Clinical Trial Results:
Multinational, Randomized, Double-Blind, Double-Dummy, Comparative Study to Evaluate the Efficacy and Safety of Telithromycin 25 mg/kg Given Once Daily for 5 or 10 Days Depending on Age and Previous Treatment History Versus Cefuroxime Axetil 15 mg/kg, Given Twice Daily for 10 Days, in Children With Acute Otitis Media
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Summary
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EudraCT number |
2004-000738-34 |
Trial protocol |
DE |
Global end of trial date |
20 Sep 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Apr 2016
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First version publication date |
11 Jun 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EFC6131
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00174811 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Other ID: HMR3647B/3001 | ||
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Sponsors
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Sponsor organisation name |
Sanofi aventis recherche & développement
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Sponsor organisation address |
1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Oct 2007
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Sep 2007
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To demonstrate the noninferiority of telithromycin with respect to cefuroxime axetil in clinical efficacy at the posttherapy/test-of-cure (TOC) visit 3 (Days 13–17) in the per protocol population (PPc population) for analysis of clinical outcome in children with acute otitis media (AOM).
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jun 2005
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 89
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Country: Number of subjects enrolled |
France: 60
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Country: Number of subjects enrolled |
Portugal: 1
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Country: Number of subjects enrolled |
Russian Federation: 3
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Country: Number of subjects enrolled |
Taiwan: 1
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Country: Number of subjects enrolled |
Argentina: 1
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Country: Number of subjects enrolled |
Peru: 35
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Country: Number of subjects enrolled |
Chile: 45
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Country: Number of subjects enrolled |
Dominican Republic: 16
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Country: Number of subjects enrolled |
Guatemala: 91
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Country: Number of subjects enrolled |
Mexico: 109
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Country: Number of subjects enrolled |
Costa Rica: 158
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Country: Number of subjects enrolled |
Panama: 30
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Worldwide total number of subjects |
639
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EEA total number of subjects |
61
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
387
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Children (2-11 years) |
252
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 43 sites in 15 countries. A total of 648 subjects were screened between 27 June 2005 and 7 June 2006. | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Of 648 screened subjects, 639 subjects were randomized. | |||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Telithromycin | |||||||||||||||||||||||||||||||||
Arm description |
Telithromycin for 10 days for high risk subjects (=<24 months of age who received antibacterials for Acute Otitis Media within the past 30 days) and 5 days for all other subjects + placebo for 5 additional days. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Telithromycin
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Investigational medicinal product code |
HMR3647B
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
25 mg/kg once daily.
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Investigational medicinal product name |
Placebo (for Cefuroxime axetil)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo matched to cefuroxime axetil 15 mg/kg twice daily.
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Arm title
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Cefuroxime axetil | |||||||||||||||||||||||||||||||||
Arm description |
Cefuroxime axetil for 10 days - Depending on local health autority guideline. | |||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Cefuroxime axetil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
15 mg/kg twice daily.
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Investigational medicinal product name |
Placebo (for Telithromycin)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo matched to telithromycin 25 mg/kg once daily.
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Baseline characteristics reporting groups
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Reporting group title |
Telithromycin
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Reporting group description |
Telithromycin for 10 days for high risk subjects (=<24 months of age who received antibacterials for Acute Otitis Media within the past 30 days) and 5 days for all other subjects + placebo for 5 additional days. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cefuroxime axetil
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Reporting group description |
Cefuroxime axetil for 10 days - Depending on local health autority guideline. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Telithromycin
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Reporting group description |
Telithromycin for 10 days for high risk subjects (=<24 months of age who received antibacterials for Acute Otitis Media within the past 30 days) and 5 days for all other subjects + placebo for 5 additional days. | ||
Reporting group title |
Cefuroxime axetil
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Reporting group description |
Cefuroxime axetil for 10 days - Depending on local health autority guideline. | ||
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End point title |
Percentage of Subjects According to Clinical Outcome in Clinically Evaluable Per-Protocol (PPc) Population [1] | ||||||||||||||||||
End point description |
Clinical cure was defined as absence of acute otitis media (AOM)-related fever, improvement in tympanic membrane and no need for surgical procedure/antibacterial administration for AOM or its complications. A subject was considered a clinical failure if a surgical procedure was performed. PPc population is defined as subjects randomized and treated and excluding for major protocol deviations, or classified as clinically indeterminate.
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End point type |
Primary
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End point timeframe |
At posttherapy (Day 13-17)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was terminated early (randomization of 639 subjects / 900 planned) the type II error was not controlled as planned and only descriptive statistics were generated. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Subjects According to Clinical Outcome in Modified Intent To Treat (mITT) Population [2] | ||||||||||||||||||
End point description |
mITT population is defined as all randomized and treated subjects . Protocol deviations were not considered and indeterminate clinical outcome were considered as failure.
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End point type |
Primary
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End point timeframe |
At posttherapy (Day 13-17)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This study was terminated early (randomization of 639 subjects / 900 planned) the type II error was not controlled as planned and only descriptive statistics were generated. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Time to Symptom Resolution in PPc Population | |||||||||
End point description |
Analysis not performed due to early termination.
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End point type |
Secondary
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End point timeframe |
Baseline up to day 10
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| Notes [3] - The number of subjects analysed were zero for this outcome measure. [4] - The number of subjects analysed were zero for this outcome measure. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Time to Symptom Resolution in mITT Population | ||||||||||||
End point description |
The time to symptom resolution was defined as mentioned in outcome measure 3. Analysis was carried out on mITT population.
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End point type |
Secondary
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End point timeframe |
Baseline up to day 10
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects with adverse events of special interest | ||||||||||||||||||
End point description |
Analysis was carried out on safety population defined as all randomized and treated subjects. One subject was randomized to receive telithromycin, but received cefuroxime and is included in the cefuroxime safety population.
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End point type |
Secondary
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End point timeframe |
Day 1 up to 14 days after the last intake of medication, or Visit 4
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (day 24 to 28) regardless of seriousness or relationship to investigational product. Analysis was performed on safety population.
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Adverse event reporting additional description |
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the ‘on treatment period’ (from the first dose of study medication and up to 7 days after the last dose of study medication or, up to 17 days after the first dose of study medication, whichever is later).
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Telithromycin
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Reporting group description |
Telithromycin for 10 days for high risk subjects (=<24 months of age who received antibacterials for Acute Otitis Media within the past 30 days) and 5 days for all other subjects + placebo for 5 additional days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cefuroxime axetil
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Reporting group description |
Cefuroxime axetil for 10 days - Depending on local health autority guideline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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15 Mar 2005 |
- Inclusion criteria were modified to include otalgia or ear tugging (interfering with normal activity) for more accurate diagnosis of AOM.
- Exclusion criteria were expanded to exclude subjects with abnormalities of the eye.
- Performance of the visual assessment at any unscheduled visits prior to Visit 3 was specified.
- The tympanometry procedure was removed from the protocol. |
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10 Mar 2006 |
- One inclusion criterion was corrected from <59 months of age to <60 months of age as the upper limit of subject age.
- Contact information for the study managers was updated.
- Paracentesis was included as an authorized procedure (in addition to tympanocentesis) to be performed by the Investigators according to their usual practice.
- Performance of Gram staining was recommended any time an middle ear fluid (MEF) sample was collected.
- Fever was defined as a minimum level of body temperature of >38° Celsius for baseline evaluation.
- Instructions were added for the visual acuity results to be reported by the site Investigator in the case report form (CRF).
- Text was modified to cover cases of assignment of more than 1 investigational product lot number per subject. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
