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| ID | Type | Description | Link |
|---|---|---|---|
| U01AI118506 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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The objective of this trial is to determine whether certain subgroups of children with acute sinusitis exist in whom antibiotic therapy can be appropriately withheld.
The current clinical practice guideline from the American Academy of Pediatrics for the Diagnosis and Management of Acute Bacterial Sinusitis recommends that the diagnosis of acute sinusitis is made when symptoms of an upper respiratory infection (URI) persist beyond 10 days without showing signs of improvement (persistent presentation), when symptoms appear to worsen (on the 6th to 10th day) after a period of improvement (worsening presentation), or when both high fever and purulent nasal discharge are present concurrently for at least 3 consecutive days (severe presentation). In studies to date, children with persistent and worsening presentations comprise >95% of cases. The investigators preliminary data and the available literature suggest that only a subset of children being diagnosed with acute sinusitis on the basis of current criteria are likely to have bacterial disease. This is not entirely surprising because current criteria rely solely on the duration and the quality of respiratory tract symptoms (which are both common and non-specific). Accordingly, it seems likely that many children currently being diagnosed as having acute sinusitis actually have an uncomplicated upper respiratory infection. This is important because acute sinusitis is one of the most common diagnoses for which antimicrobials are prescribed for children in the United States, accounting for 7.9 million prescriptions annually. A critical need thus exists to establish which subgroups of children currently being diagnosed with acute sinusitis actually benefit from antimicrobial therapy.
The objective of this trial is to determine whether certain subgroups of children with acute sinusitis exist in whom antibiotic therapy can be appropriately withheld. This objective will be achieved by conducting a large, randomized, double-blind, placebo-controlled clinical trial in children 2 to 12 years of age with persistent or worsening presentations of acute sinusitis. Based on the investigators preliminary data, the investigators hypothesize that only certain subgroups of children currently being treated for acute sinusitis actually benefit from antimicrobial therapy. By identifying, in a large placebo-controlled trial, subgroups of children who respectively do and do not benefit from antimicrobial therapy, the investigators will be better able to determine which children should be classified as having acute bacterial sinusitis. Accordingly, the results of this trial may impact not only the treatment guidelines for acute sinusitis but also the diagnostic criteria, and will help ensure that, to the extent possible, antibiotic use is limited to appropriate patients. This, in turn, will maximize the likelihood of achieving optimal outcomes and minimize the risk of promoting antibiotic resistance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Active Comparator | Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days) |
|
| Treatment B | Placebo Comparator | Placebo made to match the study antibiotic will be taken bid orally for 10 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amoxicillin-clavulanate | Drug | Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days) |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment | The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough & trouble sleeping - as none, almost none, a little, some, a lot & an extreme amount with respective scores of 0, 1, 2, 3, 4 & 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) & electronically on diaries evenings Days 2-11. Pathogens cultured were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. | Days 2 to 11 |
| The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment | The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough & trouble sleeping - as none, almost none, a little, some, a lot & an extreme amount with respective scores of 0, 1, 2, 3, 4 & 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) & electronically on diaries evenings Days 2-11. Nasal discharge, either yellow or green, was considered colored. | Days 2 to 11 |
| Measure | Description | Time Frame |
|---|---|---|
| The Distribution of Children Experiencing Treatment Failure (TF) | The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough & trouble sleeping - as none, almost none, a little, some, a lot & an extreme amount with respective scores of 0, 1, 2, 3, 4 & 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment), electronically evenings Days 2-11 & at the follow-up visit. If, compared to the Day 1 score, there was >20% increase at any time, decrease <2 on Day 3, <20% decrease on Day 4, <20% decrease on 2 consecutive occasions Days 5-11 or <50% decrease at follow-up, then criterion for treatment failure (TF) was met. Multiple imputation was used when data was insufficient to assess TF. |
| Measure | Description | Time Frame |
|---|---|---|
| The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit | The nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (SPN) and ß-lactamase-positive Haemophilus influenzae (NTHi). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of <=0.06 μg/mL; intermediate as an MIC of greater than 0.06 to less than 2 μg/mL; and resistant as an MIC of >=2 μg/mL. A nasopharyngeal specimen for bacterial culture was obtained at the time of the follow-up visit, occurring between study days 11 and 23. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nader Shaikh, MPH, MD | University of Pittsburgh | Principal Investigator |
| Ellen R Wald, MD | University of Wisconsin, American Family Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kentucky Pediatric/Adult Research | Bardstown | Kentucky | 40004 | United States | ||
| Cyn3rgy Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37490085 | Derived | Shaikh N, Hoberman A, Shope TR, Jeong JH, Kurs-Lasky M, Martin JM, Bhatnagar S, Muniz GB, Block SL, Andrasko M, Lee MC, Rajakumar K, Wald ER. Identifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial. JAMA. 2023 Jul 25;330(4):349-358. doi: 10.1001/jama.2023.10854. |
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Children determined to be eligible for the study and whose parents agreed to participation were randomized to one of two treatments arms. At each site of enrollment, within stratum defined by the presence/absence of colored (yellow or green) nasal discharge, children were randomized 1:1 in blocks of four to receive either twice daily amoxicillin-clavulanate or matching placebo. The analyses of study data were based on the randomized treatment assignment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Amoxicillin-clavulanate | Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days) |
| FG001 | Placebo | Placebo made to match the study antibiotic (will be taken bid orally for 10 days) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
515 children underwent randomization; 257 were randomized to the amoxicillin-clavulanate group and 258 to the placebo group. 3 and 2, respectively, were found ineligible after randomization. The remaining 254 and 256 participants, respectively, were the basis for analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Amoxicillin-clavulanate | Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days) |
| BG001 | Placebo | Placebo made to match the study antibiotic (will be taken bid orally for 10 days) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Pathogens in the Nasopharynx at Enrollment | The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough & trouble sleeping - as none, almost none, a little, some, a lot & an extreme amount with respective scores of 0, 1, 2, 3, 4 & 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) & electronically on diaries evenings Days 2-11. Pathogens cultured were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. | The analysis was intention-to-treat (ITT). The overall number of participants analyzed is equal to the number of children randomized & eligible who had results of a nasopharyngeal culture at enrollment and whose parent completed the PRSS at least once Days 2 to 11. For any given day, the total number analyzed plus the total number without diary data available on that day is equal to the overall number of participants analyzed for the respective Arm/Group. | Posted | Mean | Standard Deviation | Score on a scale | Days 2 to 11 |
The monitoring of adverse events (AEs) began on Day 1 (enrollment) and continued through Day 23 (the follow-up visit). All recorded AEs were followed to adequate resolution.
Parents recorded in daily diaries, Days 1-11, information regarding the occurrence of diarrhea. Additionally, parents were asked at the follow-up visit if their child had diarrhea while on study product.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Amoxicillin-clavulanate | Amoxicillin-clavulanate (90/6.4 mg/kg/d in 2 divided dosed for 10 days) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment | Diarrhea was the occurrence of 3 or more watery stools on one day or 2 watery stools on each of 2 consecutive days. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nader Shaikh | University of Pittsburgh | 412-692-8111 | nader.shaikh@chp.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 2, 2021 | Mar 28, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012852 | Sinusitis |
| D012141 | Respiratory Tract Infections |
| ID | Term |
|---|---|
| D007239 | Infections |
| D010254 | Paranasal Sinus Diseases |
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D019980 | Amoxicillin-Potassium Clavulanate Combination |
| ID | Term |
|---|---|
| D019818 | Clavulanic Acid |
| D002969 | Clavulanic Acids |
| D047090 | beta-Lactams |
| D007769 | Lactams |
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| Placebo | Drug | placebo made to match the study antibiotic given twice a day orally for 10 days |
|
| Day of enrollment to the day of the follow-up visit. The mean length of actual follow-up was 13.4 days. For each child with incomplete follow-up, multiple imputation was used and PRSS scores for the remaining days were imputed. |
| The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up | AOM is an infection of the middle ear marked by acute symptoms and a bulging tympanic membrane. Its diagnosis coincided with receipt of a systemic antibiotic. Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin & Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded. | Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8. |
| The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up | Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin & Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded. The antibiotic received is exclusive of the study product assigned at enrollment. | Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8. |
| The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported | The monitoring of adverse events (AEs), i.e. diarrhea or generalized rash, began on Day 1 (enrollment) and continued through Day 23 (the follow-up visit). Diarrhea was the occurrence of 3 or more watery stools on one day or 2 watery stools on each of 2 consecutive days. Parents recorded in daily diaries, Days 1-11, information regarding the occurrence of diarrhea. Additionally, parents were asked at the follow-up visit if their child had diarrhea while on study product. | Day 1 through Day 23. |
| The Distribution of Children Compliant With Study Medication | Compliance, expressed as a percentage, is the total number of doses taken divided by the total number of expected doses. The child is considered compliant if he/she has received at least 70% of the study medication. The parent completed diaries evenings Days 2-11. The diaries included yes/no questions - (1) did your child take the study medication last night and (2) did your child take the study medication this morning? The total number of doses taken was calculated based on the responses to question (1), and accounted for the dose dispensed at enrollment when enrollment was 1pm or earlier on Day 1. The total of expected doses was determined from the responses to questions (1) and (2), and accounted for scenarios in which the child was taken off the study medication by the clinician. In some cases, due to incomplete diaries the information was insufficient to declare a child either compliant or not compliant. | Days 1 to 11, where Day 1 is day of enrollment |
| The follow-up visit. The mean number of days from enrollment to the follow-up visit was 13.4. |
| Gresham |
| Oregon |
| 97030 |
| United States |
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| UPMC Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
| WVU Medicine Pediatric and Adolescent Group Practice | Morgantown | West Virginia | 26501 | United States |
| American Family Children's Hospital | Madison | Wisconsin | 53792 | United States |
| Parent completed 0 diaries by Day 4 and >=1 diary Days 5-11 |
|
| Parent completed >=1 diary by Day 4, but <2 diaries Days 2-4 or <3 diaries Days 5-11 |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Ethnicity was reported by the parent. | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race was reported by the parent. | Count of Participants | Participants |
|
| Study Site | Participating primary care offices were affiliated with the: (1) Children's Hospital of Pittsburgh, Pittsburgh, PA (2) Children's Hospital of Philadelphia, Philadelphia, PA; (3) Kentucky Pediatric and Adult Research, Bardstown, KY (4) University of Wisconsin, Madison, WI, (5) West Virginia University Children's, Morgantown, WV, and (6) Cyn3rgy Research, Gresham, OR. | Count of Participants | Participants |
|
| History of Asthma | Count of Participants | Participants |
|
| History of Allergic Rhinitis | Count of Participants | Participants |
|
| Fever | Fever at any time during the illness | Count of Participants | Participants |
|
| Exposure to Other Children | Exposure to other children was defined as exposure to at least 3 children for at least 10 hours per week. | Count of Participants | Participants |
|
| Type of Presentation | Persistent was defined as the presence of symptoms for 11 days or longer without improvement. Worsening was defined as a period of improvement followed by worsening symptoms on days 6-10 | Count of Participants | Participants |
|
| Pediatric Rhinosinusitis Symptom Scale (PRSS) Score | The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough & trouble sleeping - as none, almost none, a little, some, a lot & an extreme amount with respective scores of 0, 1, 2, 3, 4 & 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. | Count of Participants | Participants |
|
| Pathogens Cultured from Nasopharynx | Pathogens cultured were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. | Count of Participants | Participants |
|
| Colored Nasal Discharge | Nasal discharge, either yellow or green, was considered colored. | Count of Participants | Participants |
|
|
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|
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| Primary | The Mean Pediatric Rhinosinusitis Symptom Scale (PRSS) Score Over the First 10 Days of Follow-up According to the Presence of Colored Nasal Discharge at Enrollment | The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough & trouble sleeping - as none, almost none, a little, some, a lot & an extreme amount with respective scores of 0, 1, 2, 3, 4 & 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment) & electronically on diaries evenings Days 2-11. Nasal discharge, either yellow or green, was considered colored. | The analysis was ITT. The overall number of participants analyzed is equal to the number of children randomized & eligible whose parent completed the PRSS at least once Days 2 to 11. For any given day, the total number analyzed plus the total number without diary data available on that day is equal to the overall number of participants analyzed for the respective Arm/Group. | Posted | Mean | Standard Deviation | Score on a scale | Days 2 to 11 |
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|
|
| Secondary | The Distribution of Children Experiencing Treatment Failure (TF) | The Pediatric Rhinosinusitis Symptom Scale (PRSS) is a 8 item scale assessing symptoms of sinusitis. Parents are asked how their child has been doing over the last 24 hours by rating each of 8 symptoms - stuffy nose, runny nose, daytime cough, tiredness, irritability, trouble breathing through the nose, nighttime cough & trouble sleeping - as none, almost none, a little, some, a lot & an extreme amount with respective scores of 0, 1, 2, 3, 4 & 5. The 8 ratings were summed to obtain a PRSS score. Scores ranged from 0-40. Higher scores indicate greater severity. The parent completed the scale on Day 1 (enrollment), electronically evenings Days 2-11 & at the follow-up visit. If, compared to the Day 1 score, there was >20% increase at any time, decrease <2 on Day 3, <20% decrease on Day 4, <20% decrease on 2 consecutive occasions Days 5-11 or <50% decrease at follow-up, then criterion for treatment failure (TF) was met. Multiple imputation was used when data was insufficient to assess TF. | The analysis was ITT. The number of participants is equal to the number of children randomized & eligible. | Posted | Count of Participants | Participants | Day of enrollment to the day of the follow-up visit. The mean length of actual follow-up was 13.4 days. For each child with incomplete follow-up, multiple imputation was used and PRSS scores for the remaining days were imputed. |
|
|
|
|
| Secondary | The Distribution of Children Developing Acute Otitis Media (AOM) Over the First 10 Days of Follow-up | AOM is an infection of the middle ear marked by acute symptoms and a bulging tympanic membrane. Its diagnosis coincided with receipt of a systemic antibiotic. Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin & Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded. | The analysis was ITT. The number of participants is equal to the number of children randomized & eligible with follow-up post-enrollment. | Posted | Count of Participants | Participants | Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8. |
|
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|
|
| Secondary | The Distribution of Children Receiving a Systemic Antibiotic Over the First 10 Days of Follow-up | Systemic antibiotics include Amoxicillin, Amoxicillin-clavulanate, Azithromycin, Bacillin L-A, Cefdinir, Clindamycin, Doxycycline, Levofloxacin, Ofloxacin & Sulfamethoxazole-Trimethoprim. Start and stop dates were recorded. The antibiotic received is exclusive of the study product assigned at enrollment. | The analysis was ITT. The number of participants is equal to the number of children randomized & eligible with follow-up post-enrollment. | Posted | Count of Participants | Participants | Days 2 to 11, where Day 1 is day of enrollment. The mean number of days of follow-up in this interval was 9.8. |
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| Secondary | The Distribution of Children for Whom Diarrhea or Generalized Rash Was Reported | The monitoring of adverse events (AEs), i.e. diarrhea or generalized rash, began on Day 1 (enrollment) and continued through Day 23 (the follow-up visit). Diarrhea was the occurrence of 3 or more watery stools on one day or 2 watery stools on each of 2 consecutive days. Parents recorded in daily diaries, Days 1-11, information regarding the occurrence of diarrhea. Additionally, parents were asked at the follow-up visit if their child had diarrhea while on study product. | The analysis was ITT. The number of participants is equal to the number of children randomized & eligible | Posted | Count of Participants | Participants | Day 1 through Day 23. |
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| Secondary | The Distribution of Children Compliant With Study Medication | Compliance, expressed as a percentage, is the total number of doses taken divided by the total number of expected doses. The child is considered compliant if he/she has received at least 70% of the study medication. The parent completed diaries evenings Days 2-11. The diaries included yes/no questions - (1) did your child take the study medication last night and (2) did your child take the study medication this morning? The total number of doses taken was calculated based on the responses to question (1), and accounted for the dose dispensed at enrollment when enrollment was 1pm or earlier on Day 1. The total of expected doses was determined from the responses to questions (1) and (2), and accounted for scenarios in which the child was taken off the study medication by the clinician. In some cases, due to incomplete diaries the information was insufficient to declare a child either compliant or not compliant. | The analysis was ITT. The number of participants is equal to the number of children randomized & eligible with information sufficient to determine compliance. | Posted | Count of Participants | Participants | Days 1 to 11, where Day 1 is day of enrollment |
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| Other Pre-specified | The Distribution of Children With a Nonsusceptible Pathogen at the Follow-up Visit | The nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (SPN) and ß-lactamase-positive Haemophilus influenzae (NTHi). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of <=0.06 μg/mL; intermediate as an MIC of greater than 0.06 to less than 2 μg/mL; and resistant as an MIC of >=2 μg/mL. A nasopharyngeal specimen for bacterial culture was obtained at the time of the follow-up visit, occurring between study days 11 and 23. | The analysis was ITT. The number of participants is equal to the number of children randomized & eligible with a nasopharyngeal specimen obtained at the time of the follow-up visit | Posted | Count of Participants | Participants | The follow-up visit. The mean number of days from enrollment to the follow-up visit was 13.4. |
|
|
|
|
| 0 |
| 254 |
| 0 |
| 254 |
| 29 |
| 254 |
| EG001 | Placebo | Placebo made to match the study antibiotic (will be taken bid orally for 10 days) | 0 | 256 | 0 | 256 | 12 | 256 |
|
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| D010038 |
| Otorhinolaryngologic Diseases |
| D000577 |
| Amides |
| D009930 | Organic Chemicals |
| D000658 | Amoxicillin |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| Presence of colored nasal discharge at enrollment - Day 3 |
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| Presence of colored nasal discharge at enrollment - Day 4 |
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| Presence of colored nasal discharge at enrollment - Day 5 |
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| Presence of colored nasal discharge at enrollment - Day 6 |
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| Presence of colored nasal discharge at enrollment - Day 7 |
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| Presence of colored nasal discharge at enrollment - Day 8 |
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| Presence of colored nasal discharge at enrollment - Day 9 |
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| Presence of colored nasal discharge at enrollment - Day 10 |
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| Presence of colored nasal discharge at enrollment - Day 11 |
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| Absence of colored nasal discharge at enrollment - Day 2 |
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| Absence of colored nasal discharge at enrollment - Day 3 |
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| Absence of colored nasal discharge at enrollment - Day 4 |
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| Absence of colored nasal discharge at enrollment - Day 5 |
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| Absence of colored nasal discharge at enrollment - Day 6 |
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| Absence of colored nasal discharge at enrollment - Day 7 |
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| Absence of colored nasal discharge at enrollment - Day 8 |
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| Absence of colored nasal discharge at enrollment - Day 9 |
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| Absence of colored nasal discharge at enrollment - Day 10 |
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| Absence of colored nasal discharge at enrollment - Day 11 |
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| Null hypothesis: There is no difference between the treatment groups in the subgroup of children defined by the presence of colored nasal discharge at enrollment. | Difference of least-squares means | -1.62 | 2-Sided | 95 | -2.09 | -1.16 | The Amoxicillin-clavulanate group represents the first number in the subtraction and the Placebo group represents the second. The estimates are adjusted for PRSS score at enrollment, diary day and study site. | Superiority |
| Null hypothesis: There is no difference between the treatment groups in the subgroup of children defined by the absence of colored nasal discharge at enrollment. | Difference of least-squares means | -1.70 | 2-Sided | 95 | -2.38 | -1.03 | The Amoxicillin-clavulanate group represents the first number in the subtraction and the Placebo group represents the second. The estimates are adjusted for PRSS score at enrollment, diary day and study site. | Superiority |