Multicenter Study to Assess the Efficacy and Safety of Eravacycline Compared with an Approved Drug, Meropenem in Complicated Intra-abdominal Infections

Phase 1

• Conditions: Complicated Intra-abdominal Infections; MedDRA version: 20.0Level: LLTClassification code 10056570Term: Intra-abdominal infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2016-002208-21-LT
• Lead Sponsor: Tetraphase Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-27
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 466

Inclusion Criteria

Male or female subject hospitalized for cIAI with one of the following diagnoses:
a. Intra-abdominal abscess: one or more abscesses surrounding diseased or perforated viscera (including hepatic and splenic abscesses)
b. Gastric or intestinal perforation associated with diffuse peritonitis
c. Peritonitis: diffuse infection of the peritoneum (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites)
d. Appendicitis with perforation, peritonitis or abscess
e. Cholecystitis with perforation or abscess
f. Diverticulitis with perforation, peritonitis, or abscess
Note: Infections limited to the hollow viscus, such as simple cholecystitis and simple appendicitis, are not eligible. Ischemic bowel disease without perforation is not eligible. Acute suppurative cholangitis and acute necrotizing pancreatitis are not eligible

2. At least 18 years of age
3. Evidence of a systemic inflammatory response with at least one of the following:
a. Fever (oral, rectal, tympanic, or by temporal artery temperature > 100.4°F / 38°C) or hypothermia (temperature = 95.9°F / 35.5°C)
b. Elevated WBC (> ULN laboratory range); or proportion of band forms of the WBC differential beyond the ULN laboratory range
c. Increased pulse (HR > 90 beats per minute)
d. Increased respiratory rate (> 20 breaths per minute)
4. Abdominal pain or flank pain (with or without rebound tenderness), or pain caused by cIAI that is referred to another anatomic area such as back or hip, or localized or diffuse abdominal wall rigidity, or mass, or ileus
5. Able to provide informed consent.
6. Subjects must agree to use a highly reliable method of birth control:
a. Male subjects must agree to use an effective barrier method of contraception during the study and for 14 days following the last dose if sexually active with a female of childbearing potential
b. Female subjects must not be pregnant or nursing. For females of childbearing potential, subjects must commit to either:
i. Use at least two medically accepted, effective methods of birth control (eg, condom, oral contraceptive, indwelling intrauterine device, hormonal implant /patch, injections, approved cervical ring, etc.) during study drug dosing and for 14 days following last study drug dose, OR
ii. Sexual abstinence

And either
7A. Meets All Inclusion Criteria for Pre-operative Enrollment:
- Has a sonogram or radiographic imaging result congruent with the diagnosis of cIAI, AND
- Acute surgical or percutaneous intervention (open laparotomy, laparoscopic surgery, or percutaneous drainage of an abscess) is foreseen within 24-h
Or
7B. Meets All Inclusion Criteria for Intra-operative/Post-operative Enrollment:
- Visual confirmation of cIAI (presence of pus within the abdominal cavity), AND
- Surgical intervention includes open laparotomy, laparoscopic surgery, or percutaneous draining of an abscess, AND
- Intervention is adequate (ie, a procedure in which all communications between the GI tract and the peritoneal cavity are closed, no necrotic intestine is left, and all infected collections are drained at the procedure), AND
- Subjects who are enrolled in the trial post-operatively must receive no more than one dose of effective antibacterial drug therapy post-operatively before randomization
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 328
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of su

Exclusion Criteria

1. Considered unlikely to survive the 6-8 week study period
• Any rapidly-progressing disease or immediately life-threatening illness, including acute hepatic failure, respiratory failure and septic shock
• Requirement for vasopressors (prior to enrollment) at therapeutic dosages (ie, dopamine > 5 µg/kg/min, any dose of norepinephrine, epinephrine or phenylephrine) to maintain a systolic blood pressure = 90 mm Hg or a mean arterial pressure = 70 mm Hg following adequate fluid resuscitation
2. Creatinine clearance = 50 mL/min as estimated by the Cockcroft-Gault equation
3. Presence or possible signs of significant hepatic disease:
a. Alanine aminotransferase or aspartate aminotransferase > 5 x ULN, OR
b. Total bilirubin > 3 x ULN, unless isolated hyperbilirubinemia is directly related to the acute process
4. Immunocompromised condition, including known HIV positivity (requiring anti-retroviral therapy or with CD4 count < 300), AIDS, organ (bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroids (eg, > 20 mg prednisone or equivalent per day for greater than 2 weeks)
5. History of moderate or severe hypersensitivity reactions to tetracyclines, carbapenems, ß-lactam antibiotics or to any of the excipients contained in the study drug formulations
6. Participation in any investigational drug or device study within 30 days prior to study entry
7. Known or suspected current central nervous system (CNS) disorder that may predispose to seizures or lower seizure threshold (eg, severe cerebral arteriosclerosis, epilepsy)
8. Antibiotic-related exclusions:
a. Receipt of effective antibacterial drug therapy for cIAI for a continuous duration of > 24-h during the 72-h preceding randomization [However, subjects with documented cIAI (ie, known baseline pathogen) who have received at least 72-h of antibiotic therapy and are considered treatment failures may be enrolled. Treatment failure is defined as persistent fever and/or clinical symptoms; or the development of a new intra-abdominal abscess after = 72-h of antibiotic therapy], OR
b. Receipt of meropenem or any other carbapenem, or tigecycline for the current infection, OR
c. Need for concomitant systemic antimicrobial agents effective in cIAI other than study drug
9. Refusal of mechanical ventilation, dialysis or hemofiltration, cardioversion or any other resuscitative measures and drug/fluid therapy at time of consent
10. Known or suspected inflammatory bowel disease or associated visceral abscess
11. The anticipated need for systemic antibiotics for a duration of more than 14 days
12. Systemic malignancy that required chemotherapy, immunotherapy, radiation therapy or antineoplastic therapy within the previous 3 months or which is anticipated to begin prior to the TOC visit
13. Known at study entry to have cIAI caused by a pathogen(s) resistant to one of the study drugs
14. Any other unstable or clinically significant concurrent medical condition (ie, class IV heart or lung disease, end stage renal disease, or requiring hemodialysis, etc.) that would, in the opinion of the investigator, jeopardize the safety of a subject, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified