Clinical Trial Results:
A Phase III, Controlled, Open-Label, Randomized, Parallel Group, Multicentric, Comparative Study to Assess the Efficacy and Safety of Oral Rehydration Therapy (ORT) in Combination With Spores of Bacillus clausii (Enterogermina™) Versus ORT Alone, Administered For 5 Days in the Treatment of Acute Diarrhea in Children
Summary
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EudraCT number |
2014-004636-19 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
26 Dec 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Apr 2016
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First version publication date |
25 Jul 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_01486
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00457353 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Sanofi India Limited
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Sponsor organisation address |
Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai, Mumbai, India, 400072
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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 |
29 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 |
26 Dec 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 demonstrate the efficacy of treatment with oral rehydration therapy (ORT) in combination with Bacillus clausii probiotic strain (Enterogermina™) as compared to treatment with ORT alone, for a period of 5 days, in reducing the duration of acute diarrhea in Indian 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 |
02 Mar 2007
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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 |
India: 264
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Worldwide total number of subjects |
264
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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) |
1
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Infants and toddlers (28 days-23 months) |
185
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Children (2-11 years) |
78
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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 6 centers in India. A total of 487 subjects were screened between 02 March 2007 and 18 December 2007. | |||||||||||||||||||||
Pre-assignment
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Screening details |
Of 487 screened subjects, 264 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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ORT + Bacillus clausii | |||||||||||||||||||||
Arm description |
Oral Rehydration Therapy (ORT) along with Bacillus clausii for 5 days. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Bacillus clausii
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Investigational medicinal product code |
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Other name |
Enterogermina™
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Pharmaceutical forms |
Suspension and effervescent granules for 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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Investigational medicinal product name |
ORS
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Investigational medicinal product code |
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Other name |
ELECTRAL®
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Pharmaceutical forms |
Powder for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
ORS (based on World Health Organization formula) according to the Investigator's recommendation.
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Arm title
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Oral Rehydration Therapy | |||||||||||||||||||||
Arm description |
ORS alone for 5 days. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
ORS
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Investigational medicinal product code |
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Other name |
ELECTRAL®
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Pharmaceutical forms |
Powder for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
ORS preparations administered according to the Investigator's recommendation.
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Baseline characteristics reporting groups
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Reporting group title |
ORT + Bacillus clausii
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Reporting group description |
Oral Rehydration Therapy (ORT) along with Bacillus clausii for 5 days. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oral Rehydration Therapy
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Reporting group description |
ORS alone for 5 days. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ORT + Bacillus clausii
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Reporting group description |
Oral Rehydration Therapy (ORT) along with Bacillus clausii for 5 days. | ||
Reporting group title |
Oral Rehydration Therapy
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Reporting group description |
ORS alone for 5 days. |
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End point title |
Duration of Diarrhea | ||||||||||||
End point description |
Duration of diarrhea, as counted from the first intake of the investigational product up to the first appearance of a loose stool followed by two consecutive normal stools. Analysis was performed on safety population included all randomized and treated subjects.
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End point type |
Primary
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End point timeframe |
From D1 to end of treatment visit (Day 6)
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Statistical analysis title |
ORT + Bacillus clausii vs ORT | ||||||||||||
Statistical analysis description |
Analysis was performed by a log-rank test (Kaplan-Meier survival analysis).
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Comparison groups |
Oral Rehydration Therapy v ORT + Bacillus clausii
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Number of subjects included in analysis |
255
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.13 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
Number of Stools Per Day | ||||||||||||
End point description |
Analysis was performed on safety population. Number of subjects analysed = subjects with data available at each day.
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End point type |
Secondary
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End point timeframe |
On each day (D1 to D6)
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No statistical analyses for this end point |
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End point title |
Consistency of Stools | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Analysis was performed on safety population.
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End point type |
Secondary
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End point timeframe |
On each day (D1 to D6)
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No statistical analyses for this end point |
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End point title |
Number of Vomiting Episodes Per Day | ||||||||||||||||||||||||||||||
End point description |
Analysis was performed on safety population. Here, "n" signifies the subjects with data available at specified time point.
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End point type |
Secondary
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End point timeframe |
On each day (D1 to D6)
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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 (visit 2) 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 first dose up to 12 days after last dose).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
ORT + Bacillus clausii
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Reporting group description |
ORT along with Bacillus clausii for 5 days. | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Oral Rehydration Therapy
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Reporting group description |
ORS alone for 5 days. | ||||||||||||||||||||||||||||||||||||||||||
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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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29 Jan 2007 |
1. Method of ORS prepartion was changed.
2. As per part of the standard therapy in both the arms, Zinc supplements were given to all subjects in the dose of 20 mg/day for 14 days. |
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27 Nov 2007 |
The sample size was recalculated. The sample size with a drop out rate of 5% was determined to be 264 subjects. |
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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 |