Clinical Trial Results:
The effect of on demand versus continuous use of proton pump inhibitors on reflux symptoms, quality of life and self-rated health in patients with gastro-oesophageal reflux disease
Summary
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EudraCT number |
2014-001314-25 |
Trial protocol |
NL |
Global end of trial date |
09 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Feb 2023
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First version publication date |
10 Feb 2023
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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 |
KIANANDR140701
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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 |
Karolinska Institutet
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Sponsor organisation address |
Alfred Nobels allé 12, Huddinge, Sweden,
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Public contact |
Centre for Family Medicine, Karolinska Institutet, 46 0852488000, villvetamer@cefam.se
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Scientific contact |
Anna Andreasson, Centre for Family Medicine, Karolinska Institutet, 46 0852488000, anna.andreasson@su.se
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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 |
Interim
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Date of interim/final analysis |
09 Mar 2016
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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 |
09 Feb 2016
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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 |
1. To evaluate whether there is a difference in symptom relief in patients prescribed PPI on demand and patients prescribed continuous use of PPI.
2. To evaluate whether the use of electronic tools developed to facilitate clinical trials in primary care result in a higher recruitment rates than paper-based data collection.
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Protection of trial subjects |
Trial subjects were primary care patients that received one of two approved treatments for gastroesophageal reflux disease. The trial subjects were asked to fill out a questionnaire about drug consumption and health related quality of life (QoL), that took approximately 20 minutes each, total 40 minutes. No specific measures were put in place to protect the trial subjects, as they recieved standard care and the questionnaire was brief and the content should not cause pain or distress.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 May 2015
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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 |
Netherlands: 17
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Country: Number of subjects enrolled |
Greece: 248
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Country: Number of subjects enrolled |
United Kingdom: 14
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Country: Number of subjects enrolled |
Poland: 336
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Worldwide total number of subjects |
615
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EEA total number of subjects |
615
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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) |
615
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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 between May and December 2015. 36 primary care centres participated in the study: 8 in Greece, 10 in Poland, 8 in the Netherlands and 10 in the UK. | |||||||||||||||
Pre-assignment
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Screening details |
Eligible patients were adults 18 to 65 years of age diagnosed with GERD and requiring PPI treatment i.e. symptoms at least 2 times a week negatively influencing quality of life that had previously been prescribed and obtained symptom relief from PPI use (PPI treatment responders). | |||||||||||||||
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 |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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On demand | |||||||||||||||
Arm description |
This patient group was given on demand use of PPI (20 mg Omeprazole on demand, maximum daily intake two pills i.e. 40 mg). | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Omeprazole
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
20 mg Omeprazole on demand, maximum daily intake two pills i.e. 40 mg
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Arm title
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Continous use | |||||||||||||||
Arm description |
This patient group was given continous prescription of PPI (20 mg Omeprazole daily). | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Omeprazole
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
20 mg Omeprazole daily
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Baseline characteristics reporting groups
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Reporting group title |
On demand
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Reporting group description |
This patient group was given on demand use of PPI (20 mg Omeprazole on demand, maximum daily intake two pills i.e. 40 mg). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Continous use
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Reporting group description |
This patient group was given continous prescription of PPI (20 mg Omeprazole daily). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
On demand
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Reporting group description |
This patient group was given on demand use of PPI (20 mg Omeprazole on demand, maximum daily intake two pills i.e. 40 mg). | ||
Reporting group title |
Continous use
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Reporting group description |
This patient group was given continous prescription of PPI (20 mg Omeprazole daily). |
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End point title |
GERD symptom burden | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline to follow up 8 weeks later
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Statistical analysis title |
Difference in GERD symptom burden | ||||||||||||
Statistical analysis description |
Difference in GERD symptom burden between on demand PPI users and continuous PPI users at follow-up visit
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Comparison groups |
Continous use v On demand
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Number of subjects included in analysis |
459
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||
P-value |
= 0.84 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Confidence interval |
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Notes [1] - Mixed effect regression model with interaction time treatment to test for treatment effect |
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End point title |
SF-12 physical health score | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline to follow up 8 weeks later
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Statistical analysis title |
Difference in physical health QoL score | ||||||||||||
Statistical analysis description |
Difference in physical health QoL score between on demand PPI users and continuous PPI users at follow-up visit
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Comparison groups |
On demand v Continous use
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Number of subjects included in analysis |
459
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [2] | ||||||||||||
P-value |
= 0.46 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Confidence interval |
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Notes [2] - Mixed effect regression model with interaction time treatment to test for treatment effect |
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End point title |
SF-12 mental health score | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline to follow up 8 weeks later
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Statistical analysis title |
Difference in mental health QoL score | ||||||||||||
Statistical analysis description |
Difference in mental health QoL score between on demand PPI users and continuous PPI users at follow-up visit
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Comparison groups |
On demand v Continous use
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Number of subjects included in analysis |
459
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||
P-value |
= 0.17 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Confidence interval |
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Notes [3] - Mixed effect regression model with interaction time treatment to test for treatment effect |
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End point title |
Self-rated health | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From baseline to follow up 8 weeks later
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Statistical analysis title |
Difference in self-rated health | ||||||||||||
Statistical analysis description |
Difference in self-rated health between on demand PPI users and continuous PPI users at follow-up visit
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Comparison groups |
On demand v Continous use
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Number of subjects included in analysis |
459
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [4] | ||||||||||||
P-value |
= 0.61 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Confidence interval |
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Notes [4] - Mixed effect regression model with interaction time treatment to test for treatment effect |
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End point title |
PPI use last week | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At follow up (8 weeks)
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Statistical analysis title |
Difference in PPI intake | ||||||||||||
Statistical analysis description |
Difference in PPI intake at follow-up visit
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Comparison groups |
On demand v Continous use
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Number of subjects included in analysis |
459
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Analysis specification |
Post-hoc
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Analysis type |
non-inferiority [5] | ||||||||||||
P-value |
= 0.33 | ||||||||||||
Method |
Regression, Linear | ||||||||||||
Confidence interval |
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Notes [5] - Mixed effect regression model with interaction time treatment to test for treatment effect |
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Adverse events information [1]
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Timeframe for reporting adverse events |
13/05/2015 – 31/12/2015
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Assessment type |
Non-systematic | |||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Free text | |||||||||||||||
Dictionary version |
n/a
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Reporting groups
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Reporting group title |
On demand
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Reporting group description |
This patient group was given on demand use of PPI (20 mg Omeprazole on demand, maximum daily intake two pills i.e. 40 mg). | |||||||||||||||
Reporting group title |
Continous use
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Reporting group description |
This patient group was given continous prescription of PPI (20 mg Omeprazole daily). | |||||||||||||||
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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: There were no non-serious adverse events recorded for these results. |
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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. | |||
Limitations include missing data on symptoms and health related quality of life of the participants who used the TRANSFoRm tool to complete questionnaires, however, this was largely due to a technical issue and data loss can be assumed to be random. |