Clinical Trial Results:
A randomized controlled trial to evaluate the short-term efficacy and long-term health economic impact of a dietary intervention compared to pharmacotherapy with a musculotropic spasmolytic agent for newly diagnosed or newly treated irritable bowel syndrome in primary care.
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Summary
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EudraCT number |
2017-003258-18 |
Trial protocol |
BE |
Global end of trial date |
03 Jul 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Mar 2021
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First version publication date |
14 Mar 2021
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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 |
DOMINO
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04270487 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
UZLeuven
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Sponsor organisation address |
Herestraat 49, Leuven, Belgium, 3000
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Public contact |
Florencia Carbone, University Hospital Leuven, 0032 16345190, florencia.carbone@uzleuven.be
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Scientific contact |
Florencia Carbone, University Hospital Leuven, 0032 16345190, florencia.carbone@uzleuven.be
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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 |
15 Dec 2020
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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 |
03 Jul 2020
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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 |
The primary outcome is the improvement in IBS-Symptom Severity Score after 8 weeks of otilonium bromide compared to dietary intervention, with a 50-point drop being the established cut-off used in clinical trials. Based on our clinical experience and the available clinical data, we hypothesize that the dietary intervention will be superior to treatment with otilonium bromide 40 mg t.i.d. in improving IBS-SSS.
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Protection of trial subjects |
study participants were followed up by their GP.
Study participants who had not yet finished the study during the Covid-19-pandemic were able to perform V3 and V4 by telephone.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Jul 2018
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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 |
Belgium: 472
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Worldwide total number of subjects |
472
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EEA total number of subjects |
472
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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) |
432
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From 65 to 84 years |
40
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85 years and over |
0
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Recruitment
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Recruitment details |
IBS patients were recruited by GPs in primary care | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patients were eligible if they were newly diagnosed with IBS or newly to be treated for IBS. The diagnostic gold standard, in line with clinical practice, was the clinician’s diagnostic judgment. Also, patients who did not receive treatment with OB over the preceding 3 months, and who did not rece | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
overall study period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
Blinding implementation details |
patients were randomized to the diet or medication arm
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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lowering FODMAP diet | ||||||||||||||||||||||||||||||
Arm description |
The dietary arm in the study is the FODMAP lowering diet, also partially based on the dietary recommendations from the NICE and the British Dietetic Association. The diet was provided to the patients as a mobile phone application. The app included, among other tools, instructions to follow the diet, indications on what foods to avoid, to decrease ingestion or to use as alternatives. The possibility to acquire the diet on paper format was possible if the patient did not own a smart phone or tablet or if he had fail to download it. | ||||||||||||||||||||||||||||||
Arm type |
lowering FODMAP diet | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Otilonium Bromide | ||||||||||||||||||||||||||||||
Arm description |
The medication arm in the study will use Otilonium Bromide (40 mg t.i.d.) which is a well-established and well-tolerated treatment modality. In accordance with the pragmatic design of this trial, patients received the medication prescribed by the GP and were requested to buy it at the pharmacy. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Otilonium Bromide
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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 medication arm in the study will use Otilonium Bromide (40 mg t.i.d.). Patients randomized to the Otilonium Bromide arm, will take OB during 8 weeks (treatment phase). After the 8 week treatment phase they can continue the intake of OB during the follow up phase (16 weeks) or they can stop the intake of OB after the 8 week treatment phase and start another treatment during the FU phase (but they were not allowed to start a diet)
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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: Of the 472 included patients, 459 patients were randomized. 13 patients withdrew consent before randomization. |
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Baseline characteristics reporting groups
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Reporting group title |
overall study period
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Reporting group description |
459 patients were randomized | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
lowering FODMAP diet
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Reporting group description |
The dietary arm in the study is the FODMAP lowering diet, also partially based on the dietary recommendations from the NICE and the British Dietetic Association. The diet was provided to the patients as a mobile phone application. The app included, among other tools, instructions to follow the diet, indications on what foods to avoid, to decrease ingestion or to use as alternatives. The possibility to acquire the diet on paper format was possible if the patient did not own a smart phone or tablet or if he had fail to download it. | ||
Reporting group title |
Otilonium Bromide
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Reporting group description |
The medication arm in the study will use Otilonium Bromide (40 mg t.i.d.) which is a well-established and well-tolerated treatment modality. In accordance with the pragmatic design of this trial, patients received the medication prescribed by the GP and were requested to buy it at the pharmacy. | ||
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End point title |
treatment responder rate after 8 weeks | ||||||||||||
End point description |
IBS – symptom severity score scale (IBS-SSS) questionnaire: To assess the severity of IBS. The maximum achievable score is 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and >300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission.
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End point type |
Primary
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End point timeframe |
The primary outcome variable of the trial was treatment responder rate after 8 weeks. A responsive patient was defined as a patient with at least 50-point drop from baseline on the IBS IBS-SSS.
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Statistical analysis title |
Responder rate (low FODMAP diet vs OB) | ||||||||||||
Statistical analysis description |
The primary outcome variable of the trial was treatment responder rate after 8 weeks. A responsive patient was defined as a patient with at least 50-point drop from baseline on the IBS-SSS.
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Comparison groups |
lowering FODMAP diet v Otilonium Bromide
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Number of subjects included in analysis |
453
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
= 0.03 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Confidence interval |
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| Notes [1] - All analyses were conducted on an intention-to-treat (ITT) basis. For this analysis, the responder status was determined for all patients and the proportion of responders was compared between treatment arms using mixed effect logistic regression (MELR) which is effectively a mixed-model logistic regression in which treatment group is treated as a fixed effect and general practice as a random effect. |
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End point title |
Change in IBS-SSS (end - start) | ||||||||||||
End point description |
Treatment efficacy calculated using the change in IBS-symptom severity score scale (IBS-SSS).
The IBS-SSS is used to assess the severity of IBS. The maximum achievable score is 500. Mild, moderate and severe cases were indicated by scores of 75 to 175, 175 to 300 and >300 respectively. Controls scored below 75 and patients scoring in this range can be considered to be in remission.
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End point type |
Secondary
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End point timeframe |
Treatment efficacy after 8 weeks of treatment (low FODMAP diet vs Otilonium Bromide)
The change score for IBS-SSS was calculated as change from baseline to end of treatment phase.
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Statistical analysis title |
Change in IBS symptom severity score | ||||||||||||
Statistical analysis description |
The change score for IBS-SSS and all specified quantitative outcomes was calculated as change from baseline to end of therapy. Comparison of treatment groups employed linear regression with change score as the outcome variable and a single dummy-coded independent variable representing treatment group membership as the independent variable.
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Comparison groups |
lowering FODMAP diet v Otilonium Bromide
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Number of subjects included in analysis |
453
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Confidence interval |
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Adverse events information [1]
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Timeframe for reporting adverse events |
from signing the informed consent form until 30 days after the final study visit
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Adverse event reporting additional description |
The DOMINO trial was considered a low risk trial. Information regarding adverse events (AE) and serious adverse events (SAE) for the study treatments was indicated to GPs but collection of these data specific for this trial was not requested. Only serious adverse reactions (SAR) clearly related to OB were to be registered in the eCRF by the GP.
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
20
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| Frequency threshold for reporting non-serious adverse events: 1% | |||
| 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: The DOMINO trial was considered a low risk trial. For this reason, information regarding adverse events (AE) for the study treatments was indicated to GPs but collection of these data specific for this trial was not requested. It was the GP’s responsibility to determine all AEs and SAEs and manage them in the patient's medical record in accordance with standard clinical practice guidelines, and this for up to 30 days after the end of the trial. |
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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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15 Jun 2018 |
protocol versie 6 (04/04/2018);
ICF versie 3 (04/04/2018) (Nl + Fr);
eCRF: automatische e-mailnotificaties naar patiënten (Nl + Fr);
Toevoeging van de lijst met 80 huisartsen-onderzoekers **
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17 Jul 2018 |
protocol versie 7 (11/06/2018);
ICF versie 4 (11/06/2018) (Nl + Fr)
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18 Oct 2018 |
Toevoeging van de lijst met 21 huisartsen-onderzoekers |
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05 Mar 2019 |
Toevoeging van 6 bijkomende huisartsen-onderzoekers **
Toevoeging van GDPR informatieformulier voor patiënten (Nl + Fr) |
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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 | |||
