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

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

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.

Study Overview

• Status: Terminated
• Conditions: Surgical Site Infection
• Intervention / Treatment: Drug: Delafloxacin; Drug: Vancomycin; Drug: Linezolid; Drug: Piperacillin/Tazobactam; Drug: Tigecycline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy
    • Hospital Agostino Gemelli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delafloxacin; Delafloxacin IV, with the option to switch to delafloxacin oral	Drug: Delafloxacin; Powder for solution for infusion 300 mg or tablet 450 mg, BID, for 5 to 14 days
Active Comparator: Best Available Therapy; 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; Powder for solution for infusion 15mg/kg, BID, for 5 to 14 days; Drug: Linezolid; Solution for infusion or tablet, 600 mg BID, for 5 to 14 days; Drug: Piperacillin/Tazobactam; Powder for solution for infusion 4/0.5 g, TID, for 5 to 14 days; Drug: Tigecycline; Powder for solution for infusion 50 mg, TID, for 5 to 14 days

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Menarini Group
• Investigators: Principal Investigator: Stefano Margaritora, Hospital Agostino Gemelli

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2019
• Primary Completion (Actual): October 7, 2020
• Study Completion (Actual): October 28, 2020

Study Registration Dates

• First Submitted: July 29, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: January 25, 2022
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Infection, Surgical Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Wound Infection; Infections; Communicable Diseases; Surgical Wound Infection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; beta-Lactamase Inhibitors; Vancomycin; Linezolid; Tigecycline; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: DELA-01; 2018-001082-17 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes