Prospective, Phase 3, Randomized, Multi-center, Double-blind Study of Efiicacy, Tolerability & Safety of Sulopenem & Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro-metronidazole for Treatment of cIAI in Adults
Overview
- Phase
- Phase 3
- Intervention
- Sulopenem-Etzadroxil/Probenecid
- Conditions
- Intra Abdominal Infections
- Sponsor
- Iterum Therapeutics, International Limited
- Enrollment
- 674
- Locations
- 1
- Primary Endpoint
- Percentage of Participants With Clinical Success
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a prospective, Phase 3, randomized, multi-center, double-blind study of the efficacy, tolerability and safety of sulopenem followed by sulopenem-etzadroxil/probenecid versus ertapenem followed by ciprofloxacin-metronidazole for treatment of complicated intra-abdominal infections in adults.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient or the patient's legally acceptable representative able to provide a signed written informed consent prior to any study-specific procedures.
- •Adult patients ≥18 years of age
- •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).
- •b. Pre-operative enrollment where one of the following surgical procedures are planned within 24 hours prior to the first dose of study drug: i. Open laparotomy, percutaneous drainage of an intra-abdominal abscess, or laparoscopic surgery.
- •Evidence of systemic inflammatory indicators, with at least one of the following:
- •i. Fever (defined as body temperature \>38°C) or hypothermia with a core body temperature \<35°C ii. Elevated white blood cell count (\>12,000 cells/mm3) iii. Drop in blood pressure (systolic BP must be \<90 mmHg without pressor support) iv. Increased heart rate (\>90 bpm) and respiratory rate (\>20 breaths/min) v. Hypoxia (oxygen saturation ≤90 percent on room air)
- •Physical findings or symptoms consistent with intra-abdominal infection, with at least one of the following:
- •i. Abdominal pain and/or tenderness, with or without rebound ii. Localized or diffuse abdominal wall rigidity iii. Abdominal mass iv. Nausea/vomiting v. Altered Mental Status
- •Specimen/s from the surgical intervention were sent for culture.
Exclusion Criteria
- •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.
- •Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation.
- •Patient has simple cholecystitis or gangrenous cholecystitis without rupture, or simple appendicitis, or acute suppurative cholangitis; or infected necrotizing pancreatitis or pancreatic abscess.
- •Patient whose surgery included staged abdominal repair, or "open abdomen" technique, or marsupialization.
- •Patient known at study entry to have a complicated intra-abdominal infection caused by pathogens resistant to the study antimicrobial agents.
- •Patient needed effective concomitant systemic antibacterials (oral, IV, or intramuscular) or antifungals in addition to those designated in the 2 study groups, except vancomycin, linezolid, or daptomycin if started for known or suspected methicillin-resistant Staphylococcus aureus (MRSA) or Enterococcus spp. as per clinical study protocol (CSP).
- •Patient has perinephric infections or an indwelling peritoneal dialysis catheter.
- •Patient has suspected intra-abdominal infections due to fungus, parasites (e.g., amoebic liver abscess), virus, or tuberculosis.
- •Patient has a known history of serious allergy, hypersensitivity or any serious reaction to carbapenem antibiotics, or to other β-lactam antibiotics
- •Patient known to have any of the following laboratory values as defined below:
Arms & Interventions
Sulopenem
Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment
Intervention: Sulopenem-Etzadroxil/Probenecid
Sulopenem
Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment
Intervention: Sulopenem
Ertapenem
Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead
Intervention: Ertapenem
Ertapenem
Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead
Intervention: Ciprofloxacin
Ertapenem
Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead
Intervention: Metronidazole
Ertapenem
Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead
Intervention: Amoxicillin-Clavulanate
Outcomes
Primary Outcomes
Percentage of Participants With Clinical Success
Time Frame: Day 28 +/- 1 day
Clinical response is defined as resolution in signs and symptoms of the index infection and no new symptoms, without the need for additional antibiotics or interventions
Secondary Outcomes
- Percentage of Participants With Clinical Success(Day 11-14 +/- 1 day)