Abdominal aortc aneurysm MedDRA version: 14.1 Level: LLT Classification code 10000051 Term: Abdominal aneurysm System Organ Class: 10047065 - Vascular disorders MedDRA version: 14.1 Level: HLT Classification code 10002889 Term: Aortic aneurysms and dissections System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Trade Name: Telmisartan
Product Name: Telmisartan
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: TELMISARTAN
CAS Number: 144701-48-4
Concentration unit: mg milligram(s)
Concentration type: eq
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: AAA measuring a maximum diameter of 35-49 mm on CTA Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 320
Exclusion criteria
Exclusion criteria: Indication for AAA repair according to the treating physician or expectation that this will be revised within the next year High likelihood of non-compliance with treatment over 24 months Contraindications to study treatment, including: renal impairment (i.e. creatinine >1.5x upper limit of normal [ULN]), known significant renal stenosis (>70%) of one or both renal arteries, chronic liver disease (i.e. cirrhosis or hepatitis) or abnormal liver function (i.e. ALT 1.5xULN), electrolyte imbalance and gout No current or planned usage of an AT1 blocker or ACE inhibitors
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test whether ACE inhibition through Telmisartan reduces aneurysm progression;Secondary Objective: Not applicable;Primary end point(s): The primary outcome measure will be the rate of growth of the AAAs estimated using total infrarenal volume and maximum orthogonal AAA diameter measured at entry, 12 & 24 months from the CTA. We have selected CTA as our primary outcome modality since we have found this assessment to be more sensitive to change and accurate in our preliminary cohort (see Table 2; volume changes by cm3). Current CTA protocols expose the participants to low dose radiation only. In a recent cohort of 12 participants assessed by CTA the median radiation dose was 20mGy (range 14-28mGy). Since we plan to obtain only 3 CTAs per participant over a 2 year period, the overall dose will be low. ;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): I. Change in maximum infrarenal AAA diameter on repeat ultrasound at entry, 6, 12, 18 & 24 months; II. Change in serum OPG, OPN, MMP-9 and TGF?-1 on repeated samples over 24 months; III. Quality of life assessed by the SF36 (Quality of Life) questionnaire completed at entry, 12 & 24 months, which we have previously validated for use in elderly participants [62-64]; IV. There is increasing evidence that the efficacy of medications vary between individuals, with a growing interest in pharmacogenetics [75]. We have previously shown an association between genetic polymorphism in AT1 and AAA [43]. We will assess the presence of the AT1 1166C single nucleotide polymorphism (previously consistently associated with AAA) in recruited participants. This will enable us to analyse the impact of this polymorphism on response to telmisartan. V. Changes in mRNA expression as previously described [88, 89]. This will allow us to identify precisely how participants are responding to the treatment. This may ultimately identify which participants are more responsive to the medication and should be treated. ;Timepoint(s) of evaluation of this end point: 6, 12, 18 & 24 months; | — |
Countries
Australia, Netherlands, United States
Contacts
Public ContactDept. Vascular Surgery
Leiden University Medical Center
Outcome results
None listed