Ignite Creation Date:
2024-05-06 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 12:44 PM
Study NCT ID:
NCT03507413
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-03-28
First Post:
2018-03-29
Brief Title:
Metformin Therapy in Non-diabetic AAA Patients
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
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
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MetAAA
Brief 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
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
Detailed 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
CENTERS
COUNTRYIES 1 center in 1 country Austria PATIENTS GROUPS 170 patients in 2 groups 85 patients per group Randomization ratio 11 Stratification for hypertension age smoking habit sex INCLUSION CRITERIA
Infrarenal AAA of 30-49 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 ie severely reduced kidney function eGFR 30 mlmin 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 AAA55 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 mgdl 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 17 to 04 mm per year Type-I and -II errors
Significance 5 Power 80 1733 mm meanSD without Metformin and 0423 mm meanSD 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
Last patient First visit Year 2 4Q Last patient Last visit Year 3 2Q
CENTERS
COUNTRYIES 1 center in 1 country Austria PATIENTS GROUPS 170 patients in 2 groups 85 patients per group Randomization ratio 11 Stratification for hypertension age smoking habit sex INCLUSION CRITERIA
Infrarenal AAA of 30-49 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 ie severely reduced kidney function eGFR 30 mlmin 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 AAA55 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 mgdl 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 17 to 04 mm per year Type-I and -II errors
Significance 5 Power 80 1733 mm meanSD without Metformin and 0423 mm meanSD 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None