Moxifloxacin Versus Amoxicillin Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT00656747

Collaborator

(none)

1,372

Enrollment

221

Locations

Arms

Duration (Months)

6.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study to assess the safety and efficacy of moxifloxacin compared to that of amoxicillin-clavulanic acid for the treatment of subjects with acute exacerbation of chronic bronchitis.

Condition or Disease	Intervention/Treatment	Phase
Chronic Bronchitis	Drug: Avelox (Moxifloxacin, BAY12-8039) Drug: Amoxicillin clavulanic acid	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

1372 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

MAESTRAL - A Prospective, Multinational, Multicenter, Randomized, Double Blind, Double Dummy, Controlled Study Comparing the Efficacy and Safety of Moxifloxacin to That of Amoxicillin Clavulanic Acid for the Treatment of Subjects With Acute Exacerbations of Chronic Bronchitis.

Study Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 2	Drug: Amoxicillin clavulanic acid Subjects will be randomised to amoxicillin-clavulanic acid 875/125 mg PO BID (7 days). Subjects will also take placebo tablets, so that each subject takes 3 tablets per day for 7 days. Prior to randomization, subjects are stratified based on co-administration of short-course systemic steroids.
Experimental: Arm 1	Drug: Avelox (Moxifloxacin, BAY12-8039) Subjects will be randomised to moxifloxacin 400 mg PO OD (5 days). Subjects will also take placebo tablets, so that each subject takes 3 tablets per day for 7 days. Prior to randomization, subjects are stratified based on co-administration of short-course systemic steroids.

Arm

Intervention/Treatment

Active Comparator: Arm 2

Drug: Amoxicillin clavulanic acid

Subjects will be randomised to amoxicillin-clavulanic acid 875/125 mg PO BID (7 days). Subjects will also take placebo tablets, so that each subject takes 3 tablets per day for 7 days. Prior to randomization, subjects are stratified based on co-administration of short-course systemic steroids.

Experimental: Arm 1

Drug: Avelox (Moxifloxacin, BAY12-8039)

Subjects will be randomised to moxifloxacin 400 mg PO OD (5 days). Subjects will also take placebo tablets, so that each subject takes 3 tablets per day for 7 days. Prior to randomization, subjects are stratified based on co-administration of short-course systemic steroids.

Outcome Measures

Primary Outcome Measures

Clinical failure at 8 weeks post therapy [At day 63]

Secondary Outcome Measures

Clinical failure rates [Through to day 35]
Bacteriological eradication rates [Through to day 63]
Clinical failure rates for subjects with positive sputum culture at enrollment [Through to day 63]
Weekly mean symptom scores measured by the AECB SS [Through to day 63]
Rates and speed of symptom relief measured by the AECB SS [Through to day 63]
Clinical failure rates for subjects with co-administration of systemic corticosteroids (stratum 1) [Through to day 63]
Clinical failure rates for subjects without co-administration of systemic corticosteroids (stratum 2) [Through to day 63]
Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators [Through to day 63]
Improvement in symptoms burden measured by the AECB SS [Through to day 63]
Improvement in health related QoL measured by the SGRQ [Through to day 63]
spirometry tests will be compared between treatment groups [Through to day 63]
HCRU relat. to chronic bronchitis management incl. rescue med., concomitant med., therap. adjuncts, diagn. procedures, other medical care/medical staff requirement, hospitalizations (incl. ward and duration), and work productivity and activity impairment [Through to day 63]
Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea [Through to day 63]

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Outpatients with chronic bronchitis
Male or female subjects, >=60 years old
Post bronchodilator forced expiratory volume in one second (FEV1) less than or equal to 60% predicted and FEV1 / forced vital capacity (FVC) less than 70% at enrollment
Documented history of 2 or more AECB episodes, within 12 months of study enrollment, requiring a course of systemic antibiotics and/or systemic corticosteroids
All symptoms/signs must be present and confirmed by the Investigator:
increase in dyspnea
purulent sputum
increase in sputum volume
Current or past cigarette smoker with equal to or greater than 20 pack year smoking history
Subjects must be exacerbation free for at least 30 days prior to enrollment
Subjects must be willing and able to complete the questionnaires and subject booklet without assistance

Exclusion Criteria:

Known hypersensitivity to quinolones, ß lactams, or to any of the excipients of the study drugs
Known to have congenital or acquired QT prolongation
Known to have clinically relevant bradycardia
Known to have clinically relevant heart failure with reduced left ventricular ejection fraction
Known to have previous history of symptomatic arrhythmias
Taking QT prolonging drugs, for example Class Ia or III antiarrhythmic agents or other QT prolonging drugs
Known electrolyte disturbances that are not controlled, particularly uncorrected hypokalemia
Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose galactose malabsorption
History of a tendon disease/disorder
Known history of liver dysfunction (Child-Pugh C), including known elevated transaminase levels (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] >5 times the upper limit of normal [5 x ULN])
Known severe renal impairment with glomerular filtration rate of <30 mL/min
Known neutropenia (neutrophil count <1000/mm3) caused by immunosuppressive therapy or malignancy
Known to have Acquired Immunodeficiency Syndrome (AIDS) (CD4 count of <200/mm3), or be human immunodeficiency virus (HIV) positive and receiving highly active anti retroviral therapy (HAART) (testing for HIV is not mandatory)
Known chronic asthma (>15% reversibility or at least 200 mL), bronchial carcinoma, active pulmonary tuberculosis, known diffuse bronchiectasis, cystic fibrosis, or pneumonia (a chest x ray is not mandatory)
Known history of chronic colonization of pathogenic organisms resistant to moxifloxacin and/or amoxicillin clavulanic acid (eg, P. aeruginosa, methicillin resistant Staphylococcus aureus)
Receiving long term (>4 consecutive weeks) systemic corticosteroid treatment (>10 mg/day of prednisolone or equivalent)
Received short course of systemic corticosteroid treatment within 30 days prior to enrollment
Life expectancy of less than 6 months
Receiving systemic antibacterial therapy within 30 days prior to study enrollment
Requiring concomitant systemic antibacterial agents
Requiring home ventilatory support (subjects requiring home/portable oxygen therapy or continuous positive airway pressure (CPAP) for sleep apnea are not excluded) and/or those who have a tracheotomy in situ
History of liver function disorders following previous treatment with amoxicillin-clavulanic acid
Receiving disulfiram therapy

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Escaldes - Engordany		Andorra
2	Florencio Varela	Buenos Aires	Argentina
3	Quilmes	Buenos Aires	Argentina
4	Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	1426
5	Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	C1424BSF
6	Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina	C1425AWC
7	Buenos Aires	Ciudad Auton. de Buenos Aires	Argentina
8	San Miguel de Tucumán	Tucuman	Argentina	4000
9	San Miguel de Tucumán	Tucuman	Argentina
10	Vicente López		Argentina	1638
11	Concord	New South Wales	Australia	2139
12	Brisbane	Queensland	Australia	4101
13	Adelaide	South Australia	Australia	5041
14	Woodville	South Australia	Australia	5011
15	Nedlands	Western Australia	Australia	6009
16	Aalst		Belgium	9300
17	Antwerpen		Belgium	2018
18	Bruxelles - Brussel		Belgium	1020
19	Halen		Belgium	3545
20	Lommel		Belgium	3920
21	Moerkerke		Belgium	8340
22	Namur		Belgium	5000
23	Yvoir		Belgium	5530
24	Juiz de Fora	Minas Gerais	Brazil	36036-110
25	Porto Alegre	Rio Grande do Sul	Brazil	90610-000
26	São Paulo	Sao Paulo	Brazil	04032-060
27	São Paulo	Sao Paulo	Brazil	05403-900
28	Calgary	Alberta	Canada	T2N 4Z6
29	Edmonton	Alberta	Canada	T6G 2B7
30	Edmonton	Alberta	Canada	T6L 5X8
31	Kelowna	British Columbia	Canada	V1Y 8E7
32	Vancouver	British Columbia	Canada	V5Z 4E1
33	Winnipeg	Manitoba	Canada	R3A 1R8
34	Winnipeg	Manitoba	Canada	R3C 0N2
35	Saint John	New Brunswick	Canada	E2K 2T8
36	Saint John	New Brunswick	Canada	E2M 3W5
37	Antigonish	Nova Scotia	Canada	B2G 2C2
38	Sydney Mines	Nova Scotia	Canada	B1V 2Y5
39	Burlington	Ontario	Canada	L7R 3X4
40	Hamilton	Ontario	Canada	L8N 4A6
41	London	Ontario	Canada	N6A 4V2
42	London	Ontario	Canada	N6A 5G6
43	Toronto	Ontario	Canada	M6H 3M2
44	Longueuil	Quebec	Canada	J4N 1E1
45	Montreal	Quebec	Canada	H2L 4M1
46	Sherbrooke	Quebec	Canada	JIH 4J6
47	Santiago		Chile
48	Valparaíso		Chile
49	Viña del Mar		Chile
50	Guangzhou	Guangdong	China	510120
51	Guangzhou	Guangdong	China	510405
52	Changsha	Hunan	China	410013
53	Shengyang	Liaoning	China	110004
54	Shenyang	Liaoning	China	110001
55	Chengdu	Sichuan	China	610041
56	Beijing		China	100020
57	Beijing		China	100050
58	Shanghai		China	200003
59	Shanghai		China	200040
60	Shanghai		China	200233
61	Tianjin		China	300052
62	Cali	Cauca	Colombia
63	Bogotá		Colombia
64	Bucaramanga		Colombia
65	Cali		Colombia
66	Medellín		Colombia
67	Santafe de Bogotá		Colombia
68	Osijek		Croatia	310 00
69	Petrinja		Croatia	44 250
70	Rijeka		Croatia	510 00
71	Zagreb		Croatia	10000
72	Kyjov		Czech Republic	697 01
73	Lovosice		Czech Republic	410 02
74	Neratovice		Czech Republic	227 11
75	Pardubice - Trnova		Czech Republic	530 09
76	Praha - Malesice		Czech Republic	108 00
77	Praha - Troja		Czech Republic	182 00
78	Marseille		France	13009
79	Mont-de-marsan		France	40000
80	Nice		France	06000
81	Perpignan		France	66025
82	Bad Dürrheim	Baden-Württemberg	Germany	78073
83	Augsburg	Bayern	Germany	86150
84	Cottbus	Brandenburg	Germany	03050
85	Rüdersdorf	Brandenburg	Germany	15562
86	Zossen	Brandenburg	Germany	15806
87	Frankfurt	Hessen	Germany	60318
88	Frankfurt	Hessen	Germany	60389
89	Fulda	Hessen	Germany	36039
90	Neubrandenburg	Mecklenburg-Vorpommern	Germany	17033
91	Lüdenscheid	Nordrhein-Westfalen	Germany	58515
92	Neuwied	Rheinland-Pfalz	Germany	56564
93	Böhlen	Sachsen	Germany	04564
94	Delitzsch	Sachsen	Germany	04509
95	Dresden	Sachsen	Germany	01307
96	Leipzig	Sachsen	Germany	04207
97	Leipzig	Sachsen	Germany	04275
98	Leipzig	Sachsen	Germany	04357
99	Meißen	Sachsen	Germany	01662
100	Bad Segeberg	Schleswig-Holstein	Germany	23795
101	Lübeck	Schleswig-Holstein	Germany	23552
102	Berlin		Germany	10365
103	Berlin		Germany	10717
104	Berlin		Germany	10969
105	Berlin		Germany	12043
106	Berlin		Germany	12203
107	Berlin		Germany	13597
108	Berlin		Germany	14059
109	Hamburg		Germany	20354
110	Hamburg		Germany	22305
111	Athens	Attica	Greece	106 76
112	Mezourlo	Larissa	Greece	41110
113	Rio	Patras	Greece	265 04
114	Athens		Greece	11527
115	Ioannina		Greece	45500
116	HongKong		Hong Kong
117	Kowloon		Hong Kong
118	Bandung		Indonesia
119	Jakarta		Indonesia	13230
120	Surabaya		Indonesia
121	Killarney	Kerry	Ireland
122	Enniscorthy	Wexford	Ireland
123	Gorey	Wexford	Ireland
124	Bray	Wicklow	Ireland
125	Longford		Ireland
126	Pregiato di Cava dei Tirreni	Salerno	Italy	84013
127	Busto Arsizio	Varese	Italy	21052
128	Bussolengo	Verona	Italy	37012
129	Ascoli Piceno		Italy	63100
130	Catania		Italy	95122
131	Chieti		Italy	66100
132	Milano		Italy	20123
133	Milano		Italy	20157
134	Perugia		Italy	06156
135	Kraslava		Latvia	5601
136	Riga		Latvia	1009
137	Riga		Latvia	1011
138	Riga		Latvia	1050
139	Talsu		Latvia	3201
140	Valmiera		Latvia	4201
141	Ventspils		Latvia	LV-3601
142	Kaunas		Lithuania	LT-50425
143	Kaunas		Lithuania
144	Klaipeda		Lithuania	LT-94231
145	Siauliai		Lithuania	76231
146	Vilnius		Lithuania	LT-06122
147	Vilnius		Lithuania	LT-07156
148	Guadalajara	Jalisco	Mexico	44280
149	Huixquilucan	México	Mexico	CP 52763
150	Monterrey	Nuevo Leon	Mexico	64718
151	Monterrey	Nuevo Leon	Mexico	66480
152	Mérida	Yucatán	Mexico	97001
153	Chihuahua		Mexico	31350
154	Zacatecas		Mexico	98608
155	Eindhoven	Noord-Brabant	Netherlands	5623 EJ
156	Heerlen		Netherlands	6419 PC
157	Hoofddorp		Netherlands	2134 TM
158	Meppel		Netherlands	7943 KA
159	Utrecht		Netherlands	3582 KE
160	Karachi	Sindh	Pakistan	74800
161	Islamabad		Pakistan
162	Karachi		Pakistan	75500
163	Callao		Peru	CALLAO 2
164	Lima		Peru	31
165	Lima		Peru	33
166	Lima		Peru	LIMA 18
167	Lima		Peru	LIMA 27
168	Lima		Peru
169	Manila		Philippines
170	Quezon City		Philippines
171	Torres Vedras	Lisboa	Portugal	2560-324
172	Matosinhos	Porto	Portugal	4454-509
173	Vila Nova de Gaia	Porto	Portugal	4434-502
174	Coimbra		Portugal	3000-075
175	Lisboa		Portugal	1169-024
176	Lisboa		Portugal	1649-035
177	Porto		Portugal	4200
178	S. Martinho do Bispo		Portugal	3041-856
179	Santarém		Portugal	2005-177
180	Port Elizabeth	Eastern Cape	South Africa	6014
181	Bloemfontein	Freestate	South Africa	9324
182	Benoni	Gauteng	South Africa	1500
183	Centurion	Gauteng	South Africa	0140
184	Kempton Park	Gauteng	South Africa	1610
185	Pretoria	Gauteng	South Africa	0002
186	Pretoria	Gauteng	South Africa	0084
187	Pretoria	Gauteng	South Africa
188	Durban	KwaZulu Natal	South Africa	4037
189	Durban	KwaZulu Natal	South Africa	4091
190	Thabazimbi	Limpopo	South Africa	0380
191	Witbank	Mpumalanga	South Africa	1035
192	Cape Town	Western Cape	South Africa	7505
193	Paarl	Western Cape	South Africa	7647
194	Somerset West	Western Cape	South Africa	7130
195	Badalona	Barcelona	Spain	08916
196	Sant Boi de Llobregat	Barcelona	Spain	08830
197	Palma de Mallorca	Illes Baleares	Spain	07010
198	Requena	Valencia	Spain	46340
199	Barcelona		Spain	08034
200	Barcelona		Spain	08036
201	Guadalajara		Spain	19002
202	Madrid		Spain	28040
203	Aarau	Aargau	Switzerland	5000
204	Laufen	Basel-Landschaft	Switzerland	4242
205	Oberwil	Basel-Landschaft	Switzerland	4104
206	Binningen	Basel-Stadt	Switzerland	4102
207	Basel		Switzerland	4031
208	Bern		Switzerland	3004
209	Thun		Switzerland	3600
210	Wettingen		Switzerland	5430
211	Zürich		Switzerland	8048
212	Zürich		Switzerland	8091
213	Bangkok		Thailand	10330
214	Chiang Mai		Thailand	50200
215	Nonthaburi		Thailand	11000
216	Glasgow	Stratchclyde	United Kingdom	G3 8YJ
217	Glasgow	Stratchclyde	United Kingdom	G45 9AW
218	Glasgow	Stratchclyde	United Kingdom	G46 8NY
219	Glasgow	Stratchclyde	United Kingdom	G69 7AD
220	Glasgow	Stratchclyde	United Kingdom
221	Coventry	Warwickshire	United Kingdom	CV7 8LA