Contraception
Conditions
Keywords
Drospirenone, Safety, INAS
Brief summary
The study compares the short- and long-term risks of a 24-day regimen of a drospirenone-containing oral contraceptive with the risks of established oral contraceptives in a study population that is representative for the actual users of the individual preparations.
Detailed description
Drospirenone is a novel progestogen with antiandrogenic and antimineralocorticoid properties. A large active post-marketing surveillance study has demonstrated that a 21-day regimen of 3mg drospirenone and 30mcg ethinylestradiol can be used safely for oral contraception. This study investigates the risks of short and long-term use of a 24-day regimen of drospirenone/ethinylestradiol in comparison to established OCs in a study population that is representative of the actual users of the individual preparations. INAS-OC is a prospective, controlled, non-interventional cohort study with two study arms: OCs containing drospirenone and OCs containing any other progestogen. The study was started in the USA in April 2005 and was extended to several European countries in September 2008 based on the launch status of the 24-day regimen. New users of an OC (starters, switchers without a pill intake break and recurrent users with a pill intake break \[same or different OC\]) are accrued by a network of prescribing physicians. Baseline and follow-up information are collected via a self-administered questionnaire. Data analysis will be based on life-table methods comparing the cohorts. All analyses will make allowance for confounding, using methods that will include multivariate techniques such as Cox regression.
Interventions
None listed
Sponsors
Bayer
Center for Epidemiology and Health Research, Germany
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
* First-ever OC users (starters) * Women switching OC use without a pill intake break (switchers) * Recurrent users with a pill intake break (recurrent users) * Women willing to participate in the active surveillance
Exclusion criteria
* Women who do not agree to participate * Long-term users
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | Within 60 months | Venous thromboembolism (VTE) hazard ratio for oral contraceptives containing both drospirenone (DRSP) and ethinylestradiol (EE) in a 24-day regimen or any oral contraceptive without DRSP. |
| Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | Within 60 months | Arterial thromboembolism (ATE) in women using oral contraceptives containing both drospirenone (DRSP) and ethinylestradiol (EE) in a 24-day regimen or any oral contraceptive without DRSP. Cox regression analysis was not carried out. In accordance to the analysis plan, hazard ratios were only to be calculated if a minimum of 5 confirmed events were available in each of the comparison groups. |
Countries
Germany
Participant flow
Recruitment details
Overall, 91,474 patients were recruited for the INAS-OC study. Of these, 6,365 participants were excluded due to protocol violations.
Participants by arm
| Arm | Count |
|---|---|
| OC DRSP-24d OCs containing DRSP (Yaz®, 24 day regimen ) | 15,542 |
| OC DRSP-21d OCs containing DRSP (Yasmin®, 21 day regimen) | 9,377 |
| OCs Non-DRSP Users of OCs containing other progestins | 60,190 |
| Total | 85,109 |
Baseline characteristics
| Characteristic | OC DRSP-21d | OCs Non-DRSP | OC DRSP-24d | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 1149 Participants | 7582 Participants | 2054 Participants | 10785 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 8227 Participants | 52608 Participants | 13488 Participants | 74323 Participants |
| Age, Continuous | 26.14 years STANDARD_DEVIATION 7.48 | 26.34 years STANDARD_DEVIATION 7.73 | 26.21 years STANDARD_DEVIATION 7.64 | 26.29 years STANDARD_DEVIATION 7.69 |
| Region of Enrollment Austria | 611 participants | 2945 participants | 738 participants | 4294 participants |
| Region of Enrollment Croatia | 68 participants | 371 participants | 509 participants | 948 participants |
| Region of Enrollment Germany | 1438 participants | 11207 participants | 922 participants | 13567 participants |
| Region of Enrollment Italy | 1427 participants | 2657 participants | 1644 participants | 5728 participants |
| Region of Enrollment Poland | 1457 participants | 3664 participants | 1169 participants | 6290 participants |
| Region of Enrollment Sweden | 398 participants | 1454 participants | 261 participants | 2113 participants |
| Region of Enrollment United States | 3978 participants | 37892 participants | 10299 participants | 52169 participants |
| Sex: Female, Male Female | 9377 Participants | 60190 Participants | 15542 Participants | 85109 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 7,264 | 0 / 5,605 | 0 / 39,316 | 0 / 4,070 | 0 / 28,854 |
| serious Total, serious adverse events | 583 / 7,264 | 499 / 5,605 | 2,740 / 39,316 | 254 / 4,070 | 1,756 / 28,854 |
Outcome results
Primary
Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs
Arterial thromboembolism (ATE) in women using oral contraceptives containing both drospirenone (DRSP) and ethinylestradiol (EE) in a 24-day regimen or any oral contraceptive without DRSP. Cox regression analysis was not carried out. In accordance to the analysis plan, hazard ratios were only to be calculated if a minimum of 5 confirmed events were available in each of the comparison groups.
Time frame: Within 60 months
Population: Study participants that were not excluded due to protocol violation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OC DRSP-24d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which transient ischemic attack (TIA) | 1 participants |
| OC DRSP-24d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | Total number of ATE | 4 participants |
| OC DRSP-24d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which peripheral ATE | 0 participants |
| OC DRSP-24d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which acute myocardial infarction | 2 participants |
| OC DRSP-24d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which ichemic stroke | 1 participants |
| OC DRSP-21d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which transient ischemic attack (TIA) | 0 participants |
| OC DRSP-21d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which ichemic stroke | 3 participants |
| OC DRSP-21d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which acute myocardial infarction | 0 participants |
| OC DRSP-21d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which peripheral ATE | 0 participants |
| OC DRSP-21d | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | Total number of ATE | 3 participants |
| OCs Non-DRSP | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which ichemic stroke | 15 participants |
| OCs Non-DRSP | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | Total number of ATE | 30 participants |
| OCs Non-DRSP | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which acute myocardial infarction | 10 participants |
| OCs Non-DRSP | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which transient ischemic attack (TIA) | 3 participants |
| OCs Non-DRSP | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which peripheral ATE | 2 participants |
| NOHC | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which peripheral ATE | 1 participants |
| NOHC | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | Total number of ATE | 2 participants |
| NOHC | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which transient ischemic attack (TIA) | 0 participants |
| NOHC | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which ichemic stroke | 0 participants |
| NOHC | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which acute myocardial infarction | 1 participants |
| No Use | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which ichemic stroke | 2 participants |
| No Use | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which transient ischemic attack (TIA) | 2 participants |
| No Use | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | Total number of ATE | 7 participants |
| No Use | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which peripheral ATE | 0 participants |
| No Use | Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | of which acute myocardial infarction | 3 participants |
Primary
Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs
Venous thromboembolism (VTE) hazard ratio for oral contraceptives containing both drospirenone (DRSP) and ethinylestradiol (EE) in a 24-day regimen or any oral contraceptive without DRSP.
Time frame: Within 60 months
Population: Study participants that were not excluded due to protocol violation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OC DRSP-24d | Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | 19 participants |
| OC DRSP-21d | Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | 16 participants |
| OCs Non-DRSP | Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | 101 participants |
| NOHC | Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | 7 participants |
| No Use | Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs | 19 participants |
Comparison: Tested null hypotheses: the VTE hazard ratio for DRSP(24d) vs. Non-DRSP is higher or equal to 295% CI: [0.5, 1.3]