Challenging Issues in Clinical Trial Design: Part 4 of a 4-Part Series on Statistics for Clinical Trials.

As a sequel to last week's paper on the fundamentals of clinical trial design, this paper tackles related controversial issues: noninferiority trials, the value of factorial designs, the importance and challenges of strategy trials, Data Monitoring Committees (including when to stop a trial early), and the role of adaptive designs. All topics are illustrated by relevant examples from cardiology trials

Design of Major Randomized Trials: Part 3 of a 4-Part Series on Statistics for Clinical Trials.

This paper provides practical guidance on the fundamentals of design for major randomized controlled trials. Topics covered include the choice of patients, choice of treatment and control groups, choice of primary and secondary endpoints, methods of randomization, appropriate use of blinding, and determination of trial size. Insights are made with reference to contemporary major trials in cardiology

Quantification and Impact of Untreated Coronary Artery Disease After Percutaneous Coronary Intervention the Residual SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) Score

Objectives the purpose of this study was to quantify the extent and complexity of residual coronary stenoses following percutaneous coronary intervention (PCI) and to evaluate its impact on adverse ischemic outcomes.Background Incomplete revascularization (IR) after PCI is common, and most studies have suggested that IR is associated with a worse prognosis compared with complete revascularization (CR). However, formal quantification of the extent and complexity of residual atherosclerosis after PCI has not been performed.Methods the baseline Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (bSS) from 2,686 angiograms from patients with moderate-and high-risk acute coronary syndrome (ACS) undergoing PCI enrolled in the prospective ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial was determined. the SS after PCI was also assessed, generating the residual SS (rSS). Patients with rSS >0 were defined as having IR and were stratified by rSS tertiles, and their outcomes were compared to the CR group.Results the bSS was 12.8 +/- 6.7, and after PCI the rSS was 5.6 +/- 2.2. Following PCI, 1,084 patients (40.4%) had rSS = 0 (CR), 523 (19.5%) had rSS >0 but 2 but 8. Age, insulin-treated diabetes, hypertension, smoking, elevated biomarkers or ST-segment deviation, and lower ejection fraction were more frequent in patients with IR compared with CR. the 30-day and 1-year rates of ischemic events were significantly higher in the IR group compared with the CR group, especially those with high rSS. By multivariable analysis, rSS was a strong independent predictor of all ischemic outcomes at 1 year, including all-cause mortality (hazard ratio: 1.05, 95% confidence interval: 1.02 to 1.09, p = 0.006).Conclusions the rSS is useful to quantify and risk-stratify the degree and complexity of residual stenosis after PCI. Specifically, rSS >8.0 after PCI in patients with moderate-and high-risk ACS is associated with a poor 30-day and 1-year prognosis. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes; NCT00093158) (J Am Coll Cardiol 2012;59:2165-74) (C) 2012 by the American College of Cardiology Foundationsanofi-aventisMedicines CompanyAbbott VascularBristol-Myers SquibbAstraZenecaColumbia Univ, Med Ctr, Cardiovasc Res Fdn, New York, NY 10022 USAUniv Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, CanadaUniv Bologna, Inst Cardiol, Bologna, ItalyUniversidade Federal de São Paulo, Hosp Israelita Albert Einstein, Sau Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Sau Paulo, BrazilMt Sinai Med Ctr, New York, NY 10029 USAErasmus Univ, Thoraxctr, NL-3000 DR Rotterdam, NetherlandsUniversidade Federal de São Paulo, Hosp Israelita Albert Einstein, Sau Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Sau Paulo, BrazilWeb of Scienc

734-4 Can Intracoronary Ultrasound Improve PTCA Results?: Preliminary Core Lab Ultrasound Analysis from the CLOUT Pilot Study

The CLOUT Pilot Study hypothesis is that intracoronary ultrasound (ICUS) guidance can maximize the potential of balloon angioplasty through the safe application of carefully chosen oversized balloons. PTCA was performed until success was obtained using standard angiographic criteria. ICUS was then performed and, based on the degree of reference segment disease, balloons were upsized from 0.25 to 0.75mm (mean 0.4mm) regardless of the angiographic results. There have been no complications using this strategy in the initial 14 of a planned 100 patients. ICUS measures were performed using semiautomated programs at a core laboratory.ResultsIn the reference segment, ICUS revealed a mean lumen diameter of 2.60±0.35mm and plaque thickness of 0.78±0.11mm; on average 54.75±11.05% of the reference vessel was occupied by atheroma. At initial ICUS evaluation after angiographically successful PTCA, the lesion had a minimal lumen diameter (MLD) of 1.78±0.22mm and lumen area of 3.14±0.88mm2. Following balloon upsizing, the lesion MLD increased to 1.95±0.15mm (8.7% gain, p<0.02) and lumen area to 3.76±0.63mm2(16.7% gain, p<0.01). When compared to the reference segment lumen area, the lesional %lumen area reduction improved from 38.14±16.74% to 25.91±12.17% (p<0.01). Lumen improvement occurred primarily by expansion of the total vessel area (12.08±3.01mm2to 12.51±3.11 mm2, p=ns). As expected, there was a large degree of residual atheroma (68.62±7.47% cross sectional narrowing). After routine PTCA, only 5 of 12 patients reached a target MLD of 75% of the reference lumen diameter. Following balloon upsizing, 8 of 12 had reached this criteria.ConclusionsICUS guided balloon upsizing based on the degree of reference segment disease may be safely performed and results in significant improvement in luminal cross sectional area above that achieved by angiographic guidance alone. This may potentially lower restenosis rates if these initial gains are sustained long term