Clinical Trial Results:
Misoprostol for the Healing of Small Bowel Ulceration in Patients with Obscure Blood Loss while Taking Low-Dose Aspirin or Non-Steroidal Anti-inflammatory Drugs [MASTERS Trial]
Summary
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EudraCT number |
2013-003187-31 |
Trial protocol |
GB |
Global end of trial date |
11 Oct 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Sep 2020
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First version publication date |
11 Sep 2020
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Other versions |
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Summary report(s) |
Friendly Summary - MASTERS Trial |
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 |
GN09CA403
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02202967 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
NHS Ayrshire & Arran
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Sponsor organisation address |
Simpson Street, Kilmarnock, United Kingdom, KA2 0BE
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Public contact |
Dr A S Taha, NHS Ayrshire & Arran, University Hospital Crosshouse, 44 1563827280, ali.taha1@btinternet.com
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Scientific contact |
Dr A S Taha, NHS Ayrshire & Arran, University Hospital Crosshouse, 44 1563827280, ali.taha1@btinternet.com
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Sponsor organisation name |
NHS Greater Glasgow & Clyde R&D Office, Dykebar Hospital
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Sponsor organisation address |
Grahamston Road, Paisley, United Kingdom, PA2 7DE
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Public contact |
Dr Maureen Travers, NHS Greater Glasgow & Clyde, 44 141 314 4012, Maureen.Travers@ggc.scot.nhs.uk
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Scientific contact |
Dr Maureen Travers, NHS Greater Glasgow & Clyde, 44 141 314 4012, Maureen.Travers@ggc.scot.nhs.uk
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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 |
28 Nov 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Oct 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Oct 2017
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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 |
In cases of iron deficiency anaemia or obscure gastrointestinal bleeding:
To assess the efficacy of an off-patent prostaglandin analogue, misoprostol, in healing of small bowel mucosal damage while continuing to take low-dose aspirin and/ or NSAIDs.
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Protection of trial subjects |
Exclusion of women of child-bearing potential if not using reliable contraceptive methods.
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Background therapy |
N/A | ||
Evidence for comparator |
Misoprostol is licensed for the healing of peptic ulcers caused by aspirin or non-steroidal anti-inflammatory drugs. Its effect on smal bowel ulcers is not known in users of these drugs. | ||
Actual start date of recruitment |
07 Jan 2016
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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 |
United Kingdom: 104
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Worldwide total number of subjects |
104
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EEA total number of subjects |
104
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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) |
80
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From 65 to 84 years |
24
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment dates: 7 January 2016 - 11 October 2017. | |||||||||
Pre-assignment
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Screening details |
We recruited patients (aged ≥18 years) with small bowel ulcers and taking aspirin, NSAIDs, or both for a minimum of 4 weeks. Eligible patients had evidence of obscure gastrointestinal bleeding (iron deficiency anaemia, a decrease in haemoglobin level of ≥20 × 10³ mg/L, or positive faecal occult blood test) and normal upper endoscopy and colonoscopy | |||||||||
Pre-assignment period milestones
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Number of subjects started |
104 | |||||||||
Number of subjects completed |
104 | |||||||||
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 | |||||||||
Blinding implementation details |
Randomisation was carried out using an interactive voice response system that allocated therapy packs per patient by telephone. The randomisation schedule was computer-generated, using the method of randomised permuted blocks of length 6 without stratification.
Patients, investigators, and assessors were masked to study treatment. Misoprostol and placebo capsules were identical in shape, colour, odour, and taste.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Active treatment | |||||||||
Arm description |
patients taking misoprostol | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Misoprostol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
200 ug four times daily
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Arm title
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Placebo group | |||||||||
Arm description |
Placebo | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
patients taking misoprostol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo group
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Reporting group description |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
patients taking misoprostol | ||
Reporting group title |
Placebo group
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Reporting group description |
Placebo |
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End point title |
Numbers of patients with fully healed ulcers and erosions at end of the trial | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The end of the study at 8 weeks
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Attachments |
Outcomes of MASTERS Trial |
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Notes [1] - Two completed patients were excluded from the final analysis because of protocol violation [2] - correct number |
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Statistical analysis title |
Fisher's exact test | |||||||||
Comparison groups |
Active treatment v Placebo group
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Number of subjects included in analysis |
102
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.0002 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
negative binomial regression models | |||||||||
Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
19.5 | |||||||||
upper limit |
53.9 |
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End point title |
Change in haemoglobin level | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
8 weeks
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Statistical analysis title |
Multivariable regression analysis | ||||||||||||
Comparison groups |
Active treatment v Placebo group
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Number of subjects included in analysis |
102
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.82 | ||||||||||||
Method |
multivariable regression | ||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.84 | ||||||||||||
upper limit |
4.24 |
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Adverse events information
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Timeframe for reporting adverse events |
End of trial at 8 weeks
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21
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Reporting groups
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Reporting group title |
Active treatment
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
N/A | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/29754836 |