Metformin Therapy in Non-diabetic AAA Patients
Ključne riječi
Sažetak
Opis
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
Datumi
Posljednja provjera: | 09/30/2019 |
Prvo podneseno: | 03/28/2018 |
Predviđena prijava poslana: | 04/13/2018 |
Prvo objavljeno: | 04/24/2018 |
Posljednje ažuriranje poslano: | 10/21/2019 |
Posljednje ažuriranje objavljeno: | 10/23/2019 |
Stvarni datum početka studija: | 09/25/2018 |
Procijenjeni datum primarnog završetka: | 01/14/2022 |
Procijenjeni datum završetka studije: | 11/14/2022 |
Stanje ili bolest
Intervencija / liječenje
Drug: INVESTIGATIONAL DRUG
Drug: COMPARATIVE DRUG
Faza
Grupe ruku
Ruka | Intervencija / liječenje |
---|---|
Active Comparator: INVESTIGATIONAL DRUG oral metformin treatment with 2000Mg daily: Glucophage 500mg Tablet (2-0-2) daily for 1 year | Drug: INVESTIGATIONAL DRUG oral metformin Glucophage treatment 500 mg daily (2-0-2) for 1 year |
Placebo Comparator: COMPARATIVE DRUG Placebo matching M90 Oral Tablet treatment twice daily (2-0-2) for 1 year | Drug: COMPARATIVE DRUG Placebo Oral Tablet M90 treatment twice daily (2-0-2) for 1 year |
Kriterij prihvatljivosti
Dobni uvjeti za studiranje | 18 Years Do 18 Years |
Spolovi koji ispunjavaju uvjete za studij | All |
Prihvaća zdrave volontere | Da |
Kriteriji | 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 |
Ishod
Primarne mjere ishoda
1. AAA growth over 12 months in mm [12 months]
Sekundarne mjere ishoda
1. inflammation markers IL-6 [12 months]
2. glucose markers insulin and glucose [12 months]
3. neutrophil markers NGAL [12 months]
4. ineutrophil marker MPO [12 months]
5. neutrophil marker elastase [12 months]
6. AAA thrombus [12 months]