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

NCT01844856 | Completed Phase 3 Results

• 1 other identifier: TP-434-008
• Study Type: interventional
• Target: 541
• Locations: 13 countries
• Sites: 69

Brief Summary

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).

Conditions

Complicated Intra-abdominal Infections

Outcome Measures

Primary Outcomes (1)

• Clinical Response of Eravacycline and Ertapenem Treatment Arms at the Test-of-cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population

  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.

  TOC visit: 25-31 days after the first dose of study drug

Secondary Outcomes (2)

• Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Modified Intent-to-treat (MITT) Population at the TOC Visit

  TOC visit: 25-31 days after first dose

• Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Clinically Evaluable (CE) Population at the TOC Visit

  TOC visit: 25-31 days after first dose

Study Arms (2)

Eravacycline, 1.0 mg/kg q12h

EXPERIMENTAL

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; Drug: Placebo

Ertapenem, 1.0 g q24h

ACTIVE COMPARATOR

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; Drug: Placebo

Interventions

Eravacycline DRUG

Also known as: TP-434

Eravacycline, 1.0 mg/kg q12h

Ertapenem DRUG

Also known as: Invanz

Ertapenem, 1.0 g q24h

Placebo DRUG

Administered IV to maintain the blind.

Eravacycline, 1.0 mg/kg q12h; Ertapenem, 1.0 g q24h

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participant hospitalized for cIAI
• At least 18 years of age (and not over 65 years of age for participant in India)
• 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 90 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 90 days following last study drug dose or practicing sexual abstinence

You may not qualify if:

• Unlikely to survive the 6-8 week study period
• Renal failure
• Presence or possible signs of hepatic disease
• 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)
• History of hypersensitivity reactions to tetracyclines, carbapenems, β-lactam antibiotics or to 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 disorder that may predispose to seizures or lower seizure threshold
• Previously received eravacycline in a clinical trial
• 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
• Receipt of ertapenem or any other carbapenem, or tigecycline for the current infection or
• Need for concomitant systemic antimicrobial agents 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

Sponsors & Collaborators

• Tetraphase Pharmaceuticals, Inc: lead

Study Sites (69)

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Florence, Alabama, United States

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Mobile, Alabama, United States

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Glendale, California, United States

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La Mesa, California, United States

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Los Angeles, California, United States

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Torrance, California, United States

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Aurora, Illinois, United States

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Carmel, Indiana, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Minneapolis, Minnesota, United States

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Las Vegas, Nevada, United States

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Camden, New Jersey, United States

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Teaneck, New Jersey, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Weston, Ohio, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Córdoba, Argentina

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Brno, Czechia

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Kladno, Czechia

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Mělník, Czechia

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Olomouc, Czechia

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Prague, Czechia

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Ústí nad Labem, Czechia

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Kohtla-Järve, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Paris, France

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Heidelberg, Germany

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Lübeck, Germany

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Magdeburg, Germany

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Daugavpils, Latvia

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Liepāja, Latvia

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Riga, Latvia

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Šiauliai, Lithuania

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Vilnius, Lithuania

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Bucharest, Romania

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Cluj-Napoca, Romania

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Craiova, Romania

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Timișoara, Romania

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Kaluga, Russia

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Kemerovo, Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Saint Petersburg, Russia

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Smolensk, Russia

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Tomsk, Russia

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Volgograd, Russia

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Vsevolozhsk, Russia

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Benoni, South Africa

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Johannesburg, South Africa

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Pretoria, South Africa

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Worcester, South Africa

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Dnipropetrovsk, Ukraine

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Kyiv, Ukraine

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Odesa, Ukraine

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Uzhhorod, Ukraine

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Zaporizhia, Ukraine

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Related Publications (3)

• 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.

  PMID: 31570004 DERIVED

• 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.

  PMID: 30561562 DERIVED

• Solomkin J, Evans D, Slepavicius A, Lee P, Marsh A, Tsai L, Sutcliffe JA, Horn P. Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial: A Randomized Clinical Trial. JAMA Surg. 2017 Mar 1;152(3):224-232. doi: 10.1001/jamasurg.2016.4237.

  PMID: 27851857 DERIVED

MeSH Terms

Interventions

eravacycline; Ertapenem

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Development Officer
• Organization: La Jolla Pharmaceutical Company

ljpcregulatory@ljpc.com

+1.617.715.3600

Study Officials

• Patrick T Horn, MD, PhD

  Tetraphase Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 1, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: January 11, 2022
• Results First Posted: March 21, 2016

Record last verified: 2021-12

Locations

BU (5); FR (1); UA (7); LI (4); RO (4); ES (3); LA (3); DE (3); ZA (4); CZ (6); RU (9); AR (1); US (19)