Clinical trial NCT01445678: Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Complicated Intra-abdominal Infection
Keywords: cIAI
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2011-10-04
Enrollment: 494
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
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
timeFrame: TOC; 26-30 days after start of study drug administration
Secondary outcomes:
measure: The Percentage of Subjects With Microbiological Outcome of Success at the TOC Visit in the Microbiologically Evaluable (ME) Population
timeFrame: TOC; 26-30 days after start of study drug administration
measure: The Percentage of Subjects With Clinical Response at End of Therapy (EOT) Visit in the MITT Population
timeFrame: EOT; Within 24 hours of last study drug administration
measure: The Percentage of Subjects With Clinical Response at End of Therapy in the ME Population
timeFrame: EOT; Within 24 hours of last study drug administration
measure: The Percentage of Subjects With Clinical Response at Long Term Follow-Up (LFU) in the MITT Population
timeFrame: LFU; 38 to 45 days after first study drug administration
measure: The Percentage of Subjects With Clinical Response at LFU Visit in the ME Population
timeFrame: LFU; 38 to 45 days after first study drug administration
Other outcomes:
Locations:
city: Springfield
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Robbinsdale
country: United States
state: Minnesota
city: Columbus
country: United States
state: Ohio
city: Ciudadelo-Buenos Aires
country: Argentina
state: Buenos Aires
city: General Rodriguez
country: Argentina
state: Buenos Aires
city: La Plata
country: Argentina
state: Buenos Aires
city: Loma Hermosa
country: Argentina
state: Buenos Aires
city: Lujan
country: Argentina
state: Buenos Aires
city: Merlo
country: Argentina
state: Buenos Aires
city: Tandil
country: Argentina
state: Buenos Aires
city: Vicente Lopez
country: Argentina
state: Buenos Aires
city: Parana
country: Argentina
state: Entre Rios
city: Cordoba
country: Argentina
city: Corrientes
country: Argentina
city: Santa Fe
country: Argentina
city: Pleven
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Temuco
country: Chile
state: Cautin
city: Santiago
country: Chile
city: Split
country: Croatia
state: Dalmatia
city: Zagreb
country: Croatia
city: Kohtla-Jarve
country: Estonia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Freiburg
country: Germany
state: Baden-Weurttemberg
city: Heidelberg
country: Germany
state: Baden-Wuerttemberg
city: Gyula
country: Hungary
state: Bekes
city: Szeged
country: Hungary
state: Csongrad
city: Szentes
country: Hungary
state: Csongrad
city: Gyor
country: Hungary
state: Gyor-Moson-Sopron
city: Zalaegerszerg
country: Hungary
state: Zala
city: Budapest
country: Hungary
city: Kaposvar
country: Hungary
city: Kecskemet
country: Hungary
city: Vac
country: Hungary
city: Kfar Saba
country: Israel
state: Sharon
city: Tel Hashomer
country: Israel
state: Tel Aviv
city: Beer Yahkov
country: Israel
city: Haifa
country: Israel
city: Wonju
country: Korea, Republic of
state: Gangwon-Do
city: Incheon
country: Korea, Republic of
state: Gyeonggi-Do
city: Suwon-si
country: Korea, Republic of
state: Gyeonggi-Do
city: Seoul
country: Korea, Republic of
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Chisinau
country: Moldova, Republic of
city: Lodz
country: Poland
state: Lodzkie
city: Lubin
country: Poland
state: Lubelskie
city: Krakow
country: Poland
state: Malopolskie
city: Wolomin
country: Poland
state: Mazowieckie
city: Szczecin
country: Poland
state: Zachodniopomorskie
city: Belgrade
country: Serbia
city: Krafujevac
country: Serbia
city: Nis
country: Serbia
city: Novi Sad
country: Serbia
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Ellie Hershberger, Pharm.D
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Xiao 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.
citation: Kullar 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.
citation: Miller 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.
citation: Solomkin 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.