Delafloxacin IV and OS Administration Compared to Best Available Therapy in Patients With Surgical Site Infections

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of delafloxacin administered as IV and oral formulation in comparison with Best Available Therapy (BAT) in patients with superficial or deep incisional surgical site infection following a cardiothoracic/related leg or abdominal surgery.

Detailed Description
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This is a randomized, observer-blinded, active-controlled, parallel-group, multicenter, phase IIIb study for the treatment of incisional, superficial or deep, surgical site infection after cardiothoracic /related leg or abdominal surgery (i.e patients who are at risk of microbiologically resistant infections). IV to be switched to oral delafloxacin will be compared to treatments that represent the best available therapy (BAT) for either cardiothoracic/related leg or abdominal surgical site infection (SSI). Approximately 600 male and female eligible patients will be randomly assigned in a 1:1 ratio to receive delafloxacin or BAT. For patients who are randomised to BAT, the investigator will choose one out of two treatments available (two available for the cardiothoracic/related leg and two available for abdominal SSI) as most appropriate for patient characteristics and local epidemiological pattern. Duration of study depends on treatment duration (range: minimum 5 to maximum 14 days, as per Investigator's judgment) followed by visits up to 30 days after end of treatment. Patients will be hospitalized from Screening (within 30 days from surgery) and will remain hospitalized until considered improved or cure as per Investigator's judgment.

Official Title
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A Randomized, Observer-blinded, Active-controlled, Phase Illb Study to Compare IV / Oral Delafloxacin Fixed-dose Monotherapy With Best Available Treatments in a Microbiologically Enriched Population With Surgical Site Infections

Conditions
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Surgical Site Infection

Intervention / Treatment
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* Drug: Delafloxacin
* Drug: Vancomycin
* Drug: Linezolid
* Drug: Piperacillin/Tazobactam
* Drug: Tigecycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged more than 18 years. Patients with a history of cardiothoracic / related leg or abdominal surgery, occurred within 30 days and no implant is left in place, and a diagnosis of superficial or deep SSI according to the CDC definition. The severity of infection requires an IV treatment and patient hospitalization according to the Investigator's judgment. Exclusion Criteria: Previous IV antimicrobial therapy exceeding 24-hour duration during 72 hours prior to first dose. Any infection expected to require systemic antimicrobial agents other than study treatment(s). Medical history of significant hypersensitivity or allergic reaction or contraindication to the study drugs Medical history of central nervous system (CNS) disorders Medical history of myasthenia gravis. Medical history of C. difficile diarrhea. Organ-space infection. Complicated Intra-Abdominal Infection (cIAI) Chronic or underlying conditions at site of infection that may complicate the assessment of clinical response or would interfere with SSI healing. Underlying disease leading to deep immunosuppressive status. End-stage renal disease, CrCl <15 mL/min.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will compare delafloxacin against best available therapy selected by the investigator for the cardiothoracic/leg related or abdominal site infection
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delafloxacin<br>Delafloxacin IV, with the option to switch to delafloxacin oral | Drug: Delafloxacin<br>* Powder for solution for infusion 300 mg or tablet 450 mg, BID, for 5 to 14 days<br>|
| Active Comparator: Best Available Therapy<br>Cardiothoracic / related leg SSI Vancomycin IV Linezolid IV, with the option to switch to linezolid oral. In case of suspicion of Gram-negative, additional therapy shall be added as per investigator's choice Abdominal SSI Piperacillin/Tazobactam IV, OR Tigecycline IV In case of suspicion of MRSA, if the pre-selected treatment is Piperacillin/Tazobactam, additional therapy shall be added as per investigator's choice. | Drug: Vancomycin<br>* Powder for solution for infusion 15mg/kg, BID, for 5 to 14 days<br>Drug: Linezolid<br>* Solution for infusion or tablet, 600 mg BID, for 5 to 14 days<br>Drug: Piperacillin/Tazobactam<br>* Powder for solution for infusion 4/0.5 g, TID, for 5 to 14 days<br>Drug: Tigecycline<br>* Powder for solution for infusion 50 mg, TID, for 5 to 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Success at Test Of Cure Visit | Clinical Success defined as the clinical response of Cure or improved. Below the definitions: Cure: The complete resolution of all baseline signs and symptoms of SSI Improved: two or more signs and/or symptoms (but not all) were considered resolved thus the patient had improved to an extent that no additional antibiotic treatment was necessary. | 7-14 days after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Infection Related Length of Stay (IRLOS) | Length of Stay since beginning of therapy till patient stabilization and considered suitable for hospital discharge | up to 14 days | 
| Hospital Length of Stay (LOS) | Length of Stay since Screening till actual hospital discharge | up to 45 days (Late Follow Up visit) | 
| Number of Participants Eligible to Switch to Oral Formulation According to Blinded Observer's Assessment | Blinded assessment based on patient stabilization and ability to tolerate OS diet. In particular, the following details had to be met: Systolic blood pressure normal/not clinically significant abnormal No infection related tachycardia Afebrile status; body temperature <38°C for at least 24 hours* WBC count normalized/not clinically significant abnormal Patient able to tolerate PO diet/to take PO treatment and no GI absorption problem The measure counts only the participants eligible to switch, without taking into account the actually switched. Indeed, only linezolid in the BAT has an equivalent oral formulation suitable for the switch. | up to 14 days | 
| Microbiological Response | Documented or presumed eradication or persistence | up to 14 days (End Of Treatment visit) and 7-14 days after last dose (Test Of Cure visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infection, Surgical Infection