Retrospective Cohort Study on the Risk of Venous Thromboembolism with the use of combined oral contraceptives containing Chlormadinone Acetate/Ethinylestradiol and Levonorgestrel/Ethinylestradiol (RIVET-RCS)

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  CHLORMADINONE

  ETHINYLESTRADIOL

  LEVONORGESTREL
• Anatomical Therapeutic Chemical (ATC) code:
  (G03AA07) levonorgestrel and ethinylestradiol

  levonorgestrel and ethinylestradiol

  (G03AA15) chlormadinone and ethinylestradiol

  chlormadinone and ethinylestradiol
• Medical condition to be studied:
  Venous thrombosis

  Embolism venous

Population studied

• Age groups:
  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Estimated number of subjects:
  124000

Study design details

• Main study objective:
  The objective of this study is to compare the VTE risk (i.e. deep venous thrombosis and/or pulmonary embolism) of users of COCs containing CMA 2mg to users of COCs containing LNG 0.15mg, both combined with EE 30µg.
• Outcomes:
  The primary objective of this study is to assess the risk of venous thromboembolic events in the cohort of users of COCs containing 2 mg CMA/30 µg EE compared to 0.15 mg LNG/30 µg EE. The secondary objectives of this study are: ; - to assess the risk of venous thromboembolic events stratified by COC user type, age, BMI - to assess the risk of VTE in the sub-cohort of users of COCs containing CMA compared to LNG both combined with ≤30 µg EE. ; - to characterize the baseline risk of users of the two formulations.
• Data analysis plan:
  Baseline characteristics, including reproductive, contraceptive, and medical history, will be summarized using descriptive statistics. Inferential statistics will be based on the Cox proportional hazards models. Crude and adjusted HRs between the two cohorts of interest – 2mg CMA/30μg EE and 0.15mg LNG/30μg EE – will be calculated with 95%-confidence intervals. Four prognostic factors for VTE - age, BMI, current duration of use, and family history of VTE - will be included as covariates in the Cox model.