Metronidazole at Test of Cure (TOC) Visit in the Microbiological Modified Intent to Treat (mMITT) Analysis Population
Time frame: Test-of-Cure Visit (7-14 days after End of Therapy [EOT])
Clinical response is complete resolution or significant improvement of all signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
1 secondary outcome
Microbiological Response of CXA 101/Tazobactam and Metronidazole at the TOC Visit in the Microbiologically Evaluable (ME) Population
Time frame: Test-of-Cure Visit (7-14 days after EOT)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24982069Lucasti C, Hershberger E, Miller B, Yankelev S, Steenbergen J, Friedland I, Solomkin J. Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. Antimicrob Agents Chemother. 2014 Sep;58(9):5350-7. doi: 10.1128/AAC.00049-14. Epub 2014 Jun 30.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ian Friedland, MD study director
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
33 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CXA-101/ tazobactam and metronidazole in people with Complicated Intra-abdominal Infection, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 33 sites in 5 countries.
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 24 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 25 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Russia, Argentina, Georgia, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Jan 2015). 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?
Clinical Response of CXA 101/Tazobactam and Metronidazole at Test of Cure (TOC) Visit in the Microbiological Modified Intent to Treat (mMITT) Analysis Population (time frame: Test-of-Cure Visit (7-14 days after End of Therapy [EOT])). 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 NCT01147640, which also lists 1 linked publication.
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 25 Oct 2018.