A multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: cortisone plus BMS or DES versus BMS alone to eliminate restenosis (CEREA-DES) - study design and rationale.

BACKGROUND: Several randomized trials and registries have shown a reduction of restenosis after coronary angioplasty with drug-eluting stents (DESs) compared with bare metal stents (BMSs). However, cost-efficacy analysis and long-term outcome of DESs compared to BMSs deserve further assessment. Moreover, concern has been raised regarding adverse clinical events occurring late after DES implantation, in particular, late stent thrombosis related to the suspension of dual antiplatelet therapy. The use of a short-cycle oral treatment with prednisone at immunosuppressive dose after BMS implantation has shown remarkable efficacy in reducing restenosis in nondiabetic patients, with very low additional cost and without the need for long-term dual antiplatelet therapy. Such results are however limited by small sample size. STUDY DESIGN: Cortisone plus BMS or DES versus BMS alone to Eliminate Restenosis is an independent, prospective, multicenter, randomized study. It will randomize 375 nondiabetic patients with coronary artery disease in three different arms to BMS (control group), DES (DES group) or BMS followed by a 40-day prednisone treatment (prednisone group). The DES and the prednisone groups will be compared to the control group to investigate the expected clinical advantage. The primary endpoint of the study is the event-free survival of cardiovascular death, myocardial infarction and recurrence of ischemia-needing repeated target vessel revascularization at 1 year. Secondary endpoints are the event-free survival analysis at 2 and 3 years, the restenosis rate at 9 months, and cost-effectiveness at 1, 2 and 3 years. SAMPLE SIZE: The expected primary endpoint rates are 90% for DESs and for prednisone-treated patients and 77% for BMSs. The study was designed as a superiority trial, to compare DES, and BMS and prednisone, with BMS alone. A sample size of 118 patients per group provides an 80% power, assuming a complete 12-month follow-up information available for each patient. To obviate for cases of drop out, the sample size was increased to 375 patients to be enrolled in five Italian hospitals. CONCLUSION: This study will provide a magnitude of the net clinical and economic benefits of DES and of the safety and efficacy of BMS and cortisone compared to the standard use of BMS alone in nondiabetic patients with coronary artery disease.

Shoulder acute pain in primary health care: is retraining GPs effective? The SAPPHIRE randomized trial: a cost-effectiveness analysis.

OBJECTIVES: To assess the cost-effectiveness of providing practical training to general practitioners (GPs) in shoulder problems, and administering a local anaesthetic (lignocaine) vs steroidal (cortisone) injection. METHODS: A cost-effectiveness analysis conducted alongside a cluster randomized trial with a factorial design, in general practices across five centres within the UK. A total of 155 participant GPs were randomized to receive training or no training with 200 participants randomized to either lignocaine or cortisone. Health care costs, quality-adjusted life years (QALYs) and incremental cost per QALY gained over 1 year estimated from a health system and a societal perspective were the main outcomes measured. RESULTS: Over 1 year, training GPs costs on average an additional pound sterling 211 (95% credibility interval - pound sterling 237, pound sterling 661) than no training and produces higher mean QALYs (0.075; -0.004, 0.154) per patient, yielding an incremental cost-effectiveness ratio of pound sterling 2813 per QALY gained for trained GPs. Over the same period of 1 year, lignocaine costs an average of pound sterling 122 more (- pound sterling 232, pound sterling 476) than cortisone and produces virtually no differential gain in mean QALYs (0.001; -0.068, 0.070), yielding an incremental cost per QALY gained of pound sterling 122,000 for lignocaine compared with cortisone. Across a range of cost-effectiveness thresholds, cortisone is as cost effective to inject as lignocaine. The probability that training is cost effective is above 0.95 at thresholds above pound sterling 20,000. CONCLUSIONS: Providing practical training to GPs about shoulder problems is cost effective and there is little uncertainty regarding this decision. The choice between lignocaine and cortisone is more uncertain and it is likely that there is significant value of further research to reduce this uncertainty. TRIAL REGISTRATION: The International Standard Randomised Controlled Trial Number is 58 537 244.