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

A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of Eravacycline Compared With Meropenem in Complicated Intra-abdominal Infections

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).

Study Overview

• Status: Completed
• Conditions: Complicated Appendicitis; Complicated Intra-abdominal Infections
• Intervention / Treatment: Drug: Placebo; Drug: Eravacycline; Drug: Meropenem

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria
  • Plovdiv, Bulgaria
  • Ruse, Bulgaria
  • Sofia, Bulgaria
  • Varna, Bulgaria
• Czechia
  • Jihlava, Czechia
  • Kladno, Czechia
  • Kolin, Czechia
  • Prague, Czechia
• Estonia
  • Tallinn, Estonia
  • Tartu, Estonia
  • Viljandi, Estonia
  • Voru, Estonia
• Georgia
  • Batumi, Georgia
  • Kutaisi, Georgia
  • Tbilisi, Georgia
  • Zugdidi, Georgia
• Hungary
  • Gyor, Hungary
  • Kaposvar, Hungary
  • Pecs, Hungary
  • Veszprem, Hungary
• Latvia
  • Daugavpils, Latvia
  • Liepaja, Latvia
  • Rezekne, Latvia
  • Riga, Latvia
• Lithuania
  • Kaunas, Lithuania
  • Klaipeda, Lithuania
  • Vilnius, Lithuania
• Romania
  • Bucharest, Romania
  • Cluj-Napoca, Romania
  • Craiova, Romania
  • Targu Mures, Romania
  • Timisoara, Romania
• Russian Federation
  • Arkhangelsk, Russian Federation
  • Kaluga, Russian Federation
  • Krasnodar, Russian Federation
  • Nizhny Novgorod, Russian Federation
  • St. Petersburg, Russian Federation
  • Volgograd, Russian Federation
  • Vsevolozhsk, Russian Federation
• Ukraine
  • Dnipro, Ukraine
  • Ivano-Frankivsk, Ukraine
  • Kharkiv, Ukraine
  • Kyiv, Ukraine
  • Lviv, Ukraine
  • Odesa, Ukraine
  • Uzhhorod, Ukraine
  • Vinnytsia, Ukraine
• United States
  • California
    • Los Angeles, California, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • Somers Point, New Jersey, United States
  • Ohio
    • Cleveland, Ohio, United States
    • Columbus, Ohio, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Meropenem	Drug: Placebo; Drug: Meropenem; Other Names: Merrem
Experimental: Eravacycline	Drug: Placebo; Drug: Eravacycline; Other Names: TP-434

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population	Clinical cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no additional antibacterial therapy, surgical, or radiological intervention was required. Clinical failure was defined as death related to complicated intra-abdominal infection (cIAI), persistence of clinical symptoms of cIAI, unplanned surgical or percutaneous drainage procedures for complication or recurrence of cIAI, post-surgical wound infections requiring systemic antibiotics, or initiation of rescue antibacterial drug therapy for treatment of cIAI. Indeterminate/missing was defined as an outcome that was neither a clinical cure nor clinical failure, if the investigator did not complete an assessment, if a study visit was not conducted, or if the subject died for a cause unrelated to cIAI.	TOC visit: 25-31 days after first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the All-Treated (MITT) Population	Clinical cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no additional antibacterial therapy, surgical, or radiological intervention was required. Clinical failure was defined as death related to complicated intra-abdominal infection (cIAI), persistence of clinical symptoms of cIAI, unplanned surgical or percutaneous drainage procedures for complication or recurrence of cIAI, post-surgical wound infections requiring systemic antibiotics, or initiation of rescue antibacterial drug therapy for treatment of cIAI. Indeterminate/missing was defined as an outcome that was neither a clinical cure nor clinical failure, if the investigator did not complete an assessment, if a study visit was not conducted, or if the subject died for a cause unrelated to cIAI.	TOC visit: 25-31 days after first dose of study drug
Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population	Clinical cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no additional antibacterial therapy, surgical, or radiological intervention was required. Clinical failure was defined as death related to complicated intra-abdominal infection (cIAI), persistence of clinical symptoms of cIAI, unplanned surgical or percutaneous drainage procedures for complication or recurrence of cIAI, post-surgical wound infections requiring systemic antibiotics, or initiation of rescue antibacterial drug therapy for treatment of cIAI.	TOC visit: 25-31 days after first dose of study drug

Collaborators and Investigators

• Sponsor: Tetraphase Pharmaceuticals, Inc.
• Investigators: Study Director: Chief Medical Officer, Tetraphase Pharmaceuticals

Publications and helpful links

General Publications

• Solomkin JS, Gardovskis J, Lawrence K, Montravers P, Sway A, Evans D, Tsai L. IGNITE4: Results of a Phase 3, Randomized, Multicenter, Prospective Trial of Eravacycline vs Meropenem in the Treatment of Complicated Intraabdominal Infections. Clin Infect Dis. 2019 Aug 30;69(6):921-929. doi: 10.1093/cid/ciy1029.
• Solomkin JS, Sway A, Lawrence K, Olesky M, Izmailyan S, Tsai L. Eravacycline: a new treatment option for complicated intra-abdominal infections in the age of multidrug resistance. Future Microbiol. 2019 Oct;14:1293-1308. doi: 10.2217/fmb-2019-0135. Epub 2019 Oct 1.

Helpful Links

• IGNITE4: Results of a Phase 3, Randomized, Multicenter, Prospective Trial of Eravacycline vs. Meropenem in the Treatment of Complicated Intra-Abdominal Infections

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2016
• Primary Completion (Actual): May 8, 2017
• Study Completion (Actual): May 19, 2017

Study Registration Dates

• First Submitted: May 23, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (Estimate): May 27, 2016

Study Record Updates

• Last Update Posted (Actual): January 6, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Infections; Communicable Diseases; Intraabdominal Infections; Appendicitis; Anti-Infective Agents; Anti-Bacterial Agents; Meropenem
• Other Study ID Numbers: TP-434-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided