Efficacy and Safety Study of Eravacycline Compared With Meropenem in Complicated Intra-abdominal Infections
Condition: Complicated Intra-abdominal Infections; Complicated Appendicitis
MeSH terms: Infections; Communicable Diseases; Appendicitis; Intraabdominal Infections
Intervention: Eravacycline; Meropenem; Placebo
Intervention MeSH terms: Meropenem
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 500.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to
      assess the efficacy, safety, and pharmacokinetics (PK) of eravacycline compared with
      meropenem in the treatment of complicated intra-abdominal infections (cIAIs).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female participant hospitalized for cIAI

          -  At least 18 years of age

          -  Evidence of a systemic inflammatory response

          -  Abdominal pain or flank pain (with or without rebound tenderness), or pain caused by
             cIAI that is referred to another anatomic area

          -  Able to provide informed consent

          -  If male: 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

          -  If female, not pregnant or nursing or, if of childbearing potential: either will
             commit to use at least two medically accepted, effective methods of birth control (for
             example, condom, oral contraceptive, indwelling intrauterine device, hormonal implant
             /patch, injections, approved cervical ring) during study drug dosing and for 14 days
             following last study drug dose or practicing sexual abstinence

        Exclusion Criteria:

          -  Unlikely to survive the 6-8 week study period

          -  Creatinine clearance of ≤50 milliliter (mL)/minute

          -  Presence or possible signs of significant hepatic disease

          -  Immunocompromised condition, including known human immunodeficiency virus (HIV)
             positivity, transplant recipients, and hematological malignancy

          -  History of moderate or severe hypersensitivity reactions to tetracyclines,
             carbapenems, β-lactam antibiotics, or to any of the excipients contained in the study
             drug formulations

          -  Participation in any investigational drug or device study within 30 days prior to
             study entry

          -  Known or suspected current central nervous system (CNS) disorder that may predispose
             to seizures or lower seizure threshold (for example, severe cerebral arteriosclerosis,
             epilepsy)

          -  Antibiotic-related exclusions:

               1. Receipt of effective antibacterial drug therapy for cIAI for a continuous
                  duration of >24-hours during the 72-hours preceding randomization [however,
                  participants with documented cIAI (that is, known baseline pathogen) who have
                  received at least 72-hours 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-hours of antibiotic therapy], or

               2. Receipt of meropenem or any other carbapenem, or tigecycline for the current
                  infection, or

               3. Need for concomitant systemic antimicrobial agents effective in cIAI other than
                  study drug

          -  Refusal of mechanical ventilation, dialysis or hemofiltration, cardioversion, or any
             other resuscitative measures and drug/fluid therapy at time of consent

          -  Known or suspected inflammatory bowel disease or associated visceral abscess

          -  The anticipated need for systemic antibiotics for a duration of more than 14 days

          -  Systemic malignancy that required chemotherapy, immunotherapy, radiation therapy, or
             antineoplastic therapy within the previous 3 months or that is anticipated to begin
             prior to the Test-of-Cure (TOC) visit

          -  Known at study entry to have cIAI caused by a pathogen(s) resistant to one of the
             study drugs