Multicenter Study to Assess the Efficacy and Safety of a study drug, Eravacycline, Compared with an approved drug, Ertapenem, in Complicated Intra-abdominal Infections

Phase 1

• Conditions: Complicated Intra-abdominal Infections; MedDRA version: 16.0Level: LLTClassification code 10056570Term: Intra-abdominal infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2013-001913-34-CZ
• Lead Sponsor: Tetraphase Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-12
• Last Update Posted: 28 November 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 536

Inclusion Criteria

1. 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
b. Gastric or intestinal perforation associated with diffuse peritonitis
c. Peritonitis due to perforated viscus, or other focus of infection (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. Intra-abdominal abscess (single or multiple), including hepatic and splenic abscesses
g. Peritonitis (local or diffuse)
Note: infections limited to the hollow viscus, such as simple cholecystitis and simple appendicitis, are not eligble. 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 (and not over 65 years of age for subjects in India)
3. Evidence of a systemic inflammatory response with at least one of the following:
a. Fever (oral, rectal or aural temperature > 100.4°F / 38°C) or hypothermia (oral temperature = 95.9°F / 35.5°C)
b. Elevated WBC (>Upper Limit of Normal (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 breathes 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. If male: must agree to use an effective barrier method of contraception during the study and for 90 days following the last dose if sexually active with a female of childbearing potential
7. If female:
a. Not pregnant or nursing
b. If of childbearing potential, will commit to either:
i. Use at least two medically accepted, effective methods of birth control (e.g., condom, oral contraceptive, indwelling intrauterine device, hormonal implant /patch, injections, approved cervical ring) during study drug dosing and for 90 days following last study drug dose
ii. Sexual abstinence

And either
8A. Meets All Inclusion Criteria for Pre-operative Enrollment:
-Clinically obvious peritonitis or has a sonogram or radiographic imaging result congruent with the diagnosis of cIAI
-Acute surgical or percutaneous intervention (open laparotomy, laparoscopic surgery, or percutaneous drainage of an abscess) is foreseen within 48-h
8B. Meets All Inclusion Criteria for Intra-operative/Post-operative Enrollment:
-Visual confirmation of cIAI (presence of pus within the abdominal cavity)
-Surgical intervention includes open laparotomy, laparoscopic surgery, or percutaneous draining of an abscess
- Initial intervention is adequate (i.e., a procedure in which all communications between the gastrointestinal (GI) tract and the peritoneal cavity are closed, no necrotic intestine is left, and all infected collections are drained at the initial procedure)
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 483
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 53

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 at therapeutic dosages (i.e., 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. Renal failure as defined as:
a. Threefold increase of serum creatinine to a known previous value or
b. Decrease in estimated glomerular filtration rate to < 75% of a known previous value or
c. Urine output of < 0.3 mL/kg per h for > 24-h or
d. Anuria for > 12-h or
e. Serum creatinine of > 4 mg/dL (353.6 µmol/L) with an acute rise of 0.5 mg/dL (42.2 µmol/L) compared with a previous value or
f. Creatinine clearance of < 30 mL/min as estimated by the Cockcroft-Gault equation = (140-age [years]
* body weight [kg] * 0.85 [if female] / 72 * serum creatinine [mg/dL] or
g. Requires peritoneal dialysis, hemodialysis or hemofiltration
3. Presence or possible signs of significant hepatic disease:
a. Alanine aminotransferase or aspartate aminotransferase > 3 x ULN; > 5 x ULN for patients with hepatic abscess or
b. Total bilirubin > 3 x ULN, unless isolated hyperbilirubinemia is directly related to the acute process or
c. Alkaline phosphatase > 3 x ULN or
d. Subjects with diagnosis of hepatic failure
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 (e.g., > 40 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 (e.g., severe cerebral arteriosclerosis, epilepsy)
8. Previously received eravacycline in a clinical trial
9. Antibiotic-related exclusions:
a. Receipt of effective antibacterial drug therapy for cIAI for a continuous duration of > 24-h during the 72-h preceding enrollment (however, subjects with documented cIAI (i.e., 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 ertapenem or any other carbapenem, or tigecycline for the current infection or
c. Need for concomitant systemic antimicrobial agents other than study drug
10. Refusal of mechanical ventilation, dialysis or hemofiltration, cardioversion or any other resuscitative measures and drug/fluid therapy at time of consent
11. Known or suspected inflammatory bowel disease or associated visceral abscess
12. The anticipated need for systemic antibiotics for a duration of more than 14 days
13. Systemic malignancy that required chemotherapy, immunotherapy, radiation therapy or antineoplastic therapy within th

Study & Design

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