This study presents an innovative decoupling solution designed to improve the seismic performance of infilled reinforced concrete (RC) frame structures. Previous experimental research by the authors confirmed the effectiveness of the decoupling system through a series of full-scale separate and combined in-plane and out-of-plane tests. In the present work, a simplified micro-model developed and realised in Abaqus is validated against three experimental tests and then employed in a comprehensive parametric study investigating the in-plane behaviour of RC frames with decoupled masonry infills featuring various opening types (windows, doors and partial infills) of different sizes and locations. The results demonstrate that the decoupling system successfully reduces adverse frame-infill interaction effects across all configurations. The first cracks in the decoupled masonry infills are typically observed at in-plane drifts exceeding the maximum design in-plane drift of 2.0 %. Meanwhile, the in-plane response of the frames remains largely unaffected. Finally, based on the comprehensive findings of the study, and in accordance with the second generation of Eurocode 8, practical guidelines are proposed for the design of the novel decoupling system to ensure efficient decoupling of masonry infills from the RC frames.