To compare the efficacy of sulopenem followed by sulopenem etzadroxil with probenecid versus ertapenem followed by ciprofloxacin and metronidazole or amoxicillin-clavulanate for treatment of complicated intra-abdominal infection in adults, on Day 28 (test of cure [TOC]) post randomization.
- Conditions
- Complicated intra-abdominal infectionTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2017-003773-34-LV
- Lead Sponsor
- Iterum Therapeutics International Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 670
1. Patient able to provide a signed written informed consent prior to any study-specific procedures.
2. Adult patients =18 years of age
3. EITHER:
a. Intra-operative/post-operative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least 1 of the following diagnosed during the surgical intervention:
i. Cholecystitis with gangrenous rupture or perforation or progression of the infection beyond the gallbladder wall
ii. Diverticular disease with perforation or abscess
iii. Appendiceal perforation or peri-appendiceal abscess
iv. Traumatic perforation of the intestines, only if operated on >12 hours after perforation occurs
v. Secondary peritonitis (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites)
vi. Intra-abdominal abscess (including of liver or spleen provided that there was extension beyond the organ with evidence of intraperitoneal involvement).
OR:
b. Pre-operative enrollment where one of the following surgical procedures are planned within 24 hours of the first dose of study drug:
i. Open laparotomy, percutaneous drainage of an intra-abdominal abscess, or laparoscopic surgery.
4. Evidence of systemic inflammatory indicators, with at least one of the following:
a. Fever (defined as body temperature >38°C) or hypothermia with a core body temperature <35°C
b. Elevated white blood cell count (>12,000 cells/mm3) or leukopenia (defined as white blood cell count <4,000 cells/mm3)
c. Drop in blood pressure (systolic BP must be <90 mmHg without pressor support)
d. Increased heart rate (>90 bpm) and respiratory rate (>20 breaths/min)
e. Hypoxia (oxygen saturation =90 percent on room air)
5. Physical findings or symptoms consistent with intra-abdominal infection, with at least one of the following:
a. Abdominal pain and/or tenderness, with or without rebound
b. Localized or diffuse abdominal wall rigidity
c. Abdominal mass
d. Nausea and/or vomiting
e. Altered Mental Status
6. Specimen/s from the surgical intervention were sent or planned to be sent for culture.
Microbiologic specimens collected during routine operative care prior to subject providing informed consent may be used for study purposes.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 469
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 201
1. Patient diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which the primary etiology was not likely to be infectious.
2. Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation.
3. Patient has simple cholecystitis or gangrenous cholecystitis without rupture, or simple appendicitis, or acute suppurative cholangitis; or infected necrotizing pancreatitis or pancreatic abscess.
4. Patient whose surgery included staged abdominal repair, or open abdomen” technique, or marsupialization.
5. Patient known at study entry to have a complicated intra-abdominal infection caused by pathogens non-susceptible to the study antimicrobial agents.
6. Patient needed effective concomitant systemic antibacterials or antifungals in addition to those designated in the 2 study groups, except vancomycin, linezolid, or daptomycin if started for known or suspected MRSA or Enterococcus spp.
7. Patient has perinephric infections or an indwelling peritoneal dialysis catheter.
8. Patient has suspected intra-abdominal infections due to fungus, parasites, virus, or tuberculosis.
9. Patient with known history of serious allergy, hypersensitivity or any serious reaction to carbapenem antibiotics, other ß-lactam antibiotics, quinolones, metronidazole, or probenecid, as formulated with their excipients.
10. Patient known to have any of the following laboratory values as defined below:
a. Hematocrit <25% or hemoglobin <8 g/dL
b. Absolute neutrophil count <1000/mm3
c. Platelet count <75,000/mm3
d. Bilirubin >3 x the ULN, unless isolated hyperbilirubinemia was directly related to the acute infection or known Gilbert’s disease
e. ALT or AST >3 x ULN values at Screening. Patients with elevations of AST and/or ALT up to 5 x ULN will be eligible if these elevations are acute and directly related to the infectious process being treated. This must be documented
f. ALP >3 x ULN. Patients with values >3.0 x ULN and <5.0 x ULN are eligible if this value is acute and directly related to the infectious process being treated. This must be documented.
11. Patient has a body mass index >45 kg/m2.
12. Patient has APACHE II score >30 (serum bicarbonate may be used in place of arterial blood gases).
13. Patient considered unlikely to survive the 4-week study period or has a rapidly progressive or terminal illness, including septic shock that was associated with a high risk of mortality.
14. Patient unlikely to respond to 10–14 days of treatment with antibiotics.
15. Patient received systemic antibacterial agents within the 72-hour period prior to study entry, unless either of the following pertained:
a. Patient has new infection (not considered a treatment failure) and both of the following were met:
i. Patient received no more than 24 hours of total prior antibiotic therapy
ii. Patient received =1 dose of a treatment regimen post-operatively and antibiotics were not received more than 6 hours post-procedure.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method