E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Abdominal aortic aneurysms. Biomarkers related to diminished aneurysm wall strength. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000051 |
E.1.2 | Term | Abdominal aneurysm |
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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 |
Since rupture of an Abdominal Aortic Aneurysm (AAA) is potentially lethal, preventive surgical repair is warranted when the risk of rupture exceeds the risk of complications following surgery. Aneurysm rupture occurs when the forces acting on the aneurysm wall (stress) surpass aneurysm wall strength. Information on both wall stress and strength might therefore improve patient selection for prophylactic repair and reduce aneurysm related mortality. Although aneurysm wall stress calculations are possible, no in vivo method exists to determine aneurysm wall strength. This study is designed to identify possible in vivo biochemical (integrity of the extracellular matrix) and biological (inflammation; macrophage infiltration)markers related to aneurysm wall strength.
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E.2.2 | Secondary objectives of the trial |
1. To establish the relationship between Extracellular Matrix (ECM) degradation (loss of specific glucosaminoglycans and glycoproteins) and aneurysm wall tensile strength. 2. To correlate USPIO (Sinerem) uptake in infiltrated macrophages with aneurysm wall tensile strength. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Forty patients scheduled for conventional repair of an asymptomatic or symptomatic (non-ruptured) aneurysm. · Informed consent · Clinical condition allows MR imaging (USPIO group) · Preoperative CT (computer tomography)
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E.4 | Principal exclusion criteria |
· Ruptured aneurysm · Patient characteristics and aneurysm anatomy suitable for endovascular repair · Contraindication for MR imaging like metallic implants or claustrophobia (USPIO group). · Previous aortic aneurysm surgery · Severe cardiac co-morbidity (e.g. Chronic Heart Failure, Caronary artery disease).
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E.5 End points |
E.5.1 | Primary end point(s) |
Main study parameters/endpoints · Aneurysm wall tensile strength (maximal load before failure); N/mm · USPIO enhanced MRI, drop in relative signal intensity (SI); rSI = SIAAA/SIpsoas. · Histology, USPIO uptake in macrophages; number of macrophages containing iron on a 5-point scale; 0 no, 1 hardly any, 2 some, 3 many and 4 very many. · MMP tissue content; arbitrary units per mg proteins in the tissue extract · Glucosaminoglycans (Gag); mg of Gag-derived uronic acid/g of dry defatted tissue. · Glycoproteins; enzyme-liked immunosorbent Assay (ELISA), µg/ml · Collagen/elastin content; electon microscopy, number of intact fibres per unit area.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |