Trial Outcomes & Findings for A Trial Comparing Moxifloxacin Versus Levofloxacin Plus Metronidazole In Uncomplicated Pelvic Inflammatory Disease (NCT NCT00453349)

NCT ID: NCT00453349

Last Updated: 2014-09-08

Results Overview

Clinical cure was defined as: Reduction of the tenderness score (modified McCormack) by \> 70% and apyrexia (rectal/tympanic/oral temperature value \< 38.0°C or axillary temperature value \< 37.5°C) and white blood cell count \< 10,500/mm\^3.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 460 participants
• Primary outcome timeframe: 7 - 14 days after completion of study drug therapy
• Results posted on: 2014-09-08

Participant Flow

A total of 463 females with uncomplicated PID were enrolled on the basis of a complete evaluation (interview, medical history and physical examination and laboratory tests). 460 subjects were randomized, 412 completed study treatment (whole medication), and 384 subjects were valid for the primary efficacy analysis.

The efficacy results in ITT are consistent with those in PP, supporting that this is a non-inferiority study and the primary efficacy population was PP not ITT. 76 subjects were excluded from primary efficacy analysis mainly due to essential data missing or invalid, violation of inclusion/exclusion criteria and insufficient duration of therapy.

Participant milestones

Measure	Moxifloxacin Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Randomized STARTED	228	232
Randomized COMPLETED	203	209
Randomized NOT COMPLETED	25	23
Reaching of Primary Endpoint (TOC) STARTED	225	230
Reaching of Primary Endpoint (TOC) Valid for Primary Efficacy Analysis	194	190
Reaching of Primary Endpoint (TOC) COMPLETED	215	219
Reaching of Primary Endpoint (TOC) NOT COMPLETED	10	11
Completed Study STARTED	228	232
Completed Study Completed Study Treatment	203	209
Completed Study COMPLETED	201	198
Completed Study NOT COMPLETED	27	34

Reasons for withdrawal

Measure	Moxifloxacin Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Randomized Adverse Event	12	11
Randomized Lack of Efficacy	2	1
Randomized Lost to Follow-up	7	5
Randomized Protocol Violation	1	1
Randomized Withdrawal by Subject	3	5
Reaching of Primary Endpoint (TOC) Missing information	10	11
Completed Study Adverse Event	12	11
Completed Study Lack of Efficacy	2	1
Completed Study Lost to Follow-up	7	5
Completed Study Protocol Violation	1	1
Completed Study Withdrawal by Subject	3	5
Completed Study Lost to follow up after study treatment	2	11

Baseline Characteristics

A Trial Comparing Moxifloxacin Versus Levofloxacin Plus Metronidazole In Uncomplicated Pelvic Inflammatory Disease

Baseline characteristics by cohort

Measure	Moxifloxacin n=228 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=232 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days	Total n=460 Participants Total of all reporting groups
Age, Continuous	35.2 years STANDARD_DEVIATION 8.4 • n=5 Participants	35.4 years STANDARD_DEVIATION 8.7 • n=7 Participants	35.2 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	228 Participants n=5 Participants	232 Participants n=7 Participants	460 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Microbiology recovery	36 number of participants with pathogenes n=5 Participants	36 number of participants with pathogenes n=7 Participants	72 number of participants with pathogenes n=5 Participants
Total pelvic pain score (using modified McCormack score)	11.3 points on a scale STANDARD_DEVIATION 3.8 • n=5 Participants	11.6 points on a scale STANDARD_DEVIATION 3.8 • n=7 Participants	11.5 points on a scale STANDARD_DEVIATION 3.8 • n=5 Participants

PRIMARY outcome

Timeframe: 7 - 14 days after completion of study drug therapy

Population: The number of subjects in the PP population was slightly higher than the planned number of subjects (184 subjects per treatment group). The most common reasons for exclusion from the population valid for efficacy in both the Moxifloxacin and Comparator were essential data missing/invalid, followed by violation of inclusion/exclusion criteria.

Clinical cure was defined as: Reduction of the tenderness score (modified McCormack) by > 70% and apyrexia (rectal/tympanic/oral temperature value < 38.0°C or axillary temperature value < 37.5°C) and white blood cell count < 10,500/mm^3.

Outcome measures

Measure	Moxifloxacin n=194 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=190 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Clinical Response 7 to 14 Days After Completion of Study Drug Therapy in Per Protocol (PP) Population Clinical cure	152 participants	155 participants
Clinical Response 7 to 14 Days After Completion of Study Drug Therapy in Per Protocol (PP) Population Clinical non-success	42 participants	35 participants

SECONDARY outcome

Timeframe: 7 - 14 days after completion of study drug therapy

Population: Subjects who were randomized, had received at least one dose of study medication and had at least one observation after drug intake would be included in the ITT analysis.

For any subject in the ITT population also valid for the PP analysis, same clinical response as in the PP analysis was applied to the ITT analysis. For those subjects in the ITT population invalid for the PP analysis, any clinical response different from clinical cure was set to "non-success".

Outcome measures

Measure	Moxifloxacin n=225 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=230 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Clinical Response 7 to 14 Days After Completion of Study Drug Therapy on Intent To Treat (ITT) Population Clinical cure	163 participants	171 participants
Clinical Response 7 to 14 Days After Completion of Study Drug Therapy on Intent To Treat (ITT) Population Clinical non-success	62 participants	59 participants

SECONDARY outcome

Timeframe: 4 - 7 days after start of therapy

Population: Analysis was performed for the per protocol population.

At the During Therapy (Day 4 to 7) assessment, the clinical response was graded as clinical Improvement (severity score reduced by >30% with improvement in temperature, clinical failure (reduction in severity score of < or equal 30% and/or no improvement in temperature) or indeterminate (clinical assessment not possible to determine).

Outcome measures

Measure	Moxifloxacin n=188 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=186 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Clinical Response on Treatment for Per Protocol Population Clinical Improvement	177 participants	181 participants
Clinical Response on Treatment for Per Protocol Population Clinical failure	11 participants	5 participants

SECONDARY outcome

Timeframe: 4 - 7 days after start of therapy

Population: Subjects who were randomized, had received at least one dose of study medication and had at least one observation after drug intake would be included in the ITT analysis. For any subject in the ITT population also valid for the PP analysis, same clinical response as in the PP analysis was applied to the ITT analysis.

Clinical response during treatment was analyzed exploratively in the same way as the primary efficacy variable. At the During Therapy (Day 4 to 7) assessment, the clinical response was graded as clinical Improvement, clinical failure or indeterminate accordingly. Clinical improvement was considered success, all other outcomes as non-success.

Outcome measures

Measure	Moxifloxacin n=225 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=230 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Clinical Response on Treatment for Intent To Treat Population Failure, indeterminate, missing	59 participants	60 participants
Clinical Response on Treatment for Intent To Treat Population Clinical improvement	166 participants	170 participants

SECONDARY outcome

Timeframe: 7 - 14 days at TOC visit

Population: All subjects for whom a specific bacterial pathogen was isolated/identified from any pre-treatment culture and which was considered responsible for the infection would be assessed for bacteriological efficacy.

The bacteriological responses was based on the results of appropriate cultures taken before and, if necessary, during treatment, at the TOC visit and within the follow-up period. Bacteriological response at the TOC visit would also be based on repeated PCR tests for N. gonorrhoeae and C. trachomatis.

Outcome measures

Measure	Moxifloxacin n=30 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=26 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Bacteriological Response at Test Of Cure (TOC) Visit Microbiologically Valid Eradication	27 participants	22 participants
Bacteriological Response at Test Of Cure (TOC) Visit Microbiologically Valid Persistence	3 participants	4 participants

SECONDARY outcome

Timeframe: 7 - 14 days at TOC visit

Population: Patients were included in this analysis if a causative organism could be established pre-therapy by culture or PCR, and if the patient was valid for intent-to-treat.

Bacteriological response at the TOC was analyzed exploratively in the same way as the primary efficacy variable based on the subgroup of microbiologically valid subjects. At the TOC visit, eradication was considered a bacteriological success, and persistence, presumed persistence and superinfection were considered bacteriological failures.

Outcome measures

Measure	Moxifloxacin n=36 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=34 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Bacteriological Response at Test Of Cure (TOC) Visit in Intent To Treat Population With Causative Organism Eradication	28 participants	25 participants
Bacteriological Response at Test Of Cure (TOC) Visit in Intent To Treat Population With Causative Organism Persistence, indeterminate, missing	8 participants	9 participants

SECONDARY outcome

Timeframe: 28 - 42 days after completion of study drug therapy

Population: All successfully treated subjects and subjects evaluated as "indeterminate" at TOC, who were not administered an additional antibiotic therapy would have their clinical response rate assessed at the follow up visit. Patients with missing or indeterminate outcome were omitted.

Clinical response at follow up was analyzed exploratively in the same way as the primary efficacy variable. At Follow-up, the clinical response was graded as continued cure, clinical relapse, or indeterminate, of which only continued cure was considered success. Failures from end of treatment were carried forward.

Outcome measures

Measure	Moxifloxacin n=184 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=180 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Clinical Response at Follow-up Visit on Per Protocol Population Continued clinical cure	157 participants	158 participants
Clinical Response at Follow-up Visit on Per Protocol Population Continued failure, clinical recurrence/relapse	27 participants	22 participants

SECONDARY outcome

Timeframe: 28 - 42 days after completion of study drug therapy

Population: At the follow-up visit, the clinical response in subjects who were non-failures at the TOC visit were graded as Continued cure, Clinical relapse or Indeterminate.

All successfully treated subjects and subjects evaluated as"indeterminate" at TOC, who were not administered an additional antibiotic therapy would have their clinical response rate assessed at the follow-up visit. Patients with missing or indeterminate outcome were treated as non-successes.

Outcome measures

Measure	Moxifloxacin n=225 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=230 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Clinical Response at Follow-up Visit on Intent To Treat Population Continued clinical cure	166 participants	170 participants
Clinical Response at Follow-up Visit on Intent To Treat Population Failure, relapse, indeterminate, missing	59 participants	60 participants

SECONDARY outcome

Timeframe: 28 - 42 days after completion of study drug therapy

Population: At the follow-up visit, the bacteriological success response was classified as eradication, and recurrence/persistence as bacteriological failures.

Subjects with at least one causative organism identified in the pre-therapy culture or a positive pre-therapy PCR result and an appropriate post-therapy bacteriological evaluation available were analyzed. Bacteriological responses at follow-up visit was analyzed exploratively in the same way as the primary efficacy variable.

Outcome measures

Measure	Moxifloxacin n=28 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=26 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Bacteriological Response at Follow-up Visit Microbiologically Valid Eradication	23 participants	22 participants
Bacteriological Response at Follow-up Visit Microbiologically Valid Eradication with recurrence, persistence	5 participants	4 participants

SECONDARY outcome

Timeframe: 28 - 42 days after completion of study drug therapy

Population: At the follow-up visit, the bacteriological success response was classified as Eradication, and recurrence/persistence as bacteriological failures.

Subjects with at least one causative organism identified in the pre-therapy culture or a positive pre-therapy PCR result and an appropriate post-therapy bacteriological evaluation available were analyzed. Bacteriological responses at follow-up visit was analyzed exploratively in the same way as the primary efficacy variable.

Outcome measures

Measure	Moxifloxacin n=36 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=34 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Bacteriological Response at Follow-up Visit in Intent To Treat Population With Causative Organism Eradication	23 participants	23 participants
Bacteriological Response at Follow-up Visit in Intent To Treat Population With Causative Organism Eradication with recurrence, persistence	13 participants	11 participants

SECONDARY outcome

Timeframe: Up to 42 days after end of treatment

Population: The number of subjects who received alternative medicine in the PP population was analyzed. The clinical response was graded as alternative medicine (clinical cure, improvement, continued clinical cure) versus no alternative medicine.

As alternative medicine any systemic antibacterial medication was considered.

Outcome measures

Measure	Moxifloxacin n=194 Participants Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=190 Participants Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Number of Subjects Who Received Alternative Medicine Receiving alternative medicine	4 participants	1 participants
Number of Subjects Who Received Alternative Medicine Not receiving alternative medicine	190 participants	189 participants

Adverse Events

Moxifloxacin

Serious events: 3 serious events

Other events: 83 other events

Deaths: 0 deaths

Levofloxacin Plus Metronidazole

Serious events: 1 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Measure	Moxifloxacin n=225 participants at risk Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=230 participants at risk Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Gastrointestinal disorders Colitis	0.44% 1/225	0.00% 0/230
Infections and infestations Pyelonephrits acute	0.00% 0/225	0.43% 1/230
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.44% 1/225	0.00% 0/230
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.44% 1/225	0.00% 0/230

Other adverse events

Measure	Moxifloxacin n=225 participants at risk Moxifloxacin (Avelox, BAY12-8039) 400 mg by mouth (PO) once daily for 14 days	Levofloxacin Plus Metronidazole n=230 participants at risk Levofloxacin 500 mg by mouth (PO) once daily for 14 days plus Metronidazole 500 mg (PO) twice daily for 14 days
Gastrointestinal disorders Abdominal pain upper	4.4% 10/225	6.1% 14/230
Gastrointestinal disorders Nausea	19.1% 43/225	23.5% 54/230
Gastrointestinal disorders Vomiting	3.1% 7/225	6.5% 15/230
Nervous system disorders Dizziness	17.3% 39/225	15.7% 36/230
Psychiatric disorders Insomnia	3.1% 7/225	6.1% 14/230

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60