Clinical trial NCT01844856: Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Complicated Intra-abdominal Infections
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Complicated Intra-abdominal Infections
Lead sponsor: La Jolla Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2013-05-01
Enrollment: 541
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Clinical Response of Eravacycline and Ertapenem Treatment Arms at the Test-of-cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population
timeFrame: TOC visit: 25-31 days after the first dose of study drug
Secondary outcomes:
measure: Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Modified Intent-to-treat (MITT) Population at the TOC Visit
timeFrame: TOC visit: 25-31 days after first dose
measure: Clinical Response of Eravacycline and Ertapenem Treatment Arms in the Clinically Evaluable (CE) Population at the TOC Visit
timeFrame: TOC visit: 25-31 days after first dose
Other outcomes:
Locations:
city: Florence
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Glendale
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Torrance
country: United States
state: California
city: Aurora
country: United States
state: Illinois
city: Carmel
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: Camden
country: United States
state: New Jersey
city: Teaneck
country: United States
state: New Jersey
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Weston
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Cordoba
country: Argentina
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Rousse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Brno
country: Czechia
city: Kladno
country: Czechia
city: Melnik
country: Czechia
city: Olomouc
country: Czechia
city: Prague
country: Czechia
city: Usti nad Labem
country: Czechia
city: Kohtla-Jarve
country: Estonia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Paris
country: France
city: Heidelberg
country: Germany
city: Luebeck
country: Germany
city: Magdeburg
country: Germany
city: Daugavpils
country: Latvia
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Craiova
country: Romania
city: Timisoara
country: Romania
city: Kaluga
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Vsevolozhsk
country: Russian Federation
city: Benoni
country: South Africa
city: Johannesburg
country: South Africa
city: Pretoria
country: South Africa
city: Worcester
country: South Africa
city: Dnipropetrovsk
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Odesa
country: Ukraine
city: Uzhhorod
country: Ukraine
city: Zaporizhia
country: Ukraine
Study officials:
affiliation: Tetraphase Pharmaceuticals, Inc.
name: Patrick T Horn, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.