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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT00431678

Collaborator

(none)

738

Enrollment

Locations

Arms

Duration (Months)

7.6

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Avelox (Moxifloxacin, BAY12-8039) Drug: Levofloxacin + Ceftriaxone	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

738 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2004

Actual Primary Completion Date :

Jul 1, 2005

Actual Study Completion Date :

Jul 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1	Drug: Avelox (Moxifloxacin, BAY12-8039) Sequential intravenous/oral (400/400 mg once daily for 7 to 14 days) of Avelox (Moxifloxacin, BAY12-8039)
Active Comparator: Arm 2	Drug: Levofloxacin + Ceftriaxone Intravenous combination therapy of levofloxacin 500 mg twice daily and ceftriaxone (2 g once a day) followed by oral levofloxacin (500 mg twice a day for 7 to 14 days).

Arm

Intervention/Treatment

Experimental: Arm 1

Drug: Avelox (Moxifloxacin, BAY12-8039)

Sequential intravenous/oral (400/400 mg once daily for 7 to 14 days) of Avelox (Moxifloxacin, BAY12-8039)

Active Comparator: Arm 2

Drug: Levofloxacin + Ceftriaxone

Intravenous combination therapy of levofloxacin 500 mg twice daily and ceftriaxone (2 g once a day) followed by oral levofloxacin (500 mg twice a day for 7 to 14 days).

Outcome Measures

Primary Outcome Measures

Clinical response [5 to 7 days after last dose of study medication]

Secondary Outcome Measures

Clinical and bacteriological response [At the day of switch from intravenous to oral therapy]
Clinical and bacteriological response on treatment [At day 3 to 5]
Clinical and bacteriological response [At the end of treatment]
Bacteriological response [5-7 days after end of treatment]
Mortality attributable to pneumonia [5-7 days after end of treatment]
Clinical and bacteriological response [At days 21 to 28 after end of treatment]
Symptoms course of community-acquired pneumonia [at defined visits]
Adverse Event Collection [all visits]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Vicente López	Buenos Aires	Argentina	B1602DOH
2	Buenos Aires	Capital Federal	Argentina	C1118AAT
3	Buenos Aires	Capital Federal	Argentina	C1120AAF
4	Buenos Aires	Capital Federal	Argentina	C1180AAX
5	Buenos Aires	Capital Federal	Argentina	C1431FWO
6	Bruxelles - Brussel		Belgium	1070
7	Bruxelles - Brussel		Belgium	1200
8	Leuven		Belgium	3000
9	Liege		Belgium	4000
10	Namur		Belgium	5000
11	Temuco	IX Region	Chile
12	Viña del Mar	V Region	Chile
13	Santiago de Chile		Chile
14	Santiago		Chile
15	Bogotá		Colombia
16	Bucaramanga		Colombia
17	Santafé de Bogotá		Colombia
18	Agen		France	47923
19	Aix-en-provence		France	13616
20	Argenteuil		France	95107
21	Avignon		France	84000
22	Belfort		France	90016
23	Bordeaux		France	33000
24	Brive-la-gaillarde		France	19100
25	Paris		France	75014
26	Saint-gaudens		France	31806
27	Toulon		France	83056
28	Vesoul		France	70014
29	Bochum	Nordrhein-Westfalen	Germany	44789
30	Bochum	Nordrhein-Westfalen	Germany	44791
31	Lüdenscheid	Nordrhein-Westfalen	Germany	58515
32	Paderborn	Nordrhein-Westfalen	Germany	33098
33	Halle	Sachsen-Anhalt	Germany	06112
34	Magdeburg	Sachsen-Anhalt	Germany	39112
35	Berlin		Germany	10117
36	Berlin		Germany	13353
37	Rio	Patras	Greece	265 04
38	Athens		Greece	11527
39	Thessaloniki		Greece	546 36
40	Afula		Israel	18101
41	Ashkelon		Israel	78306
42	Holon		Israel	58100
43	Tel Aviv		Israel	64239
44	Tel Hashomer		Israel	52621
45	Kaunas		Lithuania	45130
46	Kaunas		Lithuania	47144
47	Vilnius		Lithuania	LT-2001
48	Vilnius		Lithuania	LT-2006
49	Toluca	Edo. de México	Mexico	50130
50	Guadalajara	Jalisco	Mexico	44280
51	Monterrey	Nuevo León	Mexico	64460
52	México, D.F.		Mexico	02290
53	México, D.F.		Mexico	07760
54	México, D.F.		Mexico	14000
55	México, D.F.		Mexico	14080
56	Eindhoven	Noord Brabant	Netherlands	5623 EJ
57	Den Bosch		Netherlands	5211 RB
58	EDE		Netherlands	6716 RP
59	Harderwijk		Netherlands	3844 DG
60	Heerlen		Netherlands	6419 PC
61	Callao		Peru	02
62	Lima Cercado		Peru	LIMA 1
63	Lima		Peru	01
64	Bydgoszcz		Poland	85-326
65	Gdansk		Poland	80-803
66	Krakow		Poland	30-501
67	Lodz		Poland	91-425
68	Warszawa		Poland	00-909
69	Warszawa		Poland	01-138
70	Wroclaw		Poland	50-417
71	Lisboa		Portugal	1769-001
72	Bloemfontein	Free State	South Africa
73	Bloemfontein	Freestate	South Africa	9300
74	Brits	Gauteng	South Africa	0250
75	Johannesburg	Gauteng	South Africa	2132
76	Pretoria	Gauteng	South Africa	0083
77	Cape Town	Western Cape	South Africa
78	Somerset West	Western Cape	South Africa	7130
79	Huesca	Aragón	Spain	22004
80	L'Hospitalet de Llobregat	Barcelona	Spain	08907
81	Alcalá de Henares	Madrid	Spain	28805
82	Barcelona		Spain	08003
83	Barcelona		Spain	08036
84	Guadalajara		Spain	19002
85	Madrid		Spain	28008
86	Valencia		Spain	46014
87	Jönköping		Sweden	551 85
88	Kalmar		Sweden	391 85
89	Karlstad		Sweden	651 85
90	Skövde		Sweden	541 85
91	Middlesborough	Cleveland	United Kingdom	TS4 3BW
92	Dumfries	Dumfries and Galloway	United Kingdom	DG1 4EP
93	Hull	Humberside	United Kingdom	HU3 2JZ
94	Edinburgh	Lothian	United Kingdom	EH4 2XU
95	Rotherham	South Yorkshire	United Kingdom	S60 2UD
96	Sheffield	South Yorkshire	United Kingdom	S10 2JF
97	Newcastle Upon Tyne	Tyne and Wear	United Kingdom	NE7 7DN