Complicated Intra-abdominal InfectionPhase 3NCT01445678
Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections
A Phase 3 study testing CXA-201 and metronidazole and Meropenem in people with Complicated Intra-abdominal Infection, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 61 sites in 15 countries.
Trial summary
This is a Phase 3, multicenter, prospective, randomized, double-blind, double dummy study of CXA-201 Intravenous (IV) infusions (1500mg q8h) and metronidazole (500mg q8h) versus meropenem (1000mg q8h)for the treatment of adults with Complicated Intraabdominal Infections (cIAI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complicated Intra-abdominal Infection
- What is being tested?
- CXA-201 and metronidazole and Meropenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 494 participants
- Where
- 61 sitesin 15 countries
- Study dates
- 23 Dec 2011to 15 Oct 2013
- 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
- Diagnoses of cIAI.
- 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.
Who cannot join
- Simple appendicitis; acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess; or pelvic infections.
- Complicated intraabdominal infection managed by staged abdominal repair (STAR), open abdomen technique including temporary closure of the abdomen, or any situation where infection source control is not likely to be achieved.
- Use of systemic antibiotic therapy for IAI for more than 24 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy.
- Have a concomitant infection at the time of randomization, which requires non-study systemic antibacterial therapy in addition to IV study drug therapy. (Drugs with only gram-positive activity [e.g., daptomycin, vancomycin, linezolid] are allowed).
- Severe impairment of renal function (estimated CrCl < 30 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 at baseline.
Show all 10Show fewer
- Considered unlikely to survive the 4 to 5 week study period.
- Any rapidly-progressing disease or immediately life-threatening illness (including respiratory failure and septic shock).
- Have a documented history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibacterial (a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment), including cephalosporins, carbapenems, penicillins, or ß-lactamase inhibitors, or metronidazole, or nitroimidazole derivatives.
- Women who are pregnant or nursing.
Trial locations and contacts
61 sites in 15 countries.
61 sites in 15 countries
Argentina12 sites
Study site
Ciudadelo-Buenos Aires, Buenos Aires
Study site
Córdoba
Study site
Corrientes
Study site
General Rodriguez, Buenos Aires
Study site
La Plata, Buenos Aires
Study site
Loma Hermosa, Buenos Aires
Study site
Luján, Buenos Aires
Study site
Merlo, Buenos Aires
Study site
Paraná, Entre Ríos Province
Study site
Santa Fe
Study site
Tandil, Buenos Aires
Study site
Vicente López, Buenos Aires
Hungary9 sites
Study site
Budapest
Study site
Győr, Győr-Moson-Sopron
Study site
Gyula, Bekes County
Study site
Kaposvár
Study site
Kecskemét
Study site
Szeged, Csongrád megye
Study site
Szentes, Csongrád megye
Study site
Vác
Study site
Zalaegerszerg, Zala County
Poland5 sites
Study site
Krakow, Lesser Poland Voivodeship
Study site
Lodz, Łódź Voivodeship
Study site
Lubin, Lublin Voivodeship
Study site
Szczecin, West Pomeranian Voivodeship
Study site
Wołomin, Masovian Voivodeship
United States4 sites
Study site
Boston, Massachusetts
Study site
Columbus, Ohio
Study site
Robbinsdale, Minnesota
Study site
Springfield, Illinois
Israel4 sites
Study site
Beer Yahkov
Study site
Haifa
Study site
Kfar Saba, Sharon
Study site
Tel HaShomer, Tel Aviv
Lithuania4 sites
Study site
Kaunas
Study site
Klaipėda
Study site
Šiauliai
Study site
Vilnius
Serbia4 sites
Study site
Belgrade
Study site
Krafujevac
Study site
Niš
Study site
Novi Sad
South Korea4 sites
Study site
Incheon, Gyeonggi-do
Study site
Seoul
Study site
Suwon, Gyeonggi-do
Study site
Wŏnju, Gangwon-do
Germany2 sites
Study site
Freiburg im Breisgau, Baden-Weurttemberg
Study site
Heidelberg, Baden-Wurttemberg
About this study
Official title: A Multicenter, Double-Blind, Randomized, Phase 3 Study to Compare the Efficacy and Safety of Intravenous CXA-201 With That of Meropenem in Complicated Intraabdominal Infections
This is a Phase 3, multicenter, prospective, randomized, double-blind, double dummy study of CXA-201 Intravenous (IV) infusions (1500mg q8h) and metronidazole (500mg q8h) versus meropenem (1000mg q8h)for the treatment of adults with Complicated Intraabdominal Infections (cIAI).
Read the detailed description
Approximately, 500 subjects will be enrolled into this study, randomized 1:1 to receive CXA-201 and metronidazole or comparator (meropenem). Subject participation will require a minimum commitment of 38 days and a maximum of 45 days. An End of Treatment (EOT) visit will occur within 24 hours following the last dose of study drug administration/drug discontinuation. A Test of Cure (TOC)/Safety visit will be conducted 26 to 30 days following the first dose of study drug administration. A Last Follow-up (LFU) visit will be conducted 38 to 45 days after the first dose of study drug.
- Conditions
- Complicated Intra-abdominal Infection
- Being tested
- CXA-201 and metronidazole, Meropenem
- Keywords
- cIAI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CXA-201 and metronidazoleDrug
CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days
MeropenemDrug
Meropenem IV infusion (1000mg q8h) for 4-14 days
| Study group | Role | What they receive |
|---|---|---|
| CXA-201 and Metronidazole as treatment for cIAI | Experimental | Not described Receives: Drug: CXA-201 and metronidazole |
| Meropenem as treatment for cIAI | Active comparator | Not described Receives: Drug: Meropenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Subjects With Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population
Clinical cure is complete resolution or significant improvement in 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: TOC; 26-30 days after start of study drug administration
Secondary outcomes (5)
The Percentage of Subjects With Microbiological Outcome of Success at the TOC Visit in the Microbiologically Evaluable (ME) Population
Success is eradication (absence of the baseline pathogen in a specimen appropriately obtained from the original site of infection) or presumed eradication (absence of material to culture in a subject who was assessed as a clinical cure) for each baseline pathogen
Measured: TOC; 26-30 days after start of study drug administration
The Percentage of Subjects With Clinical Response at End of Therapy (EOT) Visit in the MITT Population
Clinical response is complete resolution or significant improvement in 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: EOT; Within 24 hours of last study drug administration
The Percentage of Subjects With Clinical Response at End of Therapy in the ME Population
Clinical response is complete resolution or significant improvement in 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: EOT; Within 24 hours of last study drug administration
The Percentage of Subjects With Clinical Response at Long Term Follow-Up (LFU) in the MITT Population
Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit.
Measured: LFU; 38 to 45 days after first study drug administration
The Percentage of Subjects With Clinical Response at LFU Visit in the ME Population
Clinical response is clinical cure at TOC and no signs and symptoms recur or worsen since the TOC visit
Measured: LFU; 38 to 45 days after first study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2011 (estimated)
- Study start23 Dec 2011
- Primary completion3 Oct 2013
- Study completion15 Oct 2013
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 (5)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 494 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
- Ellie Hershberger, Pharm.D, Study director, Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01445678
- Sponsor's protocol ID
- 7625A-004
- Other IDs
- CXA-cIAI-10-09, CXA-cIAI-10-08
- Status last verified
- Oct 2018
- First submitted
- 26 Sep 2011
- Last updated
- 16 Nov 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
Popejoy MW, Long J, Huntington JA. Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam. BMC Infect Dis. 2017 May 2;17(1):316. doi: 10.1186/s12879-017-2414-9.
PubMed 28464828Xiao Y, Tong ML, Liu LL, Lin LR, Chen MJ, Zhang HL, Zheng WH, Li SL, Lin HL, Lin ZF, Xing HQ, Niu JJ, Yang TC. Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study. BMC Infect Dis. 2017 Apr 26;17(1):310. doi: 10.1186/s12879-017-2339-3.
PubMed 28446129Kullar R, Wagenlehner FM, Popejoy MW, Long J, Yu B, Goldstein EJ. Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. J Antimicrob Chemother. 2017 Mar 1;72(3):900-905. doi: 10.1093/jac/dkw486.
PubMed 27999024Miller B, Popejoy MW, Hershberger E, Steenbergen JN, Alverdy J. Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study. Antimicrob Agents Chemother. 2016 Jun 20;60(7):4387-90. doi: 10.1128/AAC.03074-15. Print 2016 Jul.
PubMed 27139477Solomkin J, Hershberger E, Miller B, Popejoy M, Friedland I, Steenbergen J, Yoon M, Collins S, Yuan G, Barie PS, Eckmann C. Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI). Clin Infect Dis. 2015 May 15;60(10):1462-71. doi: 10.1093/cid/civ097. Epub 2015 Feb 10.
PubMed 25670823
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Double-Blind, Randomized, Phase 3 Study to Compare the Efficacy and Safety of Intravenous CXA-201 With That of Meropenem in Complicated Intraabdominal Infections
- ClinicalTrials.gov ID
- NCT01445678
- Acronym / sponsor ID
- 7625A-004
- Conditions
- Complicated Intra-abdominal Infection
- Keywords
- cIAI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 494 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 23 Dec 2011 (actual)
- Primary completion
- 3 Oct 2013 (actual)
- Study completion
- 15 Oct 2013 (actual)
- First posted
- 4 Oct 2011 (estimated)
- Results
- Posted 15 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, multicenter, prospective, randomized, double-blind, double dummy study of CXA-201 Intravenous (IV) infusions (1500mg q8h) and metronidazole (500mg q8h) versus meropenem (1000mg q8h)for the treatment of adults with Complicated Intraabdominal Infections (cIAI).
Detailed description
Approximately, 500 subjects will be enrolled into this study, randomized 1:1 to receive CXA-201 and metronidazole or comparator (meropenem). Subject participation will require a minimum commitment of 38 days and a maximum of 45 days. An End of Treatment (EOT) visit will occur within 24 hours following the last dose of study drug administration/drug discontinuation. A Test of Cure (TOC)/Safety visit will be conducted 26 to 30 days following the first dose of study drug administration. A Last Follow-up (LFU) visit will be conducted 38 to 45 days after the first dose of study drug.
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-201 and Metronidazole as treatment for cIAI | Experimental | Drug: CXA-201 and metronidazole |
| Meropenem as treatment for cIAI | Active comparator | Drug: Meropenem |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnoses of cIAI.
- 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.
Key exclusion criteria (10 listed)
- Simple appendicitis; acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess; or pelvic infections.
- Complicated intraabdominal infection managed by staged abdominal repair (STAR), open abdomen technique including temporary closure of the abdomen, or any situation where infection source control is not likely to be achieved.
- Use of systemic antibiotic therapy for IAI for more than 24 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy.
- Have a concomitant infection at the time of randomization, which requires non-study systemic antibacterial therapy in addition to IV study drug therapy. (Drugs with only gram-positive activity [e.g., daptomycin, vancomycin, linezolid] are allowed).
- Severe impairment of renal function (estimated CrCl < 30 mL/min), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours).
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-201 and metronidazoleCXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days | Drug | CXA-201 and Metronidazole as treatment for cIAI |
| MeropenemMeropenem IV infusion (1000mg q8h) for 4-14 days | Drug | Meropenem as treatment for cIAI |
Primary outcome
The Percentage of Subjects With Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population
Time frame: TOC; 26-30 days after start of study drug administration
Clinical cure is complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure was required for the index infection.
5 secondary outcomes
The Percentage of Subjects With Microbiological Outcome of Success at the TOC Visit in the Microbiologically Evaluable (ME) Population
Time frame: TOC; 26-30 days after start of study drug administration
The Percentage of Subjects With Clinical Response at End of Therapy (EOT) Visit in the MITT Population
Time frame: EOT; Within 24 hours of last study drug administration
The Percentage of Subjects With Clinical Response at End of Therapy in the ME Population
Time frame: EOT; Within 24 hours of last study drug administration
The Percentage of Subjects With Clinical Response at Long Term Follow-Up (LFU) in the MITT Population
Time frame: LFU; 38 to 45 days after first study drug administration
The Percentage of Subjects With Clinical Response at LFU Visit in the ME Population
Time frame: LFU; 38 to 45 days after first study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28464828Popejoy MW, Long J, Huntington JA. Analysis of patients with diabetes and complicated intra-abdominal infection or complicated urinary tract infection in phase 3 trials of ceftolozane/tazobactam. BMC Infect Dis. 2017 May 2;17(1):316. doi: 10.1186/s12879-017-2414-9.
- Derived from this study: PubMed 28446129Xiao Y, Tong ML, Liu LL, Lin LR, Chen MJ, Zhang HL, Zheng WH, Li SL, Lin HL, Lin ZF, Xing HQ, Niu JJ, Yang TC. Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study. BMC Infect Dis. 2017 Apr 26;17(1):310. doi: 10.1186/s12879-017-2339-3.
- Derived from this study: PubMed 27999024Kullar R, Wagenlehner FM, Popejoy MW, Long J, Yu B, Goldstein EJ. Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. J Antimicrob Chemother. 2017 Mar 1;72(3):900-905. doi: 10.1093/jac/dkw486.
- Derived from this study: PubMed 27139477Miller B, Popejoy MW, Hershberger E, Steenbergen JN, Alverdy J. Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study. Antimicrob Agents Chemother. 2016 Jun 20;60(7):4387-90. doi: 10.1128/AAC.03074-15. Print 2016 Jul.
- Derived from this study: PubMed 25670823Solomkin J, Hershberger E, Miller B, Popejoy M, Friedland I, Steenbergen J, Yoon M, Collins S, Yuan G, Barie PS, Eckmann C. Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI). Clin Infect Dis. 2015 May 15;60(10):1462-71. doi: 10.1093/cid/civ097. Epub 2015 Feb 10.
- 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.
Ellie Hershberger, Pharm.D study director
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
61 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CXA-201 and metronidazole and Meropenem in people with Complicated Intra-abdominal Infection, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 61 sites in 15 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 2 inclusion and 10 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 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in Argentina, Hungary, Poland, United States, Israel and 10 more countries. 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 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 15 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?
The Percentage of Subjects With Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population (time frame: TOC; 26-30 days after start of study drug administration). 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 NCT01445678, which also lists 5 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 16 Nov 2018.