Trial Outcomes & Findings for A Trial To Evaluate Two Antibiotics For The Treatment Of Acute Exacerbation Of Chronic Bronchitis (AECB) (NCT NCT00254566)

NCT ID: NCT00254566

Last Updated: 2009-11-11

Results Overview

Cure=Signs\&symptoms(S\&S) of infection return to normal baseline level or clin improvement requiring no other antibiotics(AB); Failure=other AB due to S\&S of acute infection persisted/worsened,new clinical S\&S of acute infection,or clinical/radiological evidence of pneumonia developed during treatment; percent = # of cure or failure/total # of sub

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 398 participants
• Primary outcome timeframe: Test of Cure (TOC) Visit (Day 12-19)
• Results posted on: 2009-11-11

Participant Flow

398 subjects were enrolled and 396 subjects received treatment. Two subjects who were assigned to moxifloxacin did not receive at least one dose of treatment.

Participant milestones

Measure	Azithromycin Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Overall Study STARTED	198	198
Overall Study COMPLETED	167	172
Overall Study NOT COMPLETED	31	26

Reasons for withdrawal

Measure	Azithromycin Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Overall Study Death	1	0
Overall Study Adverse Event	5	4
Overall Study Lack of Efficacy	12	9
Overall Study Other	1	5
Overall Study Withdrawal by Subject	5	6
Overall Study Lost to Follow-up	7	2

Baseline Characteristics

A Trial To Evaluate Two Antibiotics For The Treatment Of Acute Exacerbation Of Chronic Bronchitis (AECB)

Baseline characteristics by cohort

Measure	Azithromycin n=198 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=198 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.	Total n=396 Participants Total of all reporting groups
Age Continuous	66.7 years STANDARD_DEVIATION 8.7 • n=93 Participants	67.5 years STANDARD_DEVIATION 8.5 • n=4 Participants	67.1 years STANDARD_DEVIATION 8.6 • n=27 Participants
Sex: Female, Male Female	18 Participants n=93 Participants	21 Participants n=4 Participants	39.0 Participants n=27 Participants
Sex: Female, Male Male	180 Participants n=93 Participants	177 Participants n=4 Participants	357.0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Clinical Per Protocol-all randomized subjects who were clinically eligible; received at least 80% of study med; no concomitant systemic antibiotics with activity against Acute Exacerbation of Chronic Bronchitis (AECB) pathogens, assessment made in appropriate visit window.

Cure=Signs&symptoms(S&S) of infection return to normal baseline level or clin improvement requiring no other antibiotics(AB); Failure=other AB due to S&S of acute infection persisted/worsened,new clinical S&S of acute infection,or clinical/radiological evidence of pneumonia developed during treatment; percent = # of cure or failure/total # of sub

Outcome measures

Measure	Azithromycin n=187 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=191 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Percentage of Clinical Cure (Success) at Test of Cure Visit(Clinical Per Protocol Population) Cure	93.0 percent	94.2 percent
Percentage of Clinical Cure (Success) at Test of Cure Visit(Clinical Per Protocol Population) Failure	7.0 percent	5.8 percent

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Full Analysis Set (FAS) is all randomized subjects who received at least 1 dose of study medication.

Clinical response (Cure vs Failure) at the TOC visit for the Full Analysis Set (FAS), Cure=Signs&symptoms(S&S) of infection return to normal baseline level or clin improvement requiring no other antibiotics(AB); Failure=other AB due to S&S of acute infection persisted/worsened,new clinical S&S of acute infection,or clinical/radiological evidence of pneumonia developed during treatment; percent = # of cure or failure/total # of sub

Outcome measures

Measure	Azithromycin n=198 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=198 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Percentage of Clinical Cure (Success) at Test of Cure Visit (Full Analysis Set) Cure	88.4 Percent	90.9 Percent
Percentage of Clinical Cure (Success) at Test of Cure Visit (Full Analysis Set) Failure	11.6 Percent	9.1 Percent

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Clinically eligible compromised of subjects from FAS with diagnosis of chronic bronchitis, clinical evidence of AECB based on S\&S, \& a neg chest radiograph for pneumonia based on radiologist opinion

Clinical Response at TOC Visit for clinically Eligible Subjects, Cure=Signs&symptoms(S&S) of infection return to normal baseline level or clin improvement requiring no other antibiotics(AB); Failure=other AB due to S&S of acute infection persisted/worsened,new clinical S&S of acute infection,or clinical/radiological evidence of pneumonia developed during treatment; percent = # of cure or failure/total # of sub

Outcome measures

Measure	Azithromycin n=198 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=198 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Percentage of Clinical Cure (Success)at Test of Cure Visit(Clinically Eligible Set) Cure	88.4 Percent	90.9 Percent
Percentage of Clinical Cure (Success)at Test of Cure Visit(Clinically Eligible Set) Failure	11.6 Percent	9.1 Percent

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Bacteriologic per protocol set is compromised of subjects from the Clinical Per Protocol set with a baseline bacterial pathogen. The number of participants is the number of unique pathogens identified at baseline.

Bacteriogical response assessed on per pathogen basis for Bacteriologic Per Protcol (BPP) set at TOC Visit. If no repeat culture, response is presumed from sponsor assessment of clinical response. Eradication =# of pathogens eradicated at TOC/N; Persistence =# of pathogens persistent at TOC/N; N=# of unique pathogens identified at baseline

Outcome measures

Measure	Azithromycin n=175 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=180 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Percentage of Bacteriologic Response at Test of Cure Visit Eradication	96 Percent	96.7 Percent
Percentage of Bacteriologic Response at Test of Cure Visit Persistence	4 Percent	3.3 Percent

SECONDARY outcome

Timeframe: Number of Days

Population: Time to AECB recurrence will be analyzed for the FAS using survival analysis methods to account for censored observations. Subjects are censored at the date last known to have not experienced a recurrence. Median time to recurrence will be estimated using the Kaplan-Meier method.

Subject is considered to have AECB recurrence if they had a clinical response of cure at the TOC visit and then met the definition of AECB during the follow-up period.

Outcome measures

Measure	Azithromycin n=175 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=180 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Time Taken for First Quartile (25%) of Subjects to Have AECB Recurrence	152 Days	204 Days

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Analysis on Full Analysis Set, Last Observation Carried Forward (LOCF)-missing values at TOC visit will be imputed by carrying forward the last post-baseline observation; total score calculated by deriving the simple average of relevant items, total score is set to missing if 1 or more domain scales cannot be derived.

CCQ was developed to measure health status of Chronic obstructive pulmonary disease (COPD) subjects. 10 items divided into 3 domains: symtoms, functional state, and mental state. Subject record their experiences during last 24 hrs. 7 pt scale - 0=asymptomatic and 6=extremely symptomatic/totally limited; change=mean score at observation minus mean score at baseline

Outcome measures

Measure	Azithromycin n=198 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=198 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Change From Baseline in Clinical COPD Questionnaire(CCQ)Total Score	-0.76 Score on Scale Standard Error 0.112	-0.71 Score on Scale Standard Error 0.106

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Analysis on Full Analysis Set, LOCF - missing values at the TOC visit will be imputed by carrying forward the last post baseline observation. Domain score is calculated by deriving the simple average of the relevant items, at least 75% of items must be non-missing to derive the domain score

1 of 3 domains that combined into the CCQ Total score. Items 1,2,5,and 6 address symptoms. Subject record their experiences during last 24 hrs. 7 pt scale - 0=asymptomatic and 6=extremely symptomatic; change=mean score at observation minus mean score at baseline

Outcome measures

Measure	Azithromycin n=198 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=198 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Change From Baseline in Clinical COPD Questionnaire(CCQ)Symptoms Score	-0.99 Score on Scale Standard Error 0.129	-0.96 Score on Scale Standard Error 0.122

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Analysis on Full Analysis Set, LOCF-missing values at the TOC visit will be imputed by carrying forward the last post baseline observation. Domain score is calculated by deriving the simple average of the relevant items, at least 75% of items must be non-missing to derive the domain score

1 of 3 domains that combined into the CCQ Total score. Items 7,8,9, and 10 address functional state. Subject record their experiences during last 24 hrs. 7 pt scale - 0=asymptomatic and 6=extremely; change=mean score at observation minus mean score at baseline

Outcome measures

Measure	Azithromycin n=198 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=198 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Change From Baseline in Clinical COPD Questionnaire(CCQ)Functional State Score	-0.61 Score on Scale Standard Error 0.127	-0.52 Score on Scale Standard Error 0.120

SECONDARY outcome

Timeframe: Test of Cure (TOC) Visit (Day 12-19)

Population: Analysis on Full Analysis Set, LOCF-missing values at TOC will be imputed by carrying forward the last post-baseline observation; Domain score is calculated by deriving the simple average of the relevant items, both mental state items must be non-missing to derive a mental state score

1 of 3 domains that combined into the CCQ Total score. Items 3 and 4 address mental state. Subject record their experiences during last 24 hrs. 7 pt scale - 0=asymptomatic and 6=extremely; change=mean score at observation minus mean score at baseline

Outcome measures

Measure	Azithromycin n=198 Participants Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin n=198 Participants Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Change From Baseline in Clinical COPD Questionnaire(CCQ)Mental State Score	-0.60 Score on Scale Standard Error 0.142	-0.54 Score on Scale Standard Error 0.134

Adverse Events

Azithromycin

Serious events: 4 serious events

Other events: 32 other events

Deaths: 0 deaths

Moxifloxacin

Serious events: 9 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Azithromycin Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Cardiac disorders Acute coronary syndrome	0.00% 0/198	0.51% 1/198
Infections and infestations Bronchitis	0.51% 1/198	0.51% 1/198
Infections and infestations Pneumonia	0.00% 0/198	0.51% 1/198
Infections and infestations Urinary tract infection	0.00% 0/198	0.51% 1/198
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.51% 1/198	2.0% 4/198
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/198	1.0% 2/198
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.51% 1/198	0.51% 1/198
Nervous system disorders Hypoxic Encephalopathy	0.51% 1/198	0.00% 0/198
General disorders Sudden Death	0.51% 1/198	0.00% 0/198
Infections and infestations Lung Infection	0.51% 1/198	0.00% 0/198
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.51% 1/198	0.00% 0/198

Other adverse events

Measure	Azithromycin Azithromycin SR (2.0 grams, microspheres formulation) was administered orally as single dose in form of an oral suspension on Day 1	Moxifloxacin Moxifloxican (400 milligrams)were administered orally as capsules once daily for five days.
Gastrointestinal disorders Abdominal pain	2.0% 4/198	0.51% 1/198
Gastrointestinal disorders Abdominal pain upper	2.0% 4/198	0.51% 1/198
Gastrointestinal disorders Diarrhea	9.1% 18/198	2.0% 4/198
Gastrointestinal disorders Nausea	0.51% 1/198	2.0% 4/198
Infections and infestations Nasopharyngitis	0.51% 1/198	3.0% 6/198
Investigations Alanine aminotransferase increased	2.0% 4/198	0.51% 1/198
Investigations Aspartate aminotransferase increased	2.0% 4/198	0.00% 0/198
Nervous system disorders Dizziness	0.51% 1/198	3.0% 6/198

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \<60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \<12 mo from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
• Publication restrictions are in place

Restriction type: OTHER