PICCOLETO III is a multicenter, randomized clinical trial that will assess the efficacy of two different drug-coated balloons (DCB), paclitaxel and sirolimus DCB compared to drug-eluting stents (DES), in patients with chronic total occlusions (CTO). The outcomes of interest will be evaluated over a period of up to 5 years, providing valuable long-term data on the use of these treatments in patients with complex coronary lesions.