Multinational, multicentre, randomised, open-label study evaluating the impact of a 91-day extended regimen combined oral contraceptive, compared with two 28-day traditional combined oral contraceptives, on haemostatic parameters in healthy women

Abstract

Objectives To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 μg levonorgestrel [LNG]/30 μg ethinylestradiol [EE] for 84 days, followed by 10 μg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 μg LNG/30 μg EE [Treatment 2] or 150 μg desogestrel [DSG]/30 μg EE [Treatment 3], both with seven days’ hormone free), on several coagulation factors and thrombin formation markers.

Methods Randomised, open-label, parallel-group comparative study involving healthy women (18–40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months.

Results A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [− 18.3 pmol/L] > − 130 pmol/L).

Conclusions The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE.

Chinese Abstract

摘 要 目的 评估口服避孕药91天长周期疗法（150μg左炔诺孕酮[levonorgestrel，LNG]/30μg炔雌醇[ethinylestradiol，EE]84天，10μg EE 7天[治疗1]）与两种21/7常规方案（21天150μg LNG/30μg EE [治疗2]或150μg去氧孕烯[desogestrel，DSG]/30μg EE [治疗3]，两种治疗均有7天的间歇期）对凝血因子和凝血酶形成标记物的影响。

方法 关于18-40岁健康女性的随机、开放、平行组对照研究。主要研究终点为治疗6个月后凝血酶原片段F1+2与基线水平的变化。

结果 初步分析了187名受试者，治疗6个月后整个人群的F1+2平均水平上升。治疗1与治疗2的变化类似：最小二乘均数变化分别为170 pmol/L和158 pmol/L，但治疗3的变化明显大：最小二乘均数变化为592 pmol/L。治疗1的止血效果与治疗2的相似，但不比治疗3差（95%置信区间下限[ -18.3 pmol/L] ＞ -130 pmol/L）。

结论 LNG/EE两种治疗方案对F1+2的影响相似，LNG/EE长周期方案与DSG/EE常规方案相比无差别。

Keywords:

• Coagulation
• Combined oral contraceptives
• Desogestrel
• Haemostatic
• Levonorgestrel

ACKNOWLEDGEMENTS

Nicole Cooper of MedVal Scientific Information Services, LLC, provided medical writing and editorial assistance. This manuscript was prepared according to the International Society for Medical Publication Professionals’ ‘Good Publication Practice for Communicating Company-Sponsored Medical Research: the GPP2 Guidelines’ and the International Committee of Medical Journal Editors’ ‘Uniform Requirements for Manuscripts Submitted to Biomedical Journals’. Funding to support the preparation of this manuscript was provided to MedVal Scientific Information Services, LLC, Skillman, NJ by Teva Women's Health, Inc.

Funding: This study was sponsored by Teva Branded Pharmaceutical Products, R&D, Inc.

Declaration of interest: Dr Nappi: lecturer, advisory board member, and consultant for Bayer-Schering Pharma, Eli Lilly, Gedeon Richter, HRA Pharma, Merck Sharpe & Dohme, Novo Nordisk, Pfizer Inc, Shionogi, Teva/Theramex; Dr Paoletti: advisory board member for Bayer, Teva/Theramex, Gedeon Richter; Dr Howard and Dr Weiss are employees of Teva Global Medical Affairs; Ms Ricciotti is an employee of Teva Branded Pharmaceutical Products, R&D, Inc. The authors alone are responsible for the content and the writing of the paper.