Metformin Therapy in Non-diabetic AAA Patients

Abdominal Aortic Aneurysm Clinical Trial

— MetAAA  

Official title:

A Prospective Randomized, Double Blind, Placebo-controlled, Safety and Efficacy Study of Metformin as add-on Therapy in Non-diabetic Patients With Abdominal Aortic Aneurysm (MetAAA Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03507413
• Other study ID #: 1479/2017
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: September 26, 2018
• Est. completion date: May 1, 2024

Study information

• Verified date: March 2024
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A prospective randomized, double blind, placebo-controlled, safety and efficacy study of metformin as add-on therapy in abdominal aortic aneurysm (AAA)

OBJECTIVES Primary Objective

• To demonstrate treatment efficacy of metformin in AAA in comparison to placebo or active comparator, as measured by growth of the AAA maximum diameter at 12 months Secondary Objectives

• To asses inflammatory cytokines and parameters of neutrophil activation in AAA in response to metformin treatment by glucose

• insulin

• Interleukin-6

• markers of neutrophil activation (MPO, elastase, NGAL)

Description:

DESIGN / PHASE Prospective, single-center, randomized, parallel group, double-blind, placebo controlled, phase IIa study STUDY PLANNED DURATION First patient First visit Year 1 1Q

Last patient First visit Year 2 4Q Last patient Last visit Year 3 2Q

CENTER(S)

• COUNTRY(IES) 1 center in 1 country Austria PATIENTS / GROUPS 170 patients in 2 groups 85 patients per group Randomization ratio 1:1 Stratification for hypertension, age, smoking habit, sex INCLUSION CRITERIA

• Infrarenal AAA of 3.0-4.9 cm maximum diameter EXCLUSION CRITERIA

• premenopausal female patients with a pregnancy possibility

• patients with diabetes

• indication for surgical AAA repair

• life expectancy <2 years

• contraindications for metformin, i.e. severely reduced kidney function (eGFR <30 ml/min), liver dysfunction, pancreatitis, alcohol abuse, malnutrition and decompensated heart failure STUDY PERIODS

• 1-2 year recruitment

• 1 year treatment

• 12 month follow-up INVESTIGATIONAL DRUG

Metformin:

initial dose: 500 mg 1-0-1 target dose: 1000 mg 1-0-1 COMPARATIVE DRUG /CONTROL CONDITION Placebo Initial and target dose: tablets 1-0-1 CONCOMITANT MEDICATION Allowed (standard of care) EFFICACY ENDPOINTS AAA growth (in maximum diameter) over 1 year TOLERABILITY / SAFETY surgery when AAA>5.5 cm for men, > 5 cm for women

Metformin Therapy for AAA Department of Surgery, Division of Vascular Surgery Medical University of Vienna, Austria

ENDPOINTS

adverse drug reactions liver insufficiency sustained reduction of kidney function with glomeral filtration rate <30 mg/dl (upon temporary renal insufficiency, infections, exsiccosis, diarrhea and lactic acidosis, metformin treatment will only be paused)

PHARMACOKINETIC / PHARMACODYNAMIC ENDPOINTS

• glucose

• insulin

• Interleukin-6

• markers of neutrophil activation (MPO, elastase, NGAL)

QUALITY OF LIFE / PHARMACOECONOMIC ENDPOINTS gastrointestinal discomfort (as assessed in the initial drop-out phase for patient exclusion)

STATISTICAL METHODOLOGY Primary Endpoint AAA growth at 12 months in mm

Null and alternative hypotheses:

H0: Metformin does not reduce AAA growth

H1: Metformin reduces AAA growth from mean 1.7 to 0.4 mm per year Type-I and -II errors:

Significance: 5% Power: 80% 1.7±3.3 mm (mean±SD) without Metformin and 0.4±2.3 mm (mean±SD) with Metformin treatment Sample size calculation 77 per group plus 16 patients drop out Total N= 170 Statistical methodology Main analysis set: per protocol Primary endpoint: analysis of covariance adjusted for baseline AAA diameter Pharmacokinetic endpoints: analysis of covariance adjusted for baseline value. Parametric assumptions will be graphically checked with histograms.

In case of non-normal distributions analysis of covariance will be performed after a logarithmic or rank transformation.

Safety endpoints will be described by cumulative incidence curves

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: May 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Infrarenal AAA of 3-4.9 cm maximum diameter

Exclusion Criteria:

• premenopausal female patients with a pregnancy possibility

• patients with diabetes

• indication for surgical AAA repair

• contraindications for metformin, i.e. severly reduced kidney function (eGFR <30 ml/min), liver dysfunction, pancreatitis, alcohol abusus, malnutrition and decompensated heart failure

Related Conditions & MeSH terms

• Abdominal Aortic Aneurysm
• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Abdominal

Intervention

Drug:
• Metformin Glucophage 500mg (IR) tablets M90
oral metformin Glucophage treatment 500 mg daily (2-0-2) for 1 year
• Placebo Oral Tablet
Placebo Oral Tablet M90 treatment twice daily (2-0-2) for 1 year

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Surgery, Division of Vascular Surgery	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	Merck Serono GmbH, Germany

Country where clinical trial is conducted

Austria, 

References & Publications (1)

minimale Endnote Formatierung der Refs im Word Dokument probieren!!!

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AAA growth over 12 months in mm	AAA maximum diameter in CT scan	12 months
Secondary	inflammation markers IL-6	inflammatory cytokines and parameters of neutrophil activation in patient plasma	12 months
Secondary	glucose markers insulin and glucose	inflammatory cytokines and parameters of neutrophil activation in patient plasma	12 months
Secondary	neutrophil markers NGAL	inflammatory cytokines and parameters of neutrophil activation in patient plasma	12 months
Secondary	ineutrophil marker MPO	inflammatory cytokines and parameters of neutrophil activation in patient plasma	12 months
Secondary	neutrophil marker elastase	inflammatory cytokines and parameters of neutrophil activation in patient plasma	12 months
Secondary	AAA thrombus	volume of AAA thrombus	12 months