Three-year efficacy, safety, and tolerability outcomes from a phase 3 study of a low-dose copper intrauterine device

Objectives: This study aimed to assess 3-year efficacy, safety, and tolerability of the Cu 175 mm² intrauterine device (IUD). Study design: This single-arm trial recruited participants at risk of pregnancy aged 17 to 45 years at 42 U.S. centers to receive a Cu 175 mm² IUD with a flexible nitinol frame. We assessed efficacy in participants aged ≤35 years at enrollment and assessed all other outcomes in the entire population. We calculated the Pearl Index (pregnancies/100 person-years) through 3 years as the primary efficacy outcome. The secondary outcomes included pregnancy percentages by life-table analysis, placement success, safety (adverse events), and tolerability. Results: Of 1620 enrollees, 1601 (98.8%) had successful IUD placement, with 1397 aged ≤35 years at enrollment. We observed a 1-year Pearl Index of 0.94 (95% CI 0.43–1.78) and 1-year and cumulative 3-year life-table pregnancy rates of 1.26% (95% CI 0.57%–1.95%) and 2.47% (95% CI 1.34%–3.60%), respectively. The most common adverse events included bleeding and pain. Over 3 years, 15.4% of participants discontinued due to bleeding or pain. Device expulsions occurred in 36 (2.2%) and 63 (3.9%) participants over 1 and 3 years, respectively. Eight related serious adverse events occurred, including five ectopic pregnancies and one each of uterine perforation, anemia, and uterine hemorrhage. One- and three-year continuation rates were 78.9% and 49.6%, respectively. Conclusions: These data support efficacy, safety, and tolerability of the Cu 175 mm² IUD during the first 3 years of use. Implications: In this Phase 3 trial, the investigational Cu 175 mm² demonstrated efficacy, safety, and tolerability with low rates of expulsion and discontinuation for bleeding and pain-related symptoms. This flexible, nitinol-framed, low-dose copper IUD comes preloaded and would expand contraceptive options beyond the single nonhormonal IUD currently available in the United States.