Clinical Trial Results:
A Multicenter, Open-Label Study To Assess The Efficacy And Safety Of Potassium Clavulanate/Amoxicillin (CVA/AMPC 1:14 combination) In The Treatment Of Children With Acute Bacterial Rhinosinusitis
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Summary
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EudraCT number |
2015-004907-22 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
07 Nov 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Oct 2016
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First version publication date |
08 Oct 2016
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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 |
117150
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, +1 8664357343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, +1 8664357343,
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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? |
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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 |
21 Jan 2014
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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 |
07 Nov 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Acute Bacterial Rhinosinusitis (ABRS) is a respiratory inflammation commonly seen in clinical practice, which has with respiratory symptoms including nasal congestion, rhinorrhoea, postnasal discharge and cough and is associated with headache, cheek pain, facial pressure and other conditions. The principal bacterial pathogens in causing ABRS include Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. These three bacteria account for approximately 90% of ABRS in children <= to 5 years of age. Combination of Potassium Clavulanate (CVA) and Amoxicillin (AMPC) produces higher antibiotic activity against beta-lactamase-producing bacteria. The present study is designed to assess the clinical efficacy, bacteriological efficacy and safety of CVA/AMPC (1:14) administered in children aged from 3 months to less than 15 years with ABRS. It is an open-label study consisting of a 7-day treatment phase and a post-treatment follow-up phase for 7 to 14 days.
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Protection of trial subjects |
Not Applicable
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
30 Aug 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Japan: 27
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Worldwide total number of subjects |
27
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EEA total number of subjects |
0
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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) |
1
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Children (2-11 years) |
25
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Adolescents (12-17 years) |
1
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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 |
- | ||||||
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Pre-assignment
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Screening details |
This study assessed the efficacy and safety of potassium clavulanate/amoxicillin (CVA/AMPC 1:14 combination) in the treatment of children with acute bacterial rhinosinusitis. | ||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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CVA/AMPC (1:14) | ||||||
Arm description |
Participants received an oral dose of dry syrup potassium clavulanate (CVA)/amoxicillin hydrate (APMC) for 7 days. The daily dose of CVA/AMPC (1:14) was equal to CVA 6.4 milligrams (mg) (potency)/kilogram (kg)/day and AMPC 90 mg (potency)/kg/day in two divided doses (every 12 hours) just before lactation or meal depending on body weight at the start of treatment (Day 1). | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Potassium Clavulanate/ Amoxicillin Hydrate (CVA/AMPC)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for syrup
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received CVA/AMPC corresponding 6.4/90 mg/kg/day for 7 days. The daily dose of CVA/AMPC in concentration of 6.4/90 mg/kg/day was given in two divided doses (every 12 hours) just before lactation or meal for 7 days depending on his/her body weight at the start of treatment (Day 1)
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Baseline characteristics reporting groups
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Reporting group title |
CVA/AMPC (1:14)
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Reporting group description |
Participants received an oral dose of dry syrup potassium clavulanate (CVA)/amoxicillin hydrate (APMC) for 7 days. The daily dose of CVA/AMPC (1:14) was equal to CVA 6.4 milligrams (mg) (potency)/kilogram (kg)/day and AMPC 90 mg (potency)/kg/day in two divided doses (every 12 hours) just before lactation or meal depending on body weight at the start of treatment (Day 1). | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
CVA/AMPC (1:14)
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Reporting group description |
Participants received an oral dose of dry syrup potassium clavulanate (CVA)/amoxicillin hydrate (APMC) for 7 days. The daily dose of CVA/AMPC (1:14) was equal to CVA 6.4 milligrams (mg) (potency)/kilogram (kg)/day and AMPC 90 mg (potency)/kg/day in two divided doses (every 12 hours) just before lactation or meal depending on body weight at the start of treatment (Day 1). | ||
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End point title |
Number of participants with a clinical outcome of "cure" at Test of Cure (TOC: Day 15) [1] | ||||||||||||||
End point description |
Clinical assessment of acute bacterial rhinosinusitis was performed at TOC (Day 15) on the basis of: "Cure" is defined as sufficient resolution or improvement of the signs and symptoms (SS) such that no additional antibiotic (Ab) therapy is needed. Failure is defined as no change or deterioration of the SS or as additional Ab therapy being needed. The outcome was unable to be determined if no information was available regarding the SS or, despite improvement of the SS, the use of a non-study Ab was administered, indicating that there was a protocol deviation (Pd). Per Protocol Population: all participants (Par) randomized to treatment (Tr) who received the study drug for at least the first 3 days of study Tr and had evaluable data on both Day 8 and Day 15 with Tr compliance between 80% and 100% and no major pd. The estimated parameter (88.5) with 95% Confidence interval of 69.85- 97.55 represents the rate of cure (number of Par with an outcome of "Cure"/number of Par analyzed) * 100.
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End point type |
Primary
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End point timeframe |
Day 15
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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: There are no statistical data to report. |
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| Notes [2] - Per protocol (PP) Population |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of participants with a clinical outcome of "cure" at the End of Treatment (EOT: Day 8) | ||||||||||||||
End point description |
Clinical assessment of acute bacterial rhinosinusitis was performed by the investigator (or subinvestigator) at the EOT (Day 8) on the basis of the following criteria: "Cure" is defined as sufficient resolution or improvement of the signs and symptoms such that no additional antibiotic therapy is needed. Failure is defined as no change or deterioration of the signs and symptoms or as additional antibiotic therapy being needed. The outcome was unable to be determined if no information was available regarding the signs and symptoms or, despite improvement of the signs and symptoms, the use of a non-study antibiotic was administered, indicating that there was a protocol deviation.
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End point type |
Secondary
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End point timeframe |
Day 8
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| Notes [3] - PP Population |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of participants with a clinical outcome of "cure" at both the End of Treatment and Test of Cure (EOT and TOC: Day 8 and Day 15) | ||||||||||||||
End point description |
Clinical assessment of acute bacterial rhinosinusitis was performed by the investigator (or subinvestigator) at the EOT (Day 8) and TOC (Day 15) on the basis of the following criteria: "Cure" is defined as sufficient resolution or improvement of the signs and symptoms such that no additional antibiotic therapy is needed. Failure is defined as no change or deterioration of the signs and symptoms or as additional antibiotic therapy being needed. The outcome was unable to be determined if no information was available regarding the signs and symptoms or, despite improvement of the signs and symptoms, the use of a non-study antibiotic was administered, indicating that there was a protocol deviation. In order to be categorized as "cure," participants had to meet the criteria for "cure" at both Day 8 and Day 15.
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End point type |
Secondary
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End point timeframe |
Day 8 and Day 15
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| Notes [4] - PP Population |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of participants with the indicated severity of symptoms and nasal cavity findings at Day 4, Day 8, and Day 15 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The investigator (or sub-investigator) categorized the severity of symptoms such as rhinorrhoea and bad mood/productive cough as none, mild/small amount (M/SA), or moderate or severe (M or S). For the nasal cavity finding of nasal/postnasal discharge (N/PD) the categozation was serous [containing serum]), mucopurulent (MU/SA [containing both mucus and pus]), and moderate or larger amount (M/LA). In cases in which both sides of the nasal cavity were affected and there was no difference in severity between the sides, the right-side results were recorded. If there was a difference in severity, the more severe-side results were recorded.
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End point type |
Secondary
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End point timeframe |
Baseline (BL), Day 4, Day 8, and Day 15
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| Notes [5] - PP Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants (par.) with the specified bacteriological (bact.) outcome per pathogen (path.) at the End of Treatment (EOT) at Day 8 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The investigator used the sample collected at the start of study treatment (trt) to isolate and identify the pathogenic bacteria. The sample collected at the EOT was used to evaluate the bact. response to the investigational product of each path. If the same pathogen was not detected at the EOT, this pathogen was classified as "eradication" (E). If the same pathogen was detected at the EOT, this pathogen was classified as "persistence" (P). Bacteriology PP Population: all participants in the PP Population, excluding the participants who were classified as “Unable to determine” for the bacteriological outcome and who had no identified pathogen at Day 1.
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End point type |
Secondary
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End point timeframe |
Day 8
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| Notes [6] - Bacteriology PP Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants (par.) with the specified bacteriological (bact.) outcome per participant at EOT (Day 8) | ||||||||||||
End point description |
The investigator used the sample collected at the start of study treatment (trt) to isolate and identify the pathogenic bacteria. The sample collected at the EOT was used to evaluate the bact. response to the investigational product of each par. using the following classification: Bact. eradication (erad.), presumed bact. erad. and colonization were categorized as erad. Bact. persistence (pers.), presumed bact. pers. and superinfection were categorized as pers. Bact. erad. elimination of the pathogen (path.) after trt; presumed bact. erad.-resolution of signs/symptoms (s/s) after trt; colonization-resolution of s/s but initial path. still recovered from sample; bact. pers.-no improvement in s/s and initial path. was recovered from sample; presumed bact. pers.-no improvement in s/s and isolation of initial path. was impossible/not performed; superinfection-initial path. was eradicated but a new path. was recovered; unable to determine-bact. test could not be performed.
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End point type |
Secondary
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End point timeframe |
Day 8
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| Notes [7] - Bacteriology PP Population |
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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 |
On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to Study Day 22).
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Adverse event reporting additional description |
SAEs and non-serious AEs were reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
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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 |
16.1
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Reporting groups
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Reporting group title |
CVA/AMPC (1:14)
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Reporting group description |
Participants received an oral dose of dry syrup potassium clavulanate (CVA)/amoxicillin hydrate (APMC) for 7 days. The daily dose of CVA/AMPC (1:14) was equal to CVA 6.4 milligrams (mg) (potency)/kilogram (kg)/day and AMPC 90 mg (potency)/kg/day in two divided doses (every 12 hours) just before lactation or meal depending on body weight at the start of treatment (Day 1). | ||||||||||||||||||||||||||||
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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? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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 | |||
