Arterial Thromboembolism, Breast Cancer, Venous Thromboembolism
Conditions
Keywords
Contraception, Thromboembolism, Breast Cancer
Brief summary
The objective of this study is to characterize and compare the risks of long-term use of oral contraceptives containing drospirenone and of other established oral contraceptives.
Detailed description
The LASS Study is a large, multinational, prospective, controlled, non-interventional, long-term cohort study that follows a series of cohorts. The cohorts consist of new users (first-ever users, switchers and restarters) of three different groups of oral contraceptives (OCs): OCs containing drospirenone (DRSP), OCs containing levonorgestrel (LNG) and OCs containing other progestogens. A non-interference approach is used to provide standardized, comprehensive, reliable information on these groups of OCs under routine medical conditions. The main clinical outcomes of interest for the long-term follow-up are arterial and venous thromboembolism as well as breast cancer. Regular, active contacts with the cohort members (=active surveillance) provide all necessary information on health-related events or changes in health status. The study is based on the existing long-term EURAS cohorts who are still in follow-up. LASS succeeds EURAS and prolongs the follow-up period for another five years. Total follow-up time of members of the long-term cohorts will be between 6 and 10 years. By means of annual contacts almost all relevant clinical outcomes will be captured. This will be accomplished by contacting the relevant physicians and by reviewing relevant source documents in the case of relevant clinical outcomes.
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
* Women who are prescribed an oral contraceptive and who are new users (first-ever users, switchers or restarters) of the formulation
Exclusion criteria
* Women who do not consent to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arterial Thromboembolism | Within 10 years | Arterial thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens. |
| Venous Thromboembolism | Within 10 years | Venous thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens. |
| Breast Cancer | Within 10 years | Breast cancer associated with the use of hormonal contraceptives either containing both drospirenone (DRSP) and ethinylestradiol (EE), levonorgestrel (LNG) or any other hormonal contraceptive without DRSP. |
Countries
Germany
Participant flow
Recruitment details
In the LASS study, 59,510 women were recruited overall. Of these, 836 participants were excluded due to protocol violation (e.g. patient did not start OC use). Furthermore, 371 patients started treatment with non-oral contraceptives. These patients were followed-up but were not part of the per protocol Population (58,303 patients).
Participants by arm
| Arm | Count |
|---|---|
| DRSP/EE Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol | 16,534 |
| OC-LNG Users of oral contraceptives containing levonorgestrel | 15,428 |
| OC-other Users of oral contraceptives containing other progestogens | 26,341 |
| Total | 58,303 |
Baseline characteristics
| Characteristic | DRSP/EE | OC-LNG | OC-other | Total |
|---|---|---|---|---|
| Age, Continuous | 25.9 years STANDARD_DEVIATION 8.1 | 25.1 years STANDARD_DEVIATION 8.7 | 24.8 years STANDARD_DEVIATION 7.8 | 25.2 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment Europe | 16534 participants | 15428 participants | 26341 participants | 58303 participants |
| Sex: Female, Male Female | 16534 Participants | 15428 Participants | 26341 Participants | 58303 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 |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 16,534 | 0 / 15,428 | 0 / 26,341 |
| serious Total, serious adverse events | 1,912 / 16,534 | 2,121 / 15,428 | 3,936 / 26,341 |
Outcome results
Primary
Arterial Thromboembolism
Arterial thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens.
Time frame: Within 10 years
Population: The number of participants refers to the ITT study population. During the course od the study, women could for example stop use of oral contraception at any point of time. Therefore, the woman-years of exposure for each group are provided in addition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DRSP/EE | Arterial Thromboembolism | 7 participants |
| OC-LNG | Arterial Thromboembolism | 22 participants |
| OC-other | Arterial Thromboembolism | 34 participants |
Comparison: Tested null hypotheses: the ATE hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.95% CI: [0.2, 0.9]
Comparison: Tested null hypotheses: the ATE hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.95% CI: [0.2, 0.9]
Primary
Breast Cancer
Breast cancer associated with the use of hormonal contraceptives either containing both drospirenone (DRSP) and ethinylestradiol (EE), levonorgestrel (LNG) or any other hormonal contraceptive without DRSP.
Time frame: Within 10 years
Population: The number of participants refers to the ITT study population. During the course od the study, women could for example stop use of oral contraception at any point of time. Therefore, the woman-years of exposure for each group are provided in addition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DRSP/EE | Breast Cancer | 27 participants |
| OC-LNG | Breast Cancer | 31 participants |
| OC-other | Breast Cancer | 45 participants |
Comparison: Tested null hypotheses: the breast cancer hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.95% CI: [0.5, 1.4]
Comparison: Tested null hypotheses: the breast cancer hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.95% CI: [0.6, 1.5]
Primary
Venous Thromboembolism
Venous thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens.
Time frame: Within 10 years
Population: The number of participants refers to the ITT study population. During the course od the study, women could for example stop use of oral contraception at any point of time. Therefore, the woman-years of exposure for each group are provided in addition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DRSP/EE | Venous Thromboembolism | 56 participants |
| OC-LNG | Venous Thromboembolism | 53 participants |
| OC-other | Venous Thromboembolism | 144 participants |
Comparison: Tested null hypotheses: the VTE hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.95% CI: [0.8, 1.7]
Comparison: Tested null hypotheses: the VTE hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.95% CI: [0.5, 1]