Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Complicated Intra-abdominal Infections (IGNITE1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01844856
First received: April 29, 2013
Last updated: February 29, 2016
Last verified: February 2016
  Purpose
This is a Phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy, safety, and pharmacokinetics of eravacycline compared with ertapenem in the treatment of adult complicated intra-abdominal infections (cIAI).

Condition Intervention Phase
Complicated Intra-abdominal Infections
Drug: Eravacycline
Drug: Ertapenem
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of Eravacycline Compared With Ertapenem in Complicated Intra-abdominal Infections

Resource links provided by NLM:


Further study details as provided by Tetraphase Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Clinical Response of Eravacycline and Ertapenem Treatment Arms at the Test-of-cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population [ Time Frame: TOC visit: 25-31 days after the first dose of study drug ] [ Designated as safety issue: No ]
    Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection [cIAI], unplanned surgical procedures or percutaneous drainage procedures, persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (outcome was neither cure nor failure, or assessment was not available). Participants who were failures at the End-of-Treatment (EOT) visit (within 24 hours of last dose) were considered failures at the TOC visit. The number of participants with a clinical response classification of cure, failure, or indeterminate is presented.


Secondary Outcome Measures:
  • Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Modified Intent-to-treat (MITT) Population at the TOC Visit [ Time Frame: TOC visit: 25-31 days after first dose ] [ Designated as safety issue: No ]
    Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection [cIAI], unplanned surgical procedures or percutaneous drainage procedures, persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (outcome was neither cure nor failure, or assessment was not available). Participants who were failures at the EOT visit (within 24 hours of last dose) were considered failures at the TOC visit. The number of participants with a clinical response classification of cure, failure, or indeterminate is presented.

  • Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Clinically Evaluable (CE) Population at the TOC Visit [ Time Frame: TOC visit: 25-31 days after first dose ] [ Designated as safety issue: No ]
    Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection [cIAI], unplanned surgical procedures or percutaneous drainage procedures, persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (outcome was neither cure nor failure, or assessment was not available). Participants who were failures at the EOT visit (within 24 hours of last dose) were considered failures at the TOC visit. The number of participants with a clinical response classification of cure, failure, or indeterminate is presented.


Enrollment: 541
Study Start Date: August 2013
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eravacycline, 1.0 mg/kg q12h
Eravacycline was administered intravenously (IV) at a dose of 1.0 milligram per kilogram of body weight (mg/kg) every 12 hours (q12h) for a minimum of 4 days and a maximum of 14 days. Eravacycline treatment was to be stopped when symptoms of complicated intra-abdominal infection (cIAI) resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.
Drug: Eravacycline
Other Name: TP-434
Drug: Placebo
Administered IV to maintain the blind.
Active Comparator: Ertapenem, 1.0 g q24h
Ertapenem was administered IV at a dose of 1.0 gram (g) every 24 hours (q24h) for a minimum of 4 days and a maximum of 14 days. Ertapenem treatment was to be stopped when symptoms of cIAI resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.
Drug: Ertapenem
Other Name: Invanz
Drug: Placebo
Administered IV to maintain the blind.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participant hospitalized for cIAI
  2. At least 18 years of age (and not over 65 years of age for participant in India)
  3. Evidence of a systemic inflammatory response
  4. Abdominal pain or flank pain (with or without rebound tenderness), or pain caused by cIAI that is referred to another anatomic area
  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, 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 90 days following last study drug dose or practicing sexual abstinence

Exclusion Criteria:

  1. Unlikely to survive the 6-8 week study period
  2. Renal failure
  3. Presence or possible signs of hepatic disease
  4. Immunocompromised condition, including known human immunodeficiency virus (HIV) positivity (requiring anti-retroviral therapy or with CD4 count <300), acquired immune deficiency syndrome (AIDS), organ (bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroids (for example, >40 mg prednisone or equivalent per day for greater than 2 weeks)
  5. History of hypersensitivity reactions to tetracyclines, carbapenems, β-lactam antibiotics or to 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 disorder that may predispose to seizures or lower seizure threshold
  8. Previously received eravacycline in a clinical trial
  9. Antibiotic-related exclusions:

    1. Receipt of effective antibacterial drug therapy for cIAI for a continuous duration of >24 hours during the 72-hour preceding enrollment (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 ertapenem or any other carbapenem, or tigecycline for the current infection or
    3. 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 the previous 3 months or that is anticipated to begin prior to the Test-of-Cure (TOC) visit
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01844856

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Sponsors and Collaborators
Tetraphase Pharmaceuticals, Inc.
Investigators
Study Director: Patrick T. Horn, MD, PhD Tetraphase Pharmaceuticals, Inc.
  More Information

Responsible Party: Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01844856     History of Changes
Other Study ID Numbers: TP-434-008 
Study First Received: April 29, 2013
Results First Received: January 26, 2016
Last Updated: February 29, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Infection
Communicable Diseases
Intraabdominal Infections
Ertapenem
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 25, 2016