Five-Year Phase 3 Efficacy and Safety Outcomes With a Low-Dose Copper Intrauterine Device

OBJECTIVE: To assess the 5-year efficacy and safety of a novel, nitinol-framed, low-dose copper intrauterine device (IUD) in an ongoing phase 3 trial. METHODS: In this single-arm trial, participants aged 17–45 years at risk for pregnancy were recruited to receive the Cu 175 mm 2 IUD with a flexible nitinol frame that comes preloaded with precut strings. Ongoing follow-up continues up to 8 years. We assessed the primary outcome of contraceptive efficacy in the population evaluable for pregnancy (those aged up to 35 years at enrollment) by Pearl Index, each year and cumulatively. Secondary outcomes included pregnancy percentage by life table analysis (Kaplan-Meier) and safety. RESULTS: The 1,620 enrollees included 1,601 (98.8%) who experienced successful IUD placement in the safety population and included 1,397 in the evaluable-for-pregnancy population, with 589 safety population participants completing 5 years of use by October 2024. We observed a 1-year Pearl Index of 0.94 (95% CI, 0.43–1.78) and a cumulative 5-year Pearl Index of 1.02 (95% CI, 0.68, 1.47). The cumulative 1-year table pregnancy rate was 1.3% (95% CI, 0.8–2.2%) and the 5-year rate was 4.1% (95% CI, 2.8–6.0%). The most common adverse events included bleeding and pain. In year 1, 140 participants (8.7%) exited the study for bleeding and pain concerns. This decreased to 13 of 673 participants (1.9%) in year 5 ( P <.001). Participants reported 76 (4.7%) device expulsions over 5 cumulative years. CONCLUSION: These data support the efficacy and safety of the Cu 175 mm 2 IUD through 5 years of use with low rates of expulsion. Participants report low and decreasing discontinuation rates over time for bleeding and pain-related symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03633799.