Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However during early months of use unscheduled vaginal bleeding is common sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS. METHODS: CDB-2914 150 mg in divided doses or placebo tablets were administered over three consecutive days starting on Days 21 49 and 77 after LNG-IUS insertion in a double-blind randomized controlled trial of women aged 19-49 years newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months and summarized across blocks as percentage days bleeding/spotting (BS%). RESULTS: Of 69 women randomized to receive CDB-2914 and 67 placebo 61 and 55 respectively completed the trial. BS% decreased with time in both arms but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001) so that a benefit of CDB-2914 in the 28 days after first treatment (-11% points 95% CI -19 to -2) converted to a disadvantage by 64 days after the third treatment (+10% points 95% CI 1-18). CONCLUSIONS: The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72.