Trial Condition(s):

Abscess, Wound Infection, Diabetic Foot

Comparison of sequential IV/PO moxifloxacin with IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in patients with a complicated skin and skin structure infection

Bayer Identifier:

11974

ClinicalTrials.gov Identifier:

NCT00402727

EudraCT Number:

2006-001599-18

EU CT Number:

Not Available

Study Completed

Trial Purpose

Patients, who are considered suitable by their physicians to take part in this research, will have a physical examination (including an Electrocardiogram (ECG)), blood and urine samples taken, as well as a sample of the secretions or tissue around their infection site. In addition, the site of the infection will be photographed. The patients will be randomly assigned one of the treatments: intravenous (IV)/per oral (PO) moxifloxacin (drug under evaluation) or IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid (i.e., one of the reference treatments for this kind of infection). The maximum treatment duration will be 21 days, and the minimum will be 7 days. During the hospitalization, the patients will have a physical examination every day. On Day 3-5 during therapy as well as at the end of treatment, the patients will have repeated examinations. These tests and evaluations will be repeated 14 to 28 days after the end of treatment. During this visit, blood and urine samples will be taken only if judged necessary by the physicians.

Inclusion Criteria
- Written informed consent
 - Men or women of 18 years and above with a diagnosis of bacterial skin and skin structure infection that requires 
 -- Hospitalization and
 -- Initial parenteral therapy for at least 48 hours and
 -- Meets at least one of the following criteria:
 --- Involvement of deep soft tissue (e.g. fascial, muscle layers)
 --- Requirement for a significant surgical intervention including surgical drainage, drainage procedure guided by imaging and/or debridement
 --- Association with a significant underlying disease that may complicate response to treatment. An underlying disease is considered significant if it includes any of the following conditions that are present at the time of presentation: cancer (except basal- or squamous-cell cancer of the skin), cardiac (i.e., congestive heart disease), diabetes mellitus, hepatic (i.e., cirrhosis or another form of chronic liver disease), immunologic, renal disease, respiratory, transplantation or vascular disease
 - Duration of infection < 21 days
 - Diagnosis of one of the following skin and skin structure infections that requires hospitalization and initial parenteral antibiotic therapy for at least 48 hours:
 -- Major abscess(es) associated with extensive cellulitis, which requires antibiotic therapy in addition to surgical incision and drainage
 -- Diabetic foot infection of mild to severe intensity (perfusion, extent/size, depth/tissue loss, infection and sensation (PEDIS) grade 2-4) in the presence or absence of osteomyelitis. Subjects with osteomyelitis may only be enrolled if the infected bone is completely removed by surgery and if residual infection requiring antibiotics is still present following surgery
 -- Wound infection including: post surgical (surgical incision), post-traumatic, human bite/clenched fist and animal bite wound and wound associated with injection drug abuse:
 --- Infections must have occurred within 30 days of a surgical procedure, trauma, animal bite, or human bite, and involve the skin and skin structures at the site of the incision, trauma, or bite
 --- In addition, post-surgical/trauma wound infections must meet the following criteria:
 ---- Involvement of deep soft tissues (e.g. fascial and muscle layers) of the incision/trauma
 ---- At least one of the following criteria:
 ----- Purulent drainage from the deep incision/trauma
 ----- Identification of an infecting organism from an aseptically obtained culture of fluid or tissue from incision/trauma
 ---- At least one of the following signs and symptoms:
 ----- Localized pain or tenderness
 ----- Fever (see below) AND the incision (in case of post-surgical wound infections) is deliberately opened by a surgeon, unless the culture is negative
 ----- Abscess or other evidence of infection involving the deep incision/trauma, found on direct examination, during reoperation/operation (in case of trauma), or by histologic or radiologic examination
 ---- Diagnosis of a deep incisional/post-trauma Skin Structure Infections (SSI) by a surgeon or attending physician
 ---- Bite wounds/clenched fist infections and wounds associated with injection drug abuse must meet the criteria defining a Complicated Skin and Skin Structure Infections (cSSSI) 
 -- Infected ischemic ulcers with at least one of the following conditions:
 --- Peripheral vascular disease
 --- Conditions pre-disposing to pressure sores such as paraplegia, peripheral neuropathy
 --- Presence of at least 3 of the following signs or symptoms:
 ---- Purulent drainage or discharge
 ---- Erythema extending > 1 cm from the wound edge
 ---- Fluctuance
 ---- Pain or tenderness to palpation
 ---- Swelling or induration
 ---- Fever, defined as body temperature
 ----- > 37.5°C (axillary)
 ----- > 38°C (orally)
 ----- > 38.5°C (tympanically) or
 ----- > 39°C (rectally)
 ------ OR
 ----- Elevated total peripheral white blood cell (WBC) count > 12,000/mm3 or
 ----- >15 % immature neutrophils (bands) regardless of total peripheral WBC count
 ---- C reactive protein (CRP) >20 mg/L
 - Specimen obtained for culture from infected area by needle aspiration of obviously purulent material or by tissue biopsy or by curettage of the surface of ulcer within 48 hours prior to the initiation of study drug therapy
 - Duration of treatment of the skin/skin structure infection is anticipated to be at least 7 days.
 - Surgical drainage or debridement of infected wounds or abscesses, if necessary, have to have been completed <= 48 hours after the initiation of study drug therapy
Exclusion Criteria
- Women, who are pregnant or lactating, or in whom pregnancy can not be excluded (Note: a urine pregnancy test has to be performed for all women of childbearing potential before randomization to the study drug)
 - The following skin and skin structure infections:
 -- Necrotizing fasciitis including Fourniers gangrene, ecthyma gangrenosum, streptococcal necrotizing fasciitis and clostridial necrotizing fasciitis
 -- Burn wound infections
 -- Secondary infections of a chronic skin disease (e.g. atopic dermatitis)
 -- Infection of prosthetic materials (e.g. subcutaneous tissue infection related to a central venous catheter or permanent cardiac pacemaker battery pack). Subjects with removal of a prosthetic device involved in an infection should not be included
 -- Infections where a surgical procedure alone is definitive therapy
 -- Subjects with uncomplicated skin and skin structure infections including folliculitis and furunculosis, carbunculosis, simple abscesses and superficial cellulitis
 - Known hypersensitivity to quinolones and/or any type of beta-lactam antibiotic drugs or any of the excipients
 - Previous history of cholestatic jaundice/hepatic dysfunction associated with amoxicillin-clavulanic acid
 - Severe, life threatening disease with a life expectancy of less than 2 months
 - Immunosuppression including:
 -- Known neutropenia (neutrophil count < 1000/µL)
 -- Known lymphopenia with absolute CD4+ T cell count < 200/mm3
 -- Acquired immunodeficiency syndrome (AIDS)-defining event and/or concomitant therapy with Highly Active Antiretroviral Therapy (HAART)
 -- Chronic treatment (>/= 2 weeks) with known immunosuppressant therapy (including treatment with > 15 mg/day of systemic prednisone or equivalent)
 -- Any other congenital or acquired immune defect or immunosuppression
 - Known severe hepatic insufficiency (Child Pugh C) or transaminases increase > 5 fold upper limit of normal (ULN)
 - Known renal impairment with a baseline measured or calculated serum creatinine clearance < 40 mL/min
 - Known prolongation of the QT interval or concomitant use of drugs reported to increase the QT interval  (e.g. Class IA or Class III antiarrhythmics [eg., quinidine, procainamide, amiodarone, sotalol], neuroleptics [e.g. haloperidol], tricyclic antidepressive agents, certain antimicrobials [e.g. pentamidine, halofantrine], certain antihistaminics [e.g. terfenadine], and other [cisapride, vincamine IV, depridil, diphemanil])
 - Uncorrected hypokalemia
 - Clinically relevant bradycardia
 - Clinically relevant heart failure with reduced left ventricular ejection fraction (i.e., below 40%)
 - Previous history of symptomatic arrhythmias
 - Previous history of tendon disease/disorder with quinolones
 - Known or suspected concomitant bacterial infection requiring additional systemic antibacterial treatment, e.g. underlying septic arthritis
 - Requiring therapy with probenecid
 - Treatment with a systemic or topical antibacterial agent for > 24 hours in the previous 7 days preceding study entry unless the subject showed no response or had worsening of clinical signs and symptoms despite 3 or more days of prior therapy and a culture obtained at the time of subject enrollment showed persistence of a pathogen which is susceptible to the study drugs. The prior antimicrobial therapy must not have been a fluoroquinolone or a beta lactam/beta lactamase combination
 - Infection known to be due to a Methicillin-Resistant Staphylococcus Aureus (MRSA), Methicillin-Resistant Staphylococcus Epidermidis (MRSE) or Vancomycin Resistant Enterococcus (VRE) as the single isolated pathogen
 - Previous enrolment in this study
 - Participation in any clinical investigational drug study within 4 weeks of screening
 - Previous history of seizure disorders

Trial Summary

Enrollment Goal
813
Trial Dates
black-arrow
Phase
3
Could I receive a placebo?
No
Products
Avelox (Moxifloxacin hydrochloride, BAY12-8039)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
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Klinikum Mannheim gGmbH

Mannheim, Germany, 68135

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Universitätsklinikum Otto-von Guericke - Magdeburg

Magdeburg, Germany, 39120

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Universitätsklinikum Schleswig-Holstein / AÖR

Lübeck, Germany, 23538

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Universitätsklinikum Hamburg Eppendorf (UKE)

Hamburg, Germany, 20246

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Universitätsklinikum Münster

Münster, Germany, 48149

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Kliniken der Medizinischen Hochschule Hannover

Hannover, Germany, 30625

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Manchester Royal Infirmary

Manchester, United Kingdom, M13 9WL

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Royal Infirmary of Edinburgh

Edinburgh, United Kingdom, EH16 4SA

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Raigmore Hospital

Inverness, United Kingdom, IV2 3UJ

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Royal Hampshire County Hospital

Winchester, United Kingdom, SO22 5DG

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Hopital Beregovoy - Nevers

NEVERS, France, 58000

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Hopital Henri Duffaut - Avignon

AVIGNON, France, 84025

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Centre Hospitalier - Denain

DENAIN, France, 59220

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LE BOUCANET - LE GRAU DU ROI

LE GRAU DU ROI, France, 30240

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HSK, Dr.-Horst-Schmidt-Kliniken

Wiesbaden, Germany, 65191

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Klinikum Innenstadt der Ludwigs-Maximilians-Universität

München, Germany, 81377

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Klinikum Darmstadt

Darmstadt, Germany, 64297

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Johannes-Gutenberg-Universität Mainz

Mainz, Germany, 55101

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Ruhr-Universität-Bochum Medizinische Einrichtungen

Bochum, Germany, 44791

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Leeds General Infirmary

Leeds, United Kingdom, LS1 3EX

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Kings College Hospital

London, United Kingdom, SE5 9RS

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York General Hospital

York, United Kingdom, YO13 8HE

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Freeman Hospital

Newcastle Upon Tyne, United Kingdom, NE7 7DN

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Glasgow Royal Infirmary

Glasgow, United Kingdom, G4 0SF

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Raigmore Hospital

Inverness, United Kingdom, IV2 3UJ

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Centre Hospitalier de Cornouaille - Quimper

QUIMPER, France, 29000

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Centre Hospitalier

ANNECY, France, 74000

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Centre Hospitalier Universitaire - Grenoble

GRENOBLE, France, 38043

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Szpital Wojewodzki w Poznaniu

Poznan, Poland, 60-479

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Centralny Szpital Kliniczny AM

Warszawa, Poland, 02-097

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Szpital Uniwersytecki w Krakowie

Kraków, Poland, 30-501

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Samodzielny Publiczny Szpital Kliniczny nr 4

Lublin, Poland, 20-954

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SPSK nr 1

Lublin, Poland, 20-081

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SPZOZ Pulawy

Pulawy, Poland, 24-100

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IRCCS Policlinico San Matteo

Pavia, Italy, 27100

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Università G.D'Annunzio

Chieti, Italy, 66013

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Congregazione Figli Immacolata Concezione

Roma, Italy, 00167

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Hospital de la Mútua de Terrassa

Terrassa (Barcelona), Spain, 08221

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Hospital de la Santa Creu i de Sant Pau

Barcelona, Spain, 08025

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Hospital Central de Asturias

Oviedo, Spain, 33006

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Hospital General Universitario Gregorio Marañón

Madrid, Spain, 28007

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Hôpital Erasme/Erasmus Ziekenhuis

BRUXELLES - BRUSSEL, Belgium, 1070

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UZ Brussel

BRUXELLES - BRUSSEL, Belgium, 1090

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Sint-Jozefkliniek

BORNEM, Belgium, 2880

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Centre Hospitalier Général - Boulogne sur Mer

BOULOGNE SUR MER, France, 62321

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Centre Hospitalier Gustave Dron - Tourcoing

TOURCOING, France, 59280

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Wojewodzki Szpital Specjalistyczny im. S. Wyszynskiego SPZOZ

Lublin, Poland, 20-718

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A.O.U. Senese

Siena, Italy, 53100

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IRCCS Fond. Ca' Granda Ospedale Maggiore Policlinico

Milano, Italy, 20122

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Hospital Gómez Ulla

Madrid, Spain, 28047

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Hospital Clínic i Provincial de Barcelona

Barcelona, Spain, 08036

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Hospital Ramón y Cajal

Madrid, Spain, 28034

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Hospital General Universitario Gregorio Marañón

Madrid, Spain, 28007

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Hospital Clínico de Salamanca

Salamanca, Spain, 37007

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UZ Antwerpen

EDEGEM, Belgium, 2650

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Medisch Centrum Alkmaar

ALKMAAR, Netherlands, 1800 AM

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University of Cape Town

Cape Town, South Africa, 7925

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Sunninghill Hospital

Johannesburg, South Africa, 2157

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University of Stellenbosch

Cape Town, South Africa, 7505

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Chaim Sheba Medical Center

Tel Hashomer, Israel, 52621

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Maxima Medisch Centrum, locatie Eindhoven

EINDHOVEN, Netherlands, 5600 PD

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Pretoria Academic Hospital Ethics Committee

Pretoria, South Africa, 0084

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Pretoria Academic Hospital Ethics Committee

Pretoria, South Africa, 0084

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Tiervlei Trial Centre

Cape Town, South Africa, 7531

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Clinical Projects Research SA

Worcester, South Africa, 6850

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Rambam Medical Center

Haifa, Israel, 31096

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MHAT Russe

Ruse, Bulgaria, 7002

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MHATEM N.I. Pirogov

Sofia, Bulgaria, 1606

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Csolnoky Ferenc Veszprem County Hospital

Veszprem, Hungary, 8200

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Petz Aladar Megyei Korhaz

Györ, Hungary, 9024

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Budai Irgalmasrendi Hospital

Budapest, Hungary, 1027

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Laiko General Hospital of Athens

Athens, Greece, 11527

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AHEPA University General Hospital of Thessaloniki

Thessaloniki, Greece, 546 36

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Bureau of Medical Social Expertise

Moscow, Russia, 127486

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City Hospital No 14

St. Petersburg, Russia, 198099

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MBAL-Dobrich

Dobrich, Bulgaria, 9300

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Military Medical Academy

Sofia, Bulgaria, 1431

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UMHAT Dr. Georgi Stranski

Pleven, Bulgaria, 5800

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IV City Hospital-Sofia

Sofia, Bulgaria, 1606

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Alexandrovska UMHAT

Sofia, Bulgaria, 1431

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National Heart Hospital

Sofia, Bulgaria, 1309

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Allgemeines Krankenhaus der Stadt Wien Universitätskliniken

Wien, Austria, 1090

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Medizinische Universität Graz

Graz, Austria, 8036

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Medizinische Universität Graz

Graz, Austria, 8036

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Fejer megyei Szent Gyorgy Korhaz

Szekesfehervar, Hungary, 8000

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University of Debrecen Medical&Health Science Center

Debrecen, Hungary, 4032

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Somogy County Hospital "Kaposi Mor"

Kaposvar, Hungary, 7400

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University General Hospital of Patras

Rio Patras, Greece, 265 00

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Attikon University General Hospital of Attica

Athens, Greece, 124 62

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Evangelismos General Hospital of Athens

Athens, Greece, 106 76

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Clinical Hospital for Emergency Care n.a. N.V.Solovyov

Yaroslavl, Russia, 150003

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Moscow Scintific Clinical Institute named after Vladimirsky

Moscow, Russia, 129110

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Lviv Emergency Hospital

Lviv, Ukraine, 79659

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Central City Clinical Hospital

Kiev, Ukraine, 01023

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Regional Clinical Hospital

Ivano-Frankivsk, Ukraine, 76000

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Regional Clinical Hospital

Odessa, Ukraine, 65065

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Kaunas Medical University Hospital

Kaunas, Lithuania, LT-3007

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Siauliai County Hospital

Siauliai, Lithuania, LT-76231

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University Hospital of Vilnus City

Vilnius, Lithuania, 10207

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Latvian Maritime Medicine Center

Riga, Latvia, 1005

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Daugavpils Regional Hospital

Daugavpils, Latvia, LV-5417

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Sligo General Hospital

Sligo, Ireland

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Cork University Hospital

Wilton, Ireland

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Beaumont Hospital

Dublin, Ireland, 9

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St Vincents University Hospital

Dublin, Ireland, DUBLIN 4

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Dermato Venerology Clinical Hospital

Bucharest, Romania, 040215

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Laiko General Hospital of Athens

Athens, Greece, 115 27

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Scientific Research Institute for Traumatology and Orthopaed

Moscow, Russia, 197046

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Municipal Clinical Hospital N50

Moscow, Russia, 125206

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Central Clinical Hospital no 1 OAO RZD

Moscow, Russia, 123567

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Institute of Emergency Care n.a. Janelidze

St. Petersburg, Russia

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Smolensk Medical Academy

Smolensk, Russia, 214019

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City Clinical Hospital N 20

Moscow, Russia, 129327

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Main Military Clinical Hospital

Kiev, Ukraine, 01133

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City Hospital no 12

Kiev, Ukraine, 01103

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Uzhgorod Regional Hospital

Uzhgorod, Ukraine, 88018

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Military-Medical Dept. of Scurity Service

Kiev, Ukraine, 01021

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Ukmerge Hospital

Ukmerge, Lithuania, LT-20184

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Riga 2nd City Hospital

Riga, Latvia, 1002

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Paula Stradina Kliniskas Universitates slimnica

Riga, Latvia, 1002

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Valmiera Hospital

Valmiera, Latvia, LV-4201

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Riga Clinical Hospital "Gailezers"

Riga, Latvia, LV-1038

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Fundeni Clinical Institute

Bucharest, Romania, 022328

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Central Hospital of Liepaja

Liepaja, Latvia, LV 3400

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Mater Misericordiae University Hospital

Dublin, Ireland, 7

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University College Hospital

Galway, Ireland

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Clinical Emergency County Hospital

Cluj-Napoca, Romania, 400006

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"Sfantul Spiridon" Emergency Clinical County Hospital

Iasi, Romania, 700106

Locations

Spitatul Universitar de Urgenta Bucaresti

Bucharest, Romania, 050099

Trial Design