Efficacy and Safety Study of Eravacycline Compared With Meropenem in Complicated Intra-abdominal Infections (IGNITE4)

Tetraphase Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Complicated Appendicitis; Complicated Intra-abdominal Infections

Treatments: Drug: Placebo; Drug: Eravacycline; Drug: Meropenem

Study type: Interventional

Funder types: Industry

Identifiers

NCT02784704

TP-434-025

Details and patient eligibility

About

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).

Enrollment: 500 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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500 participants in 2 patient groups

Eravacycline

Experimental group

Treatment:

Drug: Placebo

Drug: Eravacycline

Meropenem

Active Comparator group

Treatment:

Drug: Meropenem

Drug: Placebo