Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections

NCT01445678 | Completed Phase 3 Results

• 3 other identifiers: 7625A-004CXA-cIAI-10-09CXA-cIAI-10-08
• Study Type: interventional
• Target: 494
• Locations: 15 countries
• Sites: 61

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).

Conditions

Complicated Intra-abdominal Infection

Keywords

cIAI

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  EOT; Within 24 hours of last study drug administration

• The Percentage of Subjects With Clinical Response at End of Therapy in the ME Population

  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

  LFU; 38 to 45 days after first study drug administration

• The Percentage of Subjects With Clinical Response at LFU Visit in the ME Population

  LFU; 38 to 45 days after first study drug administration

Study Arms (2)

CXA-201 and Metronidazole as treatment for cIAI

EXPERIMENTAL

Drug: CXA-201 and metronidazole

Meropenem as treatment for cIAI

ACTIVE COMPARATOR

Drug: Meropenem

Interventions

CXA-201 and metronidazole DRUG

CXA-201 IV infusion (1500mg q8h) and metronidazole IV infusion (500mg q 8h) for 4-14 days

CXA-201 and Metronidazole as treatment for cIAI

Meropenem DRUG

Meropenem IV infusion (1000mg q8h) for 4-14 days

Meropenem as treatment for cIAI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (61)

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Springfield, Illinois, United States

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Boston, Massachusetts, United States

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Robbinsdale, Minnesota, United States

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Columbus, Ohio, United States

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Ciudadelo-Buenos Aires, Buenos Aires, Argentina

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General Rodríguez, Buenos Aires, Argentina

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La Plata, Buenos Aires, Argentina

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Loma Hermosa, Buenos Aires, Argentina

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Luján, Buenos Aires, Argentina

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Merlo, Buenos Aires, Argentina

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Tandil, Buenos Aires, Argentina

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Vicente López, Buenos Aires, Argentina

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Paraná, Entre Ríos Province, Argentina

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Corrientes, Argentina

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Córdoba, Argentina

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Santa Fe, Argentina

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Pleven, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Temuco, Cautin, Chile

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Santiago, Chile

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Split, Dalmatia, Croatia

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Zagreb, Croatia

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Kohtla-Järve, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Freiburg im Breisgau, Baden-Weurttemberg, Germany

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Heidelberg, Baden-Wurttemberg, Germany

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Gyula, Bekes County, Hungary

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Szeged, Csongrád megye, Hungary

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Szentes, Csongrád megye, Hungary

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Győr, Győr-Moson-Sopron, Hungary

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Zalaegerszerg, Zala County, Hungary

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Budapest, Hungary

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Kaposvár, Hungary

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Kecskemét, Hungary

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Vác, Hungary

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Kfar Saba, Sharon, Israel

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Tel Litwinsky, Tel Aviv, Israel

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Beer Yahkov, Israel

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Haifa, Israel

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Liepāja, Latvia

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Riga, Latvia

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Šiauliai, Lithuania

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Vilnius, Lithuania

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Chisinau, Moldova

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Krakow, Lesser Poland Voivodeship, Poland

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Lubin, Lublin Voivodeship, Poland

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Wołomin, Masovian Voivodeship, Poland

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Szczecin, West Pomeranian Voivodeship, Poland

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Lodz, Łódź Voivodeship, Poland

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Belgrade, Serbia

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Krafujevac, Serbia

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Niš, Serbia

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Novi Sad, Serbia

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Wŏnju, Gangwon-do, South Korea

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Incheon, Gyeonggi-do, South Korea

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Suwon, Gyeonggi-do, South Korea

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Seoul, South Korea

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Related Publications (5)

• 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.

  PMID: 28464828 DERIVED

• 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.

  PMID: 28446129 DERIVED

• 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.

  PMID: 27999024 DERIVED

• 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.

  PMID: 27139477 DERIVED

• 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.

  PMID: 25670823 DERIVED

MeSH Terms

Interventions

Metronidazole; Meropenem

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Two identical P3 protocols were initiated (NCT01445678 and NCT01445665) subsequently, Cubist and FDA agreed that integrated data from the 2 protocols could be analyzed and reported in a single Clinical Study Report. These analyses are presented here.

Results Point of Contact

• Title: Dr. Obi Umeh, Vice President Global Medical Sciences
• Organization: Cubist Pharmaceuticals, Inc.

obiamiwe.umeh@cubist.com

781-860-8415

Study Officials

• Ellie Hershberger, Pharm.D

  Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2011
• First Posted: October 4, 2011
• Study Start: December 23, 2011
• Primary Completion: October 3, 2013
• Study Completion: October 15, 2013
• Last Updated: November 16, 2018
• Results First Posted: January 15, 2015

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share

Locations

CL (2); DE (2); PL (5); CR (2); LI (4); LA (2); MO (1); ES (3); US (4); AR (12); SE (4); KR (4); BU (3); HU (9); IL (4)