Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01147640
Other study ID # 7625A-012
Secondary ID CXA-IAI-10-01
Status Completed
Phase Phase 2
First received
Last updated
Start date June 25, 2010
Est. completion date March 25, 2011

Study information

Verified date September 2018
Source Cubist Pharmaceuticals LLC
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 122
Est. completion date March 25, 2011
Est. primary completion date February 20, 2011
Accepts healthy volunteers No
Gender All
Age group 18 Years to 90 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
CXA-101/ tazobactam and metronidazole
CXA-101/tazobactam (1000/500 mg q8h) plus metronidazole (500 mg q8h) administered via IV infusion
meropenem plus saline placebo
meropenem IV infusion (1000 mg q8h) plus a matching saline placebo (q8h) administered via IV infusion

Locations

Country Name City State
Argentina Sanatorio Guemes C.a.b.a.
Argentina Hospital Nuestra Señora de la Misericordia Cordoba
Argentina Hospital San Roque Cordoba
Argentina Hospital Central de Mendoza Mendoza
Argentina Hospital San Martín Paraná Entre Ríos
Argentina Hospital Dr. José María Cullen Santa Fe
Georgia JSC K.Eristavi National Center of Experimental and Clinical Surgery Tbilisi
Georgia Ltd Ivane Javakhishvili Tbilisi State University Center Tbilisi
Georgia Ltd Vakhtang Bochorishvili Antiseptic Center Tbilisi
Georgia Tbilisi State Hospital #4 Tbilisi
Russian Federation Federal State Institution Moscow
Russian Federation State Healthcare Institution Moscow
Russian Federation State Moscow Healthcare Moscow
Russian Federation Municipal Healthcare Institution "City Clinical Hospital #2" Novosibirsk
Russian Federation Regional State Healthcare Novosibirsk
Russian Federation Saint Petersburg State Healthcare Institution "City Hospital # 26" Saint-Petersburg
Russian Federation State Educational Institution of Higher Professional Education Saint-Petersburg
Russian Federation State Healthcare Institution Saint-Petersburg
Serbia Clinical Hospital Centre Zvezdara Belgrade
Serbia Emergency Centre, Clinical Centre of Serbia Belgrade
Serbia Clincal Centre Nis Nis
Serbia Clinical Centre of Vojvodina Novi Sad
United States University of Colorado Hospital Aurora Colorado
United States Metro Health Medical Center Cleveland Ohio
United States The Ohio State University Columbus Ohio
United States Henry Ford Hospital Detroit Michigan
United States University of Tennessee Health Science Center Memphis Tennessee
United States Christiana Care Health System Newark Delaware
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Pulmonary Consultants and Primary Care Physicians Medical Group, Inc. Orange California
United States Pensacola Research Consultants, Inc. Pensacola Florida
United States South Jersey Infectious Disease Somers Point New Jersey
United States Los Angeles Biomedical Research Institue at Harbor UCLA Medical Center Torrance California

Sponsors (1)

Lead Sponsor Collaborator
Cubist Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  Argentina,  Georgia,  Russian Federation,  Serbia, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Microbiological Response of CXA 101/Tazobactam and Metronidazole at the TOC Visit in the Microbiologically Evaluable (ME) Population Microbiological response is eradication (absence of the baseline pathogen from a suitable intra-abdominal specimen) or presumed eradication (absence of a suitable intra-abdominal specimen to culture at the TOC visit in a subject who is assessed as a clinical cure at TOC) Test-of-Cure Visit (7-14 days after EOT)
See also
  Status Clinical Trial Phase
Recruiting NCT05905055 - P3 Study to Assess Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy for Adults With Infection Due to Carbapenem Resistant Enterobacterales Phase 3
Completed NCT03293485 - Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) in Japanese Participants With Complicated Intra-abdominal Infection or Complicated Urinary Tract Infection (MK-7655A-017) Phase 3
Recruiting NCT05148702 - EXTENDed Antibiotic Durations Compared to Standard Durations for Patients With Complicated Intra-abdominal Infection. Phase 3
Completed NCT04927312 - Study to Assess Efficacy and Safety of PF-06947386 in Japanese Adult Patients With Complicated Intra-abdominal Infection Phase 3
Completed NCT00929643 - Impact Of Bacterial Resistance On Healthcare Costs For Hospitalized Patients With Complicated Intra-Abdominal Infections N/A
Completed NCT01499290 - Compare Ceftazidime-Avibactam + Metronidazole Versus Meropenem for Hospitalized Adults With Complicated Intra-Abdominal Infections Phase 3
Completed NCT01644643 - Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens Phase 3
Completed NCT01726023 - Compare Ceftazidime-Avibactam + Metronidazole vs Meropenem for Hospitalized Adults With Complicated Intra-Abd Infections Phase 3
Withdrawn NCT01602874 - Study Evaluating Tigecycline Versus Ceftriaxone In Complicated Intra-Abdominal Infections & Community Acquired Pneumonia Phase 3
Completed NCT01265784 - Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections Phase 2
Withdrawn NCT00914888 - Study Evaluating Tigecycline Versus Ceftriaxone In Complicated Intra-Abdominal Infections & Community Acquired Pneumonia Phase 3
Completed NCT00157898 - A Study to Evaluate Ertapenem Versus It's Comparator in the Treatment of Complicated Intra-abdominal Infections in Adults (0826-050)(COMPLETED) Phase 4
Recruiting NCT05733104 - A Study to Learn About the Study Medicine Zavicefta After it is Released Into the Markets in Korea
Completed NCT01445678 - Study Comparing the Safety and Efficacy of Intravenous CXA-201 and Intravenous Meropenem in Complicated Intraabdominal Infections Phase 3
Completed NCT02739997 - Study of Ceftolozane/Tazobactam (MK-7625A) in Combination With Metronidazole in Japanese Participants With Complicated Intra-abdominal Infection (MK-7625A-013) Phase 3
Completed NCT03329092 - A Study to Determine the Efficacy, Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) ± Metronidazole (MTZ) Versus Meropenem (MER) ± Colistin (COL) for the Treatment of Serious Infections Due to Gram Negative Bacteria. Phase 3
Completed NCT03217136 - MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035) Phase 2
Completed NCT01500239 - A Study Comparing Ceftazidime-Avibactam+Metronidazole Versus Meropenem in Adults With Complicated Intra-abdominal Infections Phase 3