Clinical Trial Results:
Bacillus clausii in Preventing Antibiotic-associated Diarrhea among Filipino Infants and Children: A Multi-center, Randomized, Open-label Clinical Trial of Efficacy and Safety
Summary
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EudraCT number |
2014-004629-42 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
05 Oct 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
23 May 2016
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First version publication date |
27 Jun 2015
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Other versions |
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 |
ENTER_L_01125
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00447161 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Sanofi-aventis Philippines Inc.
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Sponsor organisation address |
3rd Floor, Feliza Building, 108 V.A. Rufino Street, Legaspi Village , Makati City, Philippines, 1229
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Public contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi Aventis Recherche & Developpement, 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 |
06 Feb 2008
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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 |
05 Oct 2007
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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 |
To assess the efficacy and safety of the probiotic Bacillus clausii in preventing antibiotic-associated diarrhea among hospitalized immunocompetent Filipino infant and children.
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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 |
17 Jul 2006
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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 |
Philippines: 323
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Worldwide total number of subjects |
323
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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) |
103
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Children (2-11 years) |
210
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Adolescents (12-17 years) |
10
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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 2 sites in the Philippines. A total of 323 subjects were screened between 17 July 2006 and 15 August 2007. | |||||||||||||||
Pre-assignment
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Screening details |
All 323 subjects were randomized. | |||||||||||||||
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 |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Bacillus clausii | |||||||||||||||
Arm description |
Bacillus clausii for 7 to 21 days along with antibiotic therapy. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Bacillus clausii
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Vial containing 2 billion spores twice daily.
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Arm title
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No intervention-control | |||||||||||||||
Arm description |
Subjects received antibiotic therapy only. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Bacillus clausii
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Reporting group description |
Bacillus clausii for 7 to 21 days along with antibiotic therapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
No intervention-control
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Reporting group description |
Subjects received antibiotic therapy only. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Bacillus clausii
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Reporting group description |
Bacillus clausii for 7 to 21 days along with antibiotic therapy. | ||
Reporting group title |
No intervention-control
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Reporting group description |
Subjects received antibiotic therapy only. |
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End point title |
Number of Antibiotic-Associated Diarrhea Events | |||||||||
End point description |
Antibiotic-associated diarrhea is defined as diarrhea that occurs in association with the administration of antibiotics. Analysis was performed on all randomized and treated subjects.
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End point type |
Primary
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End point timeframe |
Day 0 to 6 weeks post treatment (maximum 9 weeks)
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Statistical analysis title |
Bacillus clausii vs No intervention-control | |||||||||
Statistical analysis description |
Relative risk was calculated from cumulative incidence ratios, and two-tailed 95% test-based confidence intervals.
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Comparison groups |
Bacillus clausii v No intervention-control
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Number of subjects included in analysis |
323
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.22 | |||||||||
Method |
Chi-squared | |||||||||
Parameter type |
Relative risk | |||||||||
Point estimate |
0.43
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.11 | |||||||||
upper limit |
1.62 |
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End point title |
Number of Antibiotic Associated Diarrhea Events Per Day | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 0 to 6 weeks post treatment (maximum 9 weeks)
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Notes [1] - Data was not analysed for this outcome measure. [2] - Data was not analysed for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Number of Gastrointestinal Related Symptoms | ||||||||||||||||||
End point description |
Gastrointestinal related symptoms included nausea, vomiting and abdominal pain. Analysis was performed on all randomized and treated subjects.
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End point type |
Secondary
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End point timeframe |
Day 0 to 6 weeks post treatment (maximum 9 weeks)
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No statistical analyses for this end point |
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End point title |
Duration of Hospital Stay | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 0 to 6 weeks post treatment (maximum 9 weeks)
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Notes [3] - Data was not analysed for this outcome measure. [4] - Data was not analysed for this outcome measure. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clostridium difficile Associated Diarrhea | |||||||||
End point description |
Analysis was performed on 10 subjects who developed diarrhea.
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End point type |
Secondary
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End point timeframe |
Day 0 to 6 weeks post treatment (maximum 9 weeks)
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No statistical analyses for this end point |
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Adverse events information [1]
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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 (Week 9) regardless of seriousness or relationship to investigational product. Analysis was performed on all randomized and treated subjects.
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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 first dose of study medication up to 14 days after the last dose of study medication).
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Assessment type |
Systematic | |||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Not applicable | |||||||||||||||
Dictionary version |
0.0
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Reporting groups
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Reporting group title |
Bacillus clausii
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Reporting group description |
Bacillus clausii for 7 to 21 days along with antibiotic therapy. | |||||||||||||||
Reporting group title |
No intervention-control
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Reporting group description |
Subjects received antibiotic therapy only. | |||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Safety was very good and no adverse events related to Bacillus clausii were reported. |
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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. | |||
Age for 1 subject was missing and in subjects enrolled per age group field of Trial Information section this subject is reported under “Children (2-11 years)” to avoid validation error. Actual age distribution is provided in baseline characteristics. |