Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm.
Abdominal aortic aneurysm
Metformin
Placebo
Randomised controlled trial
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
27 Dec 2021
27 Dec 2021
Historique:
received:
28
09
2021
accepted:
03
12
2021
entrez:
28
12
2021
pubmed:
29
12
2021
medline:
30
12
2021
Statut:
epublish
Résumé
Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018.
Sections du résumé
BACKGROUND
BACKGROUND
Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms.
METHODS
METHODS
MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05).
DISCUSSION
CONCLUSIONS
Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design.
TRIAL REGISTRATION
BACKGROUND
Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018.
Identifiants
pubmed: 34961561
doi: 10.1186/s13063-021-05915-0
pii: 10.1186/s13063-021-05915-0
pmc: PMC8710921
doi:
Substances chimiques
Metformin
9100L32L2N
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
962Subventions
Organisme : National Health and Medical Research Council
ID : APP1180736
Organisme : Royal Australasian College of Surgeons
ID : N/A
Informations de copyright
© 2021. The Author(s).
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