None listed
Conditions
Interventions
Ceftriaxone sodium (or matching placebo) as a single daily dose of 2 g I.V. (infused over a 30-minute interval) plus an L-749,345 placebo (infused over a 30-minute interval) plus metronidazole at a dose of 500 mg I.V. every 8 hours (infused over a 30-minute interval)
Group name:Study group Type of group
L-749,345 (or matching placebo) as a single daily dose of 1.5 or 1g I.V. (infused over a 30-minute interval) plus a ceftriaxone sodium placebo (infused over a 30-minute interval) plus metronidazole placebo I.V. every 8 hours (infused over a 30-minute interval)
Sponsors
MERCK SHARP & DOHME PERU S.R.L.,
Eligibility
Inclusion criteria
Inclusion criteria: - Patient has a clinically suspected and/or bacteriologically documented infections diagnosis appropriate for study, according to the following diagnostic criteria: 1) intra-Abdominal Infection based on history, physical findings, and laboratory evaluation (either oral temperature >38°C or rectal temperature >38.6°C; WBC>10.5x10^3/mm3; abdominal tenderness and pain supportive of a diagnosis of intra-abdominal infection, and/or CT scan, MRI or radionuclide changes consistent with intra-abdominal infection) 2) Infection extends or is presumed to extend beyond the wall of a hollow organ (e.g., peritonitis, gangrene, abscess, cholecystitis with inflammation outside the gallbladder). Patients diagnosed with appendicitis are eligible for inclusion only if symptoms developed outside the hospital and there is a history of symptoms for >24 hours but 101.5°F or 38.6°C, and WBC>13,500/mm^, and either: a) physical exam evidence of peritoneal irritation extending beyond the local site of infection; or b) radiologic evidence of an abscess. 3) Infection is caused or presumed to be caused by microorganisms susceptible to the intravenous study antibiotics (L-749,345 or ceftriaxone sodium and metronidazole). Patients diagnosed with infections of a hollow organ will only be considered fully evaluable if etiologic microorganisms susceptible to the intravenous study antibiotics (L-749,345 or ceftriaxone sodium and metronidazole) are isolated from an intraperitoneal source, or from the external surface of the hollow viscus (prior to incision of a hollow viscus). - Patient is an adult (male or female) between the ages of 18 and 75 years. - Absolute neutrophil count >3,000 cells/mm3. - Females of childbearing potential must have a negative serum pregnancy test (b-HCG) prior to enrollment into the study and subsequently until 1-month after discontinuation of study treatment use adequate birth control measures as defined by the investigator. Oral contraceptives should not be used as the sole method of birth control, because the effect of L-749,345 on the efficacy of oral contraceptives has not yet been established. - Patient´s infection is characterized by the investigator as serious (requiring hospitalization), complicated (requiring surgical intervention with 24 hours after diagnosis), and mild to moderate in severity (not life-threatening). Surgical intervention can be open surgery, percutaneous drainage of an abscess, or laparoscopic surgery where cultures are positive from the peritoneal surface. - Patient´s infection is caused or thought to be caused by microorganisms susceptible in vitro to the intravenous study antibiotic(s), in the opinion of the investigator. Patients will only be considered microbiologically evaluable if an etiologic pathogen(s) susceptible to the study antibiotic is (are) isolated from a clinically relevant specimen in the initial/pre-study culture. Patients with a polymicrobial infection where one or more pathogens are resistant in vitro to the study antibiotic may be included at the discretion of the investigator if a pathogen that is susceptible in vitro to the intravenous study antibiotic(s) has also been isolated. - Patient´s infection has not been treated with more than 24 hours of systemic antibiotic therapy known to be effective against the presumed etiologic pathogen(s) within the 72-hour period immediately prior to consideration for entry into the study.
Exclusion criteria
Exclusion criteria: - Failure to meet all inclusion criteria. - Infection diagnosis of simple cholecystitis, traumatic bowel perforation requiring surgery within 12 hours, perforation of gastroduodenal ulcers requiring surgery within 24 hours, or other intra-abdominal processes in which the primary etiology is not likely to be infectious. - Ischemic bowel disease. - History of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to carbapenem antibiotics (such as imipenem), ceftriaxone sodium, any cephalosporins or penicillins, or metronidazole and metronidazole derivatives. Patients with a history of mild rash to penicillin may be enrolled. - History of allergy, hypersensitivity, intolerance, or any other adverse reaction to an injectable multivitamin or any of its components. - Rapidly progressive or terminal illness; patients in whom a response to antibiotic therapy is considered unlikely or patients who are considered unlikely to survive the study period. - Pregnant women, nursing women, or fertile women not practicing adequate methods of contraception; women planning to become pregnant within 1 month of the study. - Treatment with a systemic antibiotic within the 72-hour period immediately prior to consideration for entry into the study, unless either: 1) Treatment during the 72-hour period consisted of 3x the upper limit of the range of normal values used by the laboratory performing the test. Exceptions will be considered for patients with infections of the biliary system in whom these abnormalities are considered due to the acute infectious process. - Hematocrit 1.5x upper limit of normal. - History of any illness that, in the opinion of the inv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The proportion of patients who have both a favorable clinical and microbiological response assessment (overall and by pathogen) at the late follow-up visit. Measure:Primary clinical and microbiological effectiveness criteria Timepoints:4 to 6 weeks after discontinuation of all antibiotic therapy ; Outcome name:The primary safety variable will be the proportion of patients within each treatment group that experiences one or more drug-related adverse events. Measure:Primary safety criteria Timepoints:Throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The proportion of patients who have both a favorable clinical and microbiological response assessment (overall and by pathogen) at the early follow-up visit. Measure:Secondary clinical and microbiological effectiveness criteria Timepoints:7 to 10 days after discontinuation of all antibiotic therapy | — |
Contacts
Public ContactStela Lopez
MERCK SHARP & DOHME PERU S.R.L
Outcome results
None listed