E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
The peri-procedural use of oral corticosteroids in elective/acute patients undergoing percutaneous coronary intervention for coronary artery disease reduces the incidence of in-segment re-stenosis. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
In our original submission we stated that quantitative coronary angiographic measurements will be made before pre-dilation (baseline), after the stenting procedure and at follow up angiography using the Philips Inturis system. We wish to extend this by undertaking a more detailed assessment using intravascular ultrasound (IVUS). This technique has been extensively validated in angiographic assessment and has been crucial to our understanding of the mechanisms of stent loss during follow-up (Mintz GS 2005). We believe the additional use of IVUS will allow us to better assess the relationship between systemic inflammation, stent composition and the effect of oral steroid therapy in influencing arterial re-stenosis.
Atheromatous plaque volume in the stented arterial segment will be quantified by IVUS and volume calculated using a well validated edge-detection algorithm as previously described (von Birgelen, et al.,1997; von Birgelen MD, et al., 1997). Briefly, the coronary artery is cannulated with a guiding catheter, and a 3.2F 30-MHz IVUS imaging catheter (Scimed, Boston Scientific Corp) advanced into the artery. IVUS examination of the stented artery is performed at 0.5 mm/s with a motorised pullback device (Boston Scientific Corp). Computerized 3D reconstructions of the stented segments will be performed offline by a single blinded operator using the TomTec computer system (Echoscan, TomTec Imaging Systems) (Newby, et al., 2001). All patients will be invited to return at 6 months for a repeat angiogram and IVUS study to quantify volume of in-stent re-stenosis.
Sample size calculation based on the presumption that a difference of 0.25 mm in Minimal Luminal Diameter (MLD) at 6 months is clinically relevant. With a standard deviation of 0.5 mm, a sample size of 64 patients per group (128 in total) will achieve a power of 0.8 at a significance level of 0.05 (Oemrawsingh et al, Circulation 2003;107:62).
References Mintz GS 2005. Mechanisms, prevention, and treatment of re-stenosis. In: Mintz GS. Intracoronary Ultrasound. London: Taylor and Francis, 2005:299–400.
Newby DE, et al (2001). Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis. Circulation 103:1936-1941. von Birgelen MD C, et al (1997). Variations of Remodeling in Response to Left Main Atherosclerosis Assessed With Intravascular Ultrasound In Vivo. American Journal of Cardiology 80:1408-1413. von Birgelen C, et al (1997) ECG-Gated Three-dimensional Intravascular Ultrasound : Feasibility and Reproducibility of the Automated Analysis of Coronary Lumen and Atherosclerotic Plaque Dimensions in Humans. Circulation 96:2944-2952.
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E.3 | Principal inclusion criteria |
Any patient awaiting percutaneous coronary intervention for symptomatic coronary artery disease (elective or acute). Documented myocardial ischaemia. Coronary angiography demonstrating at least a 50% reduction of the luminal diameter in at least one native coronary artery (as measured by quantitative computerised angiography).
Ammendment: Any lesion for which the operator (interventional consultant cardiologist) feels a non-drug eluting stent is appropriate |
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E.4 | Principal exclusion criteria |
Left Main Stem stenosis PCI for ST elevation myocardial infarction Steroid therapy within 30-days of study enrolment. Contraindication to corticosteroid use. Previous inclusion in this study. Non-cardiac disease likely to cause death within 6-months. (Proposed use of a drug eluting stent.) Ammendment: Proposed use of a drug eluting stent (in the study lesion(s)). Inter-hospital transfers from Cumbria.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end point Angiographically documented in-segment re-stenosis.
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.3 |
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 | 2 |
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 | Yes |
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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Once the last patient has attended the last visit OR as determined by data monitoring committee stopping rules. |
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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 | 7 |
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 | 0 |
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 |