E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000051 |
E.1.2 | Term | Abdominal aneurysm |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10002889 |
E.1.2 | Term | Aortic aneurysms and dissections |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To test whether ACE inhibition through Telmisartan reduces aneurysm progression |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
AAA measuring a maximum diameter of 35-49 mm on CTA |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |