Clinical Trial Results:
A randomized, double-blind, placebo-controlled study of the usefulness of the probiotic 'Lactobacillus reuteri' in the therapy of quadruple eradication of Helicobacter pylori infection in usual clinical practice
Summary
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EudraCT number |
2017-000342-22 |
Trial protocol |
ES |
Global end of trial date |
01 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Apr 2020
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First version publication date |
17 Apr 2020
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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 |
VALACT-2017-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Dr. Luis Fernández-Dr. Jesus Barrio
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Sponsor organisation address |
Hosp Clín Univ Valladolid-Hosp Univ Río Hortega Valladolid, Valladolid, Spain,
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Public contact |
Dr. Jesus Barrio
Hosp Univ Río Hortega Valladolid, Dr. Luis Fernández
Hosp Clín Univ Valladolid
, +34 9999999, jbarrioa95@gmail.com
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Scientific contact |
Dr. Jesus Barrio
Hosp Univ Río Hortega Valladolid, Dr. Luis Fernández
Hosp Clín Univ Valladolid
, +34 9999999, jbarrioa95@gmail.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Sep 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Aug 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Aug 2018
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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 know if supplementation with Gastrus (food supplement) vs Placebo is able of lowering the gastrointestinal adverse effects of quadruple eradication therapy determined by the GSRS gastrointestinal symptom scale in routine clinical practice.
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Protection of trial subjects |
The study was in compliance with ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
Eradicator treatment with quadruple therapy (at the discretion of the responsible physician): - Quadruple with bismuth: Pylera (three in one tablets: bismuth, tetracyclines and metronidazole): 3 tablets every 6 hours and omeprazole of 20 mg 1 tablet every 12 hours for 10 consecutive days. - Quadruple without bismuth: Esomeprazole 40 mg 1 tablet every 12 hours, Amoxicillin 1 g every 12 hours, Clarithromycin 500 mg every 12 hours, Metronidazole 500 mg every 12 hours, all for 14 consecutive days. | ||
Evidence for comparator |
Placebo-controlled study to confirm the usefulness of the probiotic 'Lactobacillus reuteri' | ||
Actual start date of recruitment |
01 Jan 2017
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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 |
Spain: 86
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Worldwide total number of subjects |
86
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EEA total number of subjects |
86
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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) |
0
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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) |
79
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Two centers involved and 86 subjects participated in the study. Data collection began in January 2017 and ended in August 2018. Seven subjects did not meet the age inclusion criteria and two subjects did not meet the exclusion criterion 3 “Patient treated with NSAIDs”, so their data is not analysed. 77 subjects were declared valid for analysis. | |||||||||
Pre-assignment
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Screening details |
Aged 18-65 years; Positive diagnosis of H pylori infection. | |||||||||
Period 1
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Period 1 title |
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 | |||||||||
Blinding implementation details |
All study treatments were supplied in a way in that they are indistinguishable from each other, in order to maintain the masking of the clinical trial.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Gastrus | |||||||||
Arm description |
Gastrus (a dietary supplement containing Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 6475). The daily Gastrus dose was one tablet per day (2x108 UFC). It was administered from the first day of the eradicator treatment until completing 30 days of treatment. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Gastrus
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Investigational medicinal product code |
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Other name |
Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 6475
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily Gastrus dose was one tablet per day (2x108 UFC). It was administered from the first day of the eradicator treatment until completing 30 days of treatment.
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Arm title
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Placebo | |||||||||
Arm description |
The daily placebo dose was one tablet per day. It was administered from the first day of the eradicator treatment until completing 30 days of treatment. | |||||||||
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 |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily placebo dose was one tablet per day. It was administered from the first day of the eradicator treatment until completing 30 days of treatment.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Seven subjects did not meet the age inclusion criteria, not exceeding 65 years, so their data is not analysed. In a subject, the exclusion criterion 3 “The patient is treated with NSAIDs” was not specified, so that subject is not considered valid for analysis either. Another patient was treated with NSAIDs, which is also excluded from the analysis. 77 subjects were declared valid for analysis. |
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Baseline characteristics reporting groups
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Reporting group title |
Gastrus
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Reporting group description |
Gastrus (a dietary supplement containing Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 6475). The daily Gastrus dose was one tablet per day (2x108 UFC). It was administered from the first day of the eradicator treatment until completing 30 days of treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
The daily placebo dose was one tablet per day. It was administered from the first day of the eradicator treatment until completing 30 days of treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Gastrus
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Reporting group description |
Gastrus (a dietary supplement containing Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 6475). The daily Gastrus dose was one tablet per day (2x108 UFC). It was administered from the first day of the eradicator treatment until completing 30 days of treatment. | ||
Reporting group title |
Placebo
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Reporting group description |
The daily placebo dose was one tablet per day. It was administered from the first day of the eradicator treatment until completing 30 days of treatment. |
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End point title |
Change GSRS at day 15 from baseline: Total score | |||||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Primary
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End point timeframe |
At day 15 of treatment
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Statistical analysis title |
Differences between groups | |||||||||||||||
Comparison groups |
Placebo v Gastrus
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Number of subjects included in analysis |
73
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.532 | |||||||||||||||
Method |
ANOVA | |||||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 15 from baseline: Pain syndrome | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At day 15
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.846 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 15 from baseline: Dyspeptic syndrome | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
At day 15
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.219 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 15 from baseline: Indigestion syndrome | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
At day 15
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Placebo v Gastrus
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.474 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 15 from baseline: Colon dysfunction syndrome | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
At dat 15
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
72
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.41 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 31 from baseline: Total score | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
Overall period
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.583 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 31 from baseline: Pain syndrome | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
Overall period
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.963 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 31 from baseline: Dyspeptic syndrome | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
Overall period
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.389 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 31 from baseline: Indigestion syndrome | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
Overall period
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.441 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Change GSRS at day 31 from baseline: Colon dysfunction syndrome | ||||||||||||
End point description |
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific questionnaire for patients with gastrointestinal symptoms. The GSRS is a 15-item instrument designed to assess the symptoms associated with common GI disorders. Each item range from 1 to 3 and higher scores represent more discomfort. It has 4 subscales (Pain Syndrome, Dyspeptic syndrome, Indigestion Syndrome, Colon dysfunction syndrome).
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End point type |
Secondary
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End point timeframe |
Overall period
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Statistical analysis title |
Differences between groups | ||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
70
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.169 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Eradication rates | |||||||||||||||
End point description |
Porcentaje de pacientes que hayan erradicado mediante el test diagnóstico del test del aliento entre 4 y 8 semanas semanas tras la terminación del tratamiento con el probiótico o placebo.
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End point type |
Secondary
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End point timeframe |
At day 59
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Statistical analysis title |
Differences between groups | |||||||||||||||
Comparison groups |
Gastrus v Placebo
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Number of subjects included in analysis |
77
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
= 0.8745 | |||||||||||||||
Method |
Chi-squared | |||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Overall period
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Gastrus
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Reporting group description |
Gastrus (a dietary supplement containing Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 6475). The daily Gastrus dose was one tablet per day (2x108 UFC). It was administered from the first day of the eradicator treatment until completing 30 days of treatment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
The daily placebo dose was one tablet per day. It was administered from the first day of the eradicator treatment until completing 30 days of treatment. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |