Clinical Trial Results:
Multicentre, prospective, double-blind, two-armed, placebo-controlled phase III study to evaluate the efficacy and safety of the treatment of diarrhoea with Lactobacillus rhamnosus GG (InfectoDiarrstop LGG Mono Beutel) in infants and toddlers
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Summary
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EudraCT number |
2012-002291-13 |
Trial protocol |
DE PL |
Global end of trial date |
25 Nov 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Dec 2022
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First version publication date |
15 Dec 2022
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Other versions |
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Summary report(s) |
EudraCT-Report-DIALAGG |
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 |
DIALAGG
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Infectopharm Arzneimittel GmbH
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Sponsor organisation address |
Von-Humboldt-Str. 1, Heppenheim, Germany, 64646
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Public contact |
Project Manager, Infectopharm Arzneimittel GmbH, +49 6252 958104, studien@infectopharm.com
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Scientific contact |
Project Manager, Infectopharm Arzneimittel GmbH, +49 6252 958104, bertil.wachall@infectopharm.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 May 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 Nov 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
25 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 |
Duration of diarrhoea (time until therapeutic success, i.e. end of diarrhoea, defined as ≤ 3 watery and/or loose stools per day during the past 2 days without recurrence of the diarrhoea until the end of the treatment)
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Protection of trial subjects |
Patients in both the verum and the placebo group received the recommended first-line treatment of an oral rehydration solution. Furthermore, the study could be terminated should an adverse event occur posing an inadequately high risk to the patient or if the investigator considered the patient’s participation no longer justifiable. In the case of no clinical improvement of the diarrhoea at the control visit on day 2, the patient’s participation could be terminated immediately. Inadequate treatment of specific severe cases of diarrhoea, e.g. with bloody stools, having diarrhoea for more than three days, or with moderate to severe dehydration, was also precluded by the respective exclusion criteria.
According to the “Ethical considerations for clinical studies performed in children” by the European Commission [Directive 2001/20/EC, 2006] the present clinical study should be classified as a “minimal risk” study, because the probability of harm or discomfort in the study was no greater than those ordinarily encountered in daily life or during the performance of routine examinations. Furthermore, the overall coordinating investigator permanently monitored the harm and discomfort of the paediatric patients as well as the threshold of minimal risk.
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Background therapy |
Oral rehydration solution (ORS) according to ESPGHAN recommendations | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Jan 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 |
Poland: 52
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Country: Number of subjects enrolled |
Germany: 98
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Worldwide total number of subjects |
150
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EEA total number of subjects |
150
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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) |
150
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Children (2-11 years) |
0
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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 |
Infants and toddlers, aged 28 days to 24 months, with clinically diagnosed diarrhoea (> 3 watery and/or loose stools during the past 24 hours) from establishes pediatricians were enrolled. | |||||||||
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Pre-assignment
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Screening details |
No specfic pre-assignment was conducted. | |||||||||
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Period 1
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Period 1 title |
Overall trial (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, Monitor, Data analyst, Carer, Assessor | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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InfectoDiarrstop LGG Mono | |||||||||
Arm description |
Active pharmaceutical ingredient: Lactobacillus rhamnosus GG (LGG) Concentration: ≥ 5 x 10*9 (CFU) (lyophilised) Pharmaceutical form: sachets with powder to prepare a suspension (in water, directly before use) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
InfectoDiarrstop LGG Mono
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Investigational medicinal product code |
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Other name |
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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 |
1 sachet (≥ 5 x 10*9 (CFU) to be suspended in as little water as possible) for oral intake twice a day (every morning and evening) for a total of 10 days
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Arm title
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Placebo | |||||||||
Arm description |
Placebo (active pharmaceutical ingredient replaced by microcrystalline cellulose) | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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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 |
1 sachet (to be suspended in as little water as possible) for oral intake twice a day (every morning and evening) for a total of 10 days
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
FAS
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who were randomised and have taken at least one dose of trial medication
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End points reporting groups
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Reporting group title |
InfectoDiarrstop LGG Mono
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Reporting group description |
Active pharmaceutical ingredient: Lactobacillus rhamnosus GG (LGG) Concentration: ≥ 5 x 10*9 (CFU) (lyophilised) Pharmaceutical form: sachets with powder to prepare a suspension (in water, directly before use) | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo (active pharmaceutical ingredient replaced by microcrystalline cellulose) | ||
Subject analysis set title |
FAS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients who were randomised and have taken at least one dose of trial medication
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End point title |
duration of diarrhoea | ||||||||||||||||
End point description |
≤ 3 watery and/or loose stools per day during the past 2 days without recurrence of the diarrhoea until the end of the treatment
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End point type |
Primary
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End point timeframe |
End of diarrhoea
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Statistical analysis title |
Primary efficacy analysis | ||||||||||||||||
Statistical analysis description |
Duration of diarrhoea, one-sided t-test, significance level of 2.5%
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Comparison groups |
InfectoDiarrstop LGG Mono v Placebo
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Number of subjects included in analysis |
150
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 888888 [1] | ||||||||||||||||
Method |
t-test, 1-sided | ||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||
Point estimate |
888888
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
1-sided
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lower limit |
888888 | ||||||||||||||||
upper limit |
- | ||||||||||||||||
| Notes [1] - Due to relevant problems of data quality and potential misconduct identified after the study was completed no valid data set could be obtained. Therefore, a robust evaluation was not possible and no results are available. |
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Adverse events information
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Timeframe for reporting adverse events |
From enrolement to last visit
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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 |
16.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo | |||||||||||||||||||||||||||||||||||||||
Reporting group title |
InfectoDiarrstop LGG Mono
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Reporting group description |
Verum | |||||||||||||||||||||||||||||||||||||||
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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 | |||
