Safety and Efficacy Study to Compare IV CXA 101/Tazobactam and Metronidazole With Meropenem in Complicated Intraabdominal Infections

NCT01147640 | Completed Phase 2 Results

• 2 other identifiers: 7625A-012CXA-IAI-10-01
• Study Type: interventional
• Target: 122
• Locations: 5 countries
• Sites: 33

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Test-of-Cure Visit (7-14 days after EOT)

Study Arms (2)

CXA 101/tazobactam and metronidazole

EXPERIMENTAL

Drug: CXA-101/ tazobactam and metronidazole

meropenem with matching saline placebo

ACTIVE COMPARATOR

Drug: meropenem plus saline placebo

Interventions

CXA-101/ tazobactam and metronidazole DRUG

CXA-101/tazobactam (1000/500 mg q8h) plus metronidazole (500 mg q8h) administered via IV infusion

CXA 101/tazobactam and metronidazole

meropenem plus saline placebo DRUG

meropenem IV infusion (1000 mg q8h) plus a matching saline placebo (q8h) administered via IV infusion

meropenem with matching saline placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

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

Study Sites (33)

Pulmonary Consultants and Primary Care Physicians Medical Group, Inc.

Orange, California, 92868, United States

Location

Los Angeles Biomedical Research Institue at Harbor UCLA Medical Center

Torrance, California, 90509, United States

Location

University of Colorado Hospital

Aurora, Colorado, 88045, United States

Location

Christiana Care Health System

Newark, Delaware, 19718, United States

Location

Pensacola Research Consultants, Inc.

Pensacola, Florida, 32504, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

Metro Health Medical Center

Cleveland, Ohio, 44109, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Tennessee Health Science Center

Memphis, Tennessee, 38163, United States

Location

Hospital San Martín

Paraná, Entre Ríos Province, E3100BBJ, Argentina

Location

Sanatorio Guemes

C.a.b.a., C1180AAX, Argentina

Location

Hospital Nuestra Señora de la Misericordia

Córdoba, X5000JRD, Argentina

Location

Hospital San Roque

Córdoba, X5000, Argentina

Location

Hospital Central de Mendoza

Mendoza, M5500CHQ, Argentina

Location

Hospital Dr. José María Cullen

Santa Fe, S3000EOZ, Argentina

Location

Ltd Ivane Javakhishvili Tbilisi State University Center

Tbilisi, 0102, Georgia

Location

JSC K.Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, 0159, Georgia

Location

Ltd Vakhtang Bochorishvili Antiseptic Center

Tbilisi, 0160, Georgia

Location

Tbilisi State Hospital #4

Tbilisi, 0160, Georgia

Location

Federal State Institution

Moscow, 105203, Russia

Location

State Moscow Healthcare

Moscow, 109240, Russia

Location

State Healthcare Institution

Moscow, 111020, Russia

Location

Municipal Healthcare Institution "City Clinical Hospital #2"

Novosibirsk, 630051, Russia

Location

Regional State Healthcare

Novosibirsk, 630087, Russia

Location

State Healthcare Institution

Saint Petersburg, 194291, Russia

Location

State Educational Institution of Higher Professional Education

Saint Petersburg, 195067, Russia

Location

Saint Petersburg State Healthcare Institution "City Hospital # 26"

Saint Petersburg, 196247, Russia

Location

Clinical Hospital Centre Zvezdara

Belgrade, 11000, Serbia

Location

Emergency Centre, Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Clincal Centre Nis

Niš, 18000, Serbia

Location

Clinical Centre of Vojvodina

Novi Sad, 21000, Serbia

Location

Related Publications (1)

• 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.

  PMID: 24982069 DERIVED

MeSH Terms

Interventions

ceftolozane; Tazobactam; Metronidazole; Meropenem

Intervention Hierarchy (Ancestors)

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

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

• Ian Friedland, MD

  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 2
• 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: June 17, 2010
• First Posted: June 22, 2010
• Study Start: June 25, 2010
• Primary Completion: February 20, 2011
• Study Completion: March 25, 2011
• Last Updated: October 25, 2018
• Results First Posted: January 16, 2015

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share

Locations

SE (4); AR (6); RU (8); US (11); GE (4)