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

NCT ID: NCT01147640

Last Updated: 2018-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-25
• Study Completion Date: 2011-03-25

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CXA 101/tazobactam and metronidazole

Group Type: EXPERIMENTAL

CXA-101/ tazobactam and metronidazole

Intervention Type: DRUG

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

meropenem with matching saline placebo

Group Type: ACTIVE_COMPARATOR

meropenem plus saline placebo

Intervention Type: DRUG

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

Interventions

CXA-101/ tazobactam and metronidazole

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

Intervention Type: DRUG

meropenem plus saline placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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).
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ian Friedland, MD

Role: STUDY_DIRECTOR

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

Locations

Pulmonary Consultants and Primary Care Physicians Medical Group, Inc.

Orange, California, United States

Los Angeles Biomedical Research Institue at Harbor UCLA Medical Center

Torrance, California, United States

University of Colorado Hospital

Aurora, Colorado, United States

Christiana Care Health System

Newark, Delaware, United States

Pensacola Research Consultants, Inc.

Pensacola, Florida, United States

Henry Ford Hospital

Detroit, Michigan, United States

South Jersey Infectious Disease

Somers Point, New Jersey, United States

Metro Health Medical Center

Cleveland, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

University of Tennessee Health Science Center

Memphis, Tennessee, United States

Hospital San Martín

Paraná, Entre Ríos Province, Argentina

Sanatorio Guemes

C.a.b.a., , Argentina

Hospital Nuestra Señora de la Misericordia

Córdoba, , Argentina

Hospital San Roque

Córdoba, , Argentina

Hospital Central de Mendoza

Mendoza, , Argentina

Hospital Dr. José María Cullen

Santa Fe, , Argentina

Ltd Ivane Javakhishvili Tbilisi State University Center

Tbilisi, , Georgia

JSC K.Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, , Georgia

Ltd Vakhtang Bochorishvili Antiseptic Center

Tbilisi, , Georgia

Tbilisi State Hospital #4

Tbilisi, , Georgia

Federal State Institution

Moscow, , Russia

State Moscow Healthcare

Moscow, , Russia

State Healthcare Institution

Moscow, , Russia

Municipal Healthcare Institution "City Clinical Hospital #2"

Novosibirsk, , Russia

Regional State Healthcare

Novosibirsk, , Russia

State Healthcare Institution

Saint Petersburg, , Russia

State Educational Institution of Higher Professional Education

Saint Petersburg, , Russia

Saint Petersburg State Healthcare Institution "City Hospital # 26"

Saint Petersburg, , Russia

Clinical Hospital Centre Zvezdara

Belgrade, , Serbia

Emergency Centre, Clinical Centre of Serbia

Belgrade, , Serbia

Clincal Centre Nis

Niš, , Serbia

Clinical Centre of Vojvodina

Novi Sad, , Serbia

Countries

United States; Argentina; Georgia; Russia; Serbia

References

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.

Reference Type: DERIVED

PMID: 24982069 (View on PubMed)

Other Identifiers

CXA-IAI-10-01

Identifier Type: OTHER

Identifier Source: secondary_id

7625A-012

Identifier Type: -

Identifier Source: org_study_id