Clinical trial NCT02784704: Efficacy and Safety Study of Eravacycline Compared With Meropenem 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 Meropenem in Complicated Intra-abdominal Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Complicated Intra-abdominal Infections
Complicated Appendicitis
Lead sponsor: La Jolla Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2016-05-27
Enrollment: 500
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 (PK) of eravacycline compared with meropenem in the treatment of complicated intra-abdominal infections (cIAIs).


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Microbiological Intent-to-treat (Micro-ITT) Population
timeFrame: TOC visit: 25-31 days after first dose of study drug
Secondary outcomes:
measure: Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the All-Treated (MITT) Population
timeFrame: TOC visit: 25-31 days after first dose of study drug
measure: Number of Participants With a Favorable Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population
timeFrame: TOC visit: 25-31 days after first dose of study drug
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Indianapolis
country: United States
state: Indiana
city: Las Vegas
country: United States
state: Nevada
city: Somers Point
country: United States
state: New Jersey
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Jihlava
country: Czechia
city: Kladno
country: Czechia
city: Kolin
country: Czechia
city: Prague
country: Czechia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Viljandi
country: Estonia
city: Voru
country: Estonia
city: Batumi
country: Georgia
city: Kutaisi
country: Georgia
city: Tbilisi
country: Georgia
city: Zugdidi
country: Georgia
city: Gyor
country: Hungary
city: Kaposvar
country: Hungary
city: Pecs
country: Hungary
city: Veszprem
country: Hungary
city: Daugavpils
country: Latvia
city: Liepaja
country: Latvia
city: Rezekne
country: Latvia
city: Riga
country: Latvia
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Vilnius
country: Lithuania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Craiova
country: Romania
city: Targu Mures
country: Romania
city: Timisoara
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Kaluga
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Vsevolozhsk
country: Russian Federation
city: Dnipro
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Uzhhorod
country: Ukraine
city: Vinnytsia
country: Ukraine
Study officials:
affiliation: Tetraphase Pharmaceuticals
name: Chief Medical Officer
role: STUDY_DIRECTOR
References:
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 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.