Randomized trial to evaluate contraceptive efficacy, safety and acceptability of a two-rod contraceptive implant over 4 years in the Dominican Republic.

OBJECTIVE: Sino-implant (II) is a contraceptive implant that had a commodity price one-third of the competing products a decade ago. To make Sino-implant (II) more widely available, we conducted a trial to collect safety and efficacy data required for World Health Organization (WHO) prequalification, a quality standard allowing global donors to procure a pharmaceutical product. STUDY DESIGN: This was a randomized controlled trial allocating 650 participants to either Sino-implant (II) or Jadelle®. Participants were seen at 1 and 6 months, and then semiannually. The primary efficacy measure was the pregnancy Pearl Index [number of pregnancies per 100 women-years (WY) of follow-up] in the Sino-implant (II) group during up to 4 years of implant use. RESULTS: For the primary outcome, Sino-implant (II) had a 4-year Pearl Index of 0.74 (95% confidence interval, 0.36-1.37) compared to 0.00 (95% confidence interval, 0.00-1.04) for Jadelle®. The Sino-implant (II) pregnancy rate was significantly higher in the fourth year (3.54 per 100 WY) than in the first 3 years combined (0.18 per 100 WY; p <.001). Total levonorgestrel concentrations were equivalent between groups at month 12, but were 19%, 22% and 32% lower in the Sino-implant (II) group at months 24, 36 and 48, respectively (p <.001 at each time point). Safety and acceptability of the two products were similar, while providers documented significantly higher breakage rates during removal of Sino-implant (II) (16.3% vs. 3.1%; p <.001). CONCLUSION: Based on these results, WHO prequalified Sino-Implant (II) with a 3-year use label in June 2017, 2 years shorter than the 5-year duration of Jadelle®. IMPLICATIONS: WHO prequalification allows global donors to procure Sino-implant (II), which means women in many low resource countries will have greater access to highly effective and acceptable contraceptive implants. Our study noted important clinical differences, including shorter duration of high effectiveness with Sino-implant (II) when compared to the other available two-rod system, Jadelle®. Introduction strategies should include appropriate training on these differences.

Cohort study to evaluate efficacy, safety and acceptability of a two-rod contraceptive implant during third, fourth and fifth year of product use in China.

OBJECTIVE: Sino-implant (II) is a contraceptive implant approved for 4 years of use in China. We evaluated the contraceptive efficacy during the third, fourth and fifth year, and assessed additional pharmacokinetics (PK), safety, and acceptability endpoints. STUDY DESIGN: We enrolled a cohort of 255 current Sino-Implant (II) users entering their third year and a second cohort of 243 users entering their fourth year. We followed these two cohorts for 12 and 24 months, respectively. To characterize PK endpoints (i.e. levonorgestrel (LNG), sex hormone binding globulin and free LNG index) over 5 years, we collected blood samples in a subset of 50 participants we followed during the third, fourth and fifth year. We also enrolled small cohorts (n = 20) of Sino-implant (II) users entering their sixth month and second year and followed them each for up to 6 months. Our primary efficacy measures were the pregnancy Pearl Indices during Year 3 and 4. Secondary objectives included assessments of PK, safety, acceptability and efficacy in the fifth year. RESULTS: We recorded four pregnancies, with a higher pregnancy rate during Year 3 [1.34 (95% CI: 0.28-3.93)] than Year 4 [0.44 (95% CI: 0.01-2.47)] or Year 5 [0.00 (95% CI: 0.00-2.02)]. The overall pregnancy rate for the third, fourth and fifth years of product use was 0.63 per 100 WY; 95% CI: (0.17-1.62). Mean LNG concentrations remained well above 200 pg/mL (Year 3 = 280.9; Year 4 = 233.6; Year 5 = 270.6). Most participants (93.7%) described their bleeding pattern as acceptable. CONCLUSION: Sino-implant (II) is a highly effective contraceptive method in this population of Chinese women over 5 years. IMPLICATIONS: Sino-implant (II) is a highly effective contraceptive method with an estimated Pearl Index of less than 1% over the third, fourth and fifth years of use in a population of Chinese women of reproductive age.