Clinical trial NCT00431678: Efficacy and Safety of Sequential IV/PO Moxifloxacin in Comparison to IV Levofloxacin Plus IV Ceftriaxone Followed by PO Levofloxacin, in the Treatment of Patients With Community-acquired Pneumonia
Official title: A Multinational, Prospective, Randomized, Double-blind Study to Investigate the Efficacy and Safety of Sequential Intravenous/Oral Moxifloxacin in Comparison to Intravenous Levofloxacin Plus Intravenous Ceftriaxone Followed by Oral Levofloxacin, in the Treatment of Patients With Severe Community-acquired Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia
Keywords: Community-acquired Pneumonia
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2007-02-06
Enrollment: 738
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: Sequential therapy with intravenous to oral moxifloxacin, was tested at 69 study centres in 17 countries to determine if this treatment regimen is safe and effective in treating hospitalized adult patients with community-acquired pneumonia. 748 patients were participated in the study over an 18 months period. Individual patient involvement in the study was approximately 4-6 weeks. Moxifloxacin was compared to a combination treatment regimen of high dose intravenous ceftriaxone plus high dose intravenous levofloxacin followed by high dose oral levofloxacin.


Eligibility criteria: Inclusion Criteria:

* Patients aged 18 years or above
* All of the following signs and symptoms of pneumonia:

  * Fever (core/ rectal/ tympanic temperature \>/= 38.5°C or axillary/ oral/ cutaneous temperature \>/= 38.0°C) or hypothermia (core/ rectal/ tympanic temperature \</= 35.5°C or axillary/ oral/ cutaneous temperature \</= 35.0°C)
  * White blood cell (WBC) count \> 10,000/µL, or \>/= 15% immature neutrophils (bands), regardless of the peripheral WBC count, or total WBC count \< 4,500/µL
  * The presence of at least 2 of the following symptoms: - Cough- Purulent sputum production
* Dyspnoea or tachypnoea (respiratory rate \> 20 breaths/minute)
* Rigors and/or chills- Chest pain
* Auscultatory findings on pulmonary examination of rales/crackles and/or evidence of pulmonary consolidationAND
* Radiological evidence of (an) infiltrate(s) consistent with bacterial pneumonia at baseline or within 24 hours following enrolment
* Fine score \>/= 71 (i.e. Pneumonia PSI risk Class III, IV or V, requiring hospitalisation for the treatment of CAP)
* Written informed consent obtained from the patient or a next-of-kin

Exclusion Criteria:

* Known hypersensitivity to fluoroquinolones, or other quinolones, and/or to beta-lactams, or any of the excipients
* Female patients who are pregnant or lactating
* History of tendon disease/disorder related to quinolone treatment
* Known congenital or documented-acquired QT prolongation; concomitant use of drugs, reported to increase the QT interval; uncorrected hypokalaemia; clinically relevant bradycardia; clinically relevant heart failure with reduced left
* ventricular ejection fraction; previous history of symptomatic arrhythmias
* History of epilepsy- Known glucose-6-phosphate dehydrogenase deficiency
* Known severe impaired liver function (i.e. Child Pugh C), (refer to Section 10.4 for definition) or transaminases increase \> 5 fold ULN- Hospitalisation for \> 48 hours before developing pneumonia, or discharge from hospital \< 30 days prior- Systemic antibacterial therapy for more than 24 hours within 14 days of enrolment
* Patients requiring concomitant systemic antibacterial agents
* Known structural lung disease (e.g. cystic fibrosis, bronchiectasis, or lung cancer), or other known conditions (e.g. malnutrition) predisposing to infection with nosocomial-like organisms such as Pseudomonas aeruginosa
* Lung abscess, pleural empyema, risk factors for aspiration pneumonia (e.g. recent stroke, head injury, dementia)
* Known rapidly fatal underlying disease (death expected within 6 months)
* Known or suspected active tuberculosis or endemic fungal infection- Neutropenia (neutrophil count \< 1,000/µL) caused by immunosuppressive therapy or malignancy
* Patients known to have AIDS (CD4 count \< 200/µL) or HIV-seropositive patients receiving HAART
* Previous enrolment in this study
* Participation in any clinical investigational drug study within the previous 4 weeks
* Patient with pre-terminal renal failure (creatinine clearance \< 10 mL/min) and patients undergoing haemodialysis

Primary outcomes:
measure: Clinical response
timeFrame: 5 to 7 days after last dose of study medication
Secondary outcomes:
measure: Clinical and bacteriological response
timeFrame: At the day of switch from intravenous to oral therapy
measure: Clinical and bacteriological response on treatment
timeFrame: At day 3 to 5
measure: Clinical and bacteriological response
timeFrame: At the end of treatment
measure: Bacteriological response
timeFrame: 5-7 days after end of treatment
measure: Mortality attributable to pneumonia
timeFrame: 5-7 days after end of treatment
measure: Clinical and bacteriological response
timeFrame: At days 21 to 28 after end of treatment
measure: Symptoms course of community-acquired pneumonia
timeFrame: at defined visits
measure: Adverse Event Collection
timeFrame: all visits
Other outcomes:
Locations:
city: Vicente López
country: Argentina
state: Buenos Aires
city: Buenos Aires
country: Argentina
state: Capital Federal
city: Buenos Aires
country: Argentina
state: Capital Federal
city: Buenos Aires
country: Argentina
state: Capital Federal
city: Buenos Aires
country: Argentina
state: Capital Federal
city: Bruxelles - Brussel
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Namur
country: Belgium
city: Temuco
country: Chile
state: IX Region
city: Viña del Mar
country: Chile
state: V Region
city: Santiago de Chile
country: Chile
city: Santiago
country: Chile
city: Bogotá
country: Colombia
city: Bucaramanga
country: Colombia
city: Santafé de Bogotá
country: Colombia
city: Agen
country: France
city: Aix-en-provence
country: France
city: Argenteuil
country: France
city: Avignon
country: France
city: Belfort
country: France
city: Bordeaux
country: France
city: Brive-la-gaillarde
country: France
city: Paris
country: France
city: Saint-gaudens
country: France
city: Toulon
country: France
city: Vesoul
country: France
city: Bochum
country: Germany
state: Nordrhein-Westfalen
city: Bochum
country: Germany
state: Nordrhein-Westfalen
city: Lüdenscheid
country: Germany
state: Nordrhein-Westfalen
city: Paderborn
country: Germany
state: Nordrhein-Westfalen
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Rio
country: Greece
state: Patras
city: Athens
country: Greece
city: Thessaloniki
country: Greece
city: Afula
country: Israel
city: Ashkelon
country: Israel
city: Holon
country: Israel
city: Tel Aviv
country: Israel
city: Tel Hashomer
country: Israel
city: Kaunas
country: Lithuania
city: Kaunas
country: Lithuania
city: Vilnius
country: Lithuania
city: Vilnius
country: Lithuania
city: Toluca
country: Mexico
state: Edo. de México
city: Guadalajara
country: Mexico
state: Jalisco
city: Monterrey
country: Mexico
state: Nuevo León
city: México, D.F.
country: Mexico
city: México, D.F.
country: Mexico
city: México, D.F.
country: Mexico
city: México, D.F.
country: Mexico
city: Eindhoven
country: Netherlands
state: Noord Brabant
city: Den Bosch
country: Netherlands
city: EDE
country: Netherlands
city: Harderwijk
country: Netherlands
city: Heerlen
country: Netherlands
city: Callao
country: Peru
city: Lima Cercado
country: Peru
city: Lima
country: Peru
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Lisboa
country: Portugal
city: Bloemfontein
country: South Africa
state: Free State
city: Bloemfontein
country: South Africa
state: Freestate
city: Brits
country: South Africa
state: Gauteng
city: Johannesburg
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Cape Town
country: South Africa
state: Western Cape
city: Somerset West
country: South Africa
state: Western Cape
city: Huesca
country: Spain
state: Aragón
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Alcalá de Henares
country: Spain
state: Madrid
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Guadalajara
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Jönköping
country: Sweden
city: Kalmar
country: Sweden
city: Karlstad
country: Sweden
city: Skövde
country: Sweden
city: Middlesborough
country: United Kingdom
state: Cleveland
city: Dumfries
country: United Kingdom
state: Dumfries and Galloway
city: Hull
country: United Kingdom
state: Humberside
city: Edinburgh
country: United Kingdom
state: Lothian
city: Rotherham
country: United Kingdom
state: South Yorkshire
city: Sheffield
country: United Kingdom
state: South Yorkshire
city: Newcastle Upon Tyne
country: United Kingdom
state: Tyne and Wear
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Torres A, Garau J, Arvis P, Carlet J, Choudhri S, Kureishi A, Le Berre MA, Lode H, Winter J, Read RC; MOTIV (MOxifloxacin Treatment IV) Study Group. Moxifloxacin monotherapy is effective in hospitalized patients with community-acquired pneumonia: the MOTIV study--a randomized clinical trial. Clin Infect Dis. 2008 May 15;46(10):1499-509. doi: 10.1086/587519.