Clinical trial NCT01984684: Delafloxacin vs Vancomycin and Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Active Controlled Study to Evaluate the Efficacy + Safety of IV + Oral Delafloxacin Compared With Vancomycin + Aztreonam in Patients With Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Skin and Subcutaneous Tissue Bacterial Infections
Skin Structures and Soft Tissue Infections
Keywords: Bacterial skin infection
infection
skin
delafloxacin
vancomycin
aztreonam
methicillin-resistant Staphylococcus aureus (MRSA) bacteria
bacterial infection
Anti-Infective Agents
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-15
Enrollment: 850
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: The purpose of this study is to evaluate the effects of Delafloxacin versus Vancomycin plus Aztreonam in the treatment of patients with acute bacterial skin and soft tissue infections.

Detailed description: The purpose of this study is to determine if delafloxacin, an investigational drug, is safe and effective in the treatment of skin and nearby tissue infections compared with a combination of other antibiotics, vancomycin and aztreonam.

Eligibility criteria: Inclusion Criteria:

* Adult (≥ 18 years of age) men or women with a diagnosis of ABSSSI (cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection) with surrounding redness of a minimum surface area of 75 cm\^2 and at least two signs of systemic infection
* In the opinion of the investigator, the subject must require and be a suitable candidate for IV antibiotic therapy, and the subject must be able and willing to comply with protocol requirements

Exclusion Criteria:

* A medical history of significant hypersensitivity or allergic reaction to quinolones, beta-lactams, vancomycin, or vancomycin derivatives according to the judgment of the investigator.
* Women who are pregnant or lactating.
* Any chronic or underlying skin condition at the site of infection that may complicate the assessment of response, including infection involving a prosthetic joint, human or animal bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis, myositis, tendinitis, endocarditis, sustained shock, gangrene or gas gangrene; burns covering ≥10% of body surface area; severely compromised immune system, severely impaired arterial blood supply to an extremity with an ABSSSI, deep vein thrombosis or superficial thrombophlebitis, and requiring either an amputation or multiple debridement procedures.
* Receipt of systemic antibiotic therapy in the 14 days before enrollment unless 1 of the following was documented:

  * Received ≥ 48 hours of antibiotic therapy for ABSSSI AND clinical progression is documented (i.e., not by patient history alone).
  * Recently (within 14 days) completed a treatment course with an antibacterial drug for an infection other than ABSSSI and the drug does not have activity against bacterial pathogens that cause ABSSSI.
  * Received only 1 dose of either a single, potentially effective, short-acting antimicrobial drug or drug regimen for ABSSSI.
* Any underlying disease that, in the opinion of the investigator, could interfere with the subject's ability to participate in the study including severe cardiac disease, known history of liver disease, end-stage renal disease, malignancy, psychiatric disorder, ongoing treatment for seizures or untreated history of seizures, or life expectancy of \< 3 months.

Primary outcomes:
measure: Objective Response of ≥20% Reduction in Lesion Erythema Area Compared to Baseline at 48 to 72 Hours After Initiation of Treatment as Determined by Digital Measurements of the Leading Edge.
timeFrame: 48 to 72 hrs after starting treatment
Secondary outcomes:
measure: Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint)
timeFrame: Study Day 14 ± 1
measure: Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit
timeFrame: Study Day 21 to 28
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Melinta 303 Study Site
state: Alabama
city: Montgomery
country: United States
facility: Melinta 303 Study Site
state: Alabama
city: Anaheim
country: United States
facility: Melinta 303 Study Site
state: California
city: Chula Vista
country: United States
facility: Melinta 303 Study Site
state: California
city: La Mesa
country: United States
facility: Melinta 303 Study Site
state: California
city: Long Beach
country: United States
facility: Melinta 303 Study Site
state: California
city: Modesto
country: United States
facility: Melinta 303 Study Site
state: California
city: Oceanside
country: United States
facility: Melinta 303 Study Site
state: California
city: San Diego
country: United States
facility: Melinta 303 Study Site
state: California
city: Stockton
country: United States
facility: Melinta 303 Study Site
state: California
city: Torrance
country: United States
facility: Melinta 303 Study Site
state: California
city: DeLand
country: United States
facility: Melinta 303 Study Site
state: Florida
city: Orlando
country: United States
facility: Melinta 303 Study Site
state: Florida
city: Columbus
country: United States
facility: Melinta 303 Study Site
state: Georgia
city: Savannah
country: United States
facility: Melinta 303 Study Site
state: Georgia
city: Eunice
country: United States
facility: Melinta 303 Study Site
state: Louisiana
city: Springfield
country: United States
facility: Melinta 303 Study Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Melinta 303 Study Site
state: Minnesota
city: Butte
country: United States
facility: Melinta 303 Study Site
state: Montana
city: Lincoln
country: United States
facility: Melinta 303 Study Site
state: Nebraska
city: Las Vegas
country: United States
facility: Melinta 303 Study Site
state: Nevada
city: Somers Point
country: United States
facility: Melinta 303 Study Site
state: New Jersey
city: Teaneck
country: United States
facility: Melinta 303 Study Site
state: New Jersey
city: Columbus
country: United States
facility: Melinta 303 Study Site
state: Ohio
city: Toledo
country: United States
facility: Melinta 303 Study Site
state: Ohio
city: Rapid City
country: United States
facility: Melinta 303 Study Site
state: South Dakota
city: Jackson
country: United States
facility: Melinta 303 Study Site
state: Tennessee
city: Smyrna
country: United States
facility: Melinta 303 Study Site
state: Tennessee
city: Channelview
country: United States
facility: Melinta 303 Study Site
state: Texas
city: Houston
country: United States
facility: Melinta 303 Study Site
state: Texas
city: San Antonio
country: United States
facility: Melinta 303 Study Site
state: Texas
city: La Plata
country: Argentina
facility: Melinta 303 Study Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Melinta 303 Study Site
state: Santa Fe
city: Cordoba
country: Argentina
facility: Melinta 303 Study Site
city: Santa Fe
country: Argentina
facility: Melinta 303 Study Site
city: Salvador
country: Brazil
facility: Melinta 303 Study Site
state: Bahia
city: Belo Horizonte
country: Brazil
facility: Melinta 303 Study Site
state: Minas Gerais
city: Lavras
country: Brazil
facility: Melinta 303 Study Site
state: Minas Gerais
city: Passo Fundo
country: Brazil
facility: Melinta 303 Study Site
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Melinta 303 Study Site
state: Sao Paulo
city: São José Do Rio Preto
country: Brazil
facility: Melinta 303 Study Site
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Melinta 303 Study Site
city: Pleven
country: Bulgaria
facility: Melinta 303 Study Site
city: Plovdiv
country: Bulgaria
facility: Melinta 303 Study Site
city: Ruse
country: Bulgaria
facility: Melinta 303 Study Site
city: Sofia
country: Bulgaria
facility: Melinta 303 Study Site
city: Varna
country: Bulgaria
facility: Melinta 303 Study Site
city: Santiago
country: Chile
facility: Melinta 303 Study Site
city: Temuco
country: Chile
facility: Melinta 303 Study Site
city: Kohtla-Järve
country: Estonia
facility: Melinta 303 Study Site
city: Tallinn
country: Estonia
facility: Melinta 303 Study Site
city: Tartu
country: Estonia
facility: Melinta 303 Study Site
city: Voru
country: Estonia
facility: Melinta 303 Study Site
city: Batumi
country: Georgia
facility: Melinta 303 Study Site
city: Kutaisi
country: Georgia
facility: Melinta 303 Study Site
city: Tbilisi
country: Georgia
facility: Melinta 303 Study Site
city: Zugdidi
country: Georgia
facility: Melinta 303 Study Site
city: Kaposvar
country: Hungary
facility: Melinta 303 Study Site
city: Kecskemét
country: Hungary
facility: Melinta 303 Study Site
city: Nyiregyhaza
country: Hungary
facility: Melinta 303 Study Site
city: Szeged
country: Hungary
facility: Melinta 303 Study Site
city: Veszprem
country: Hungary
facility: Melinta 303 Study Site
city: Wŏnju
country: Korea, Republic of
facility: Melinta 303 Study Site
state: Gang'weondo
city: Ansan
country: Korea, Republic of
facility: Melinta 303 Study Site
state: Gyeonggido
city: Goyang
country: Korea, Republic of
facility: Melinta 303 Study Site
state: Gyeonggido
city: Daegu
country: Korea, Republic of
facility: Melinta 303 Study Site
city: Daejeon
country: Korea, Republic of
facility: Melinta 303 Study Site
city: Gwangju
country: Korea, Republic of
facility: Melinta 303 Study Site
city: Incheon
country: Korea, Republic of
facility: Melinta 303 Study Site
city: Seoul
country: Korea, Republic of
facility: Melinta 303 Study Site
city: Daugavpils
country: Latvia
facility: Melinta 303 Study Site
city: Liepaja
country: Latvia
facility: Melinta 303 Study Site
city: Rezekne
country: Latvia
facility: Melinta 303 Study Site
city: Riga
country: Latvia
facility: Melinta 303 Study Site
city: Guadalajara
country: Mexico
facility: Melinta 303 Study Site
state: Jalisco
city: Monterrey
country: Mexico
facility: Melinta 303 Study Site
state: Nuevo Leon
city: Chisinau
country: Moldova, Republic of
facility: Melinta 303 Study Site
city: Trujillo
country: Peru
facility: Melinta 303 Study Site
state: La Libertad
city: Cusco
country: Peru
facility: Melinta 303 Study Site
city: Lima
country: Peru
facility: Melinta 303 Study Site
city: Loreto
country: Peru
facility: Melinta 303 Study Site
city: Cluj-Napoca
country: Romania
facility: Melinta 303 Study Site
state: Cluj
city: Craiova
country: Romania
facility: Melinta 303 Study Site
state: Dolj
city: Timisoara
country: Romania
facility: Melinta 303 Study Site
state: Timis
city: Bucharest
country: Romania
facility: Melinta 303 Study Site
city: Targu mures
country: Romania
facility: Melinta 303 Study Site
city: Banska Bystrica
country: Slovakia
facility: Melinta 303 Study Site
city: Presov
country: Slovakia
facility: Melinta 303 Study Site
city: Kaohsiung
country: Taiwan
facility: Melinta 303 Study Site
city: New Taipei City
country: Taiwan
facility: Melinta 303 Study Site
city: Taichung
country: Taiwan
facility: Melinta 303 Study Site
city: Tainan City
country: Taiwan
facility: Melinta 303 Study Site
city: Taipei
country: Taiwan
facility: Melinta 303 Study Site
city: Zhonghe
country: Taiwan
facility: Melinta 303 Study Site
Study officials:
affiliation: Melinta Therapeutics, Inc.
name: Sue K Cammarata, MD
role: STUDY_DIRECTOR
References:
citation: Lodise T, Corey R, Hooper D, Cammarata S. Safety of Delafloxacin: Focus on Adverse Events of Special Interest. Open Forum Infect Dis. 2018 Sep 10;5(10):ofy220. doi: 10.1093/ofid/ofy220. eCollection 2018 Oct.
citation: O'Riordan W, McManus A, Teras J, Poromanski I, Cruz-Saldariagga M, Quintas M, Lawrence L, Liang S, Cammarata S; PROCEED Study Group. A Comparison of the Efficacy and Safety of Intravenous Followed by Oral Delafloxacin With Vancomycin Plus Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections: A Phase 3, Multinational, Double-Blind, Randomized Study. Clin Infect Dis. 2018 Aug 16;67(5):657-666. doi: 10.1093/cid/ciy165.
citation: McCurdy S, Lawrence L, Quintas M, Woosley L, Flamm R, Tseng C, Cammarata S. In Vitro Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00772-17. doi: 10.1128/AAC.00772-17. Print 2017 Sep.