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Trial record 77 of 101 for:    DROSPIRENONE AND ETHINYL ESTRADIOL

Long-term Active Surveillance Study for Oral Contraceptives (LASS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00676065
Recruitment Status : Completed
First Posted : May 12, 2008
Results First Posted : November 19, 2014
Last Update Posted : November 19, 2014
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Juergen Dinger, MD, PhD, Center for Epidemiology and Health Research, Germany

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Conditions Arterial Thromboembolism
Venous Thromboembolism
Breast Cancer
Enrollment 58303
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).
Pre-assignment Details  
Arm/Group Title Yasmin OC-LNG OC-other
Hide Arm/Group Description Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol Users of oral contraceptives containing levonorgestrel Users of oral contraceptives containing other progestogens
Period Title: Overall Study
Started 16534 15428 26341
Completed 16534 15428 26341
Not Completed 0 0 0
Arm/Group Title DRSP/EE OC-LNG OC-other Total
Hide Arm/Group Description Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol Users of oral contraceptives containing levonorgestrel Users of oral contraceptives containing other progestogens Total of all reporting groups
Overall Number of Baseline Participants 16534 15428 26341 58303
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16534 participants 15428 participants 26341 participants 58303 participants
25.9  (8.1) 25.1  (8.7) 24.8  (7.8) 25.2  (8.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16534 participants 15428 participants 26341 participants 58303 participants
Female
16534
 100.0%
15428
 100.0%
26341
 100.0%
58303
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Europe Number Analyzed 16534 participants 15428 participants 26341 participants 58303 participants
16534 15428 26341 58303
[1]
Measure Description: This study was conducted in seven European countries: Austria, Belgium, Denmark, France, Germany, the Netherlands, and UK.
1.Primary Outcome
Title Arterial Thromboembolism
Hide Description Arterial thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens.
Time Frame Within 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DRSP/EE OC-LNG OC-other
Hide Arm/Group Description:
Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol
Users of oral contraceptives containing levonorgestrel
Users of oral contraceptives containing other progestogens
Overall Number of Participants Analyzed 16534 15428 26341
Overall Number of Units Analyzed
Type of Units Analyzed: Woman-years, AT-population
52278 57539 106221
Measure Type: Number
Unit of Measure: participants
7 22 34
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DRSP/EE, OC-LNG
Comments Tested null hypotheses: the ATE hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The LASS study was designed to analyse rare events (incidence rate <1 per 1,000 woman-years and ≥ 1 per 10,000 WY). 300,000 WY of observation would be sufficient to exclude a two-fold risk of rare events in users of DRSP compared to other oral contraceptives with a power (1-β) of 0.80 and an one-sided α of 0.05.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.2 to 0.9
Estimation Comments Hazard ratio was adjusted for age, BMI, smoking, hypertension and family history
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DRSP/EE, OC-other
Comments Tested null hypotheses: the ATE hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The LASS study was designed to analyse rare events (incidence rate <1 per 1,000 woman-years and ≥ 1 per 10,000 WY). 300,000 WY of observation would be sufficient to exclude a two-fold risk of rare events in users of DRSP compared to other oral contraceptives with a power (1-β) of 0.80 and an one-sided α of 0.05.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.2 to 0.9
Estimation Comments Hazard ratio was adjusted for age, BMI, smoking, hypertension and family history
2.Primary Outcome
Title Venous Thromboembolism
Hide Description Venous thromboembolism associated with the use of oral contraceptives containing drospirenone or levonorgestrel or other progestogens.
Time Frame Within 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DRSP/EE OC-LNG OC-other
Hide Arm/Group Description:
Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol
Users of oral contraceptives containing levonorgestrel
Users of oral contraceptives containing other progestogens
Overall Number of Participants Analyzed 16534 15428 26341
Overall Number of Units Analyzed
Type of Units Analyzed: Woman-years, AT population
52278 57539 106221
Measure Type: Number
Unit of Measure: participants
56 53 144
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DRSP/EE, OC-LNG
Comments Tested null hypotheses: the VTE hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The LASS study was designed to analyse rare events (incidence rate <1 per 1,000 woman-years and ≥ 1 per 10,000 WY). 300,000 WY of observation would be sufficient to exclude a two-fold risk of rare events in users of DRSP compared to other oral contraceptives with a power (1-β) of 0.80 and an one-sided α of 0.05.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.8 to 1.7
Estimation Comments Hazard ratio was adjusted for age, BMI, current duration of use, and family history of VTE.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DRSP/EE, OC-other
Comments Tested null hypotheses: the VTE hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The LASS study was designed to analyse rare events (incidence rate <1 per 1,000 woman-years and ≥ 1 per 10,000 WY). 300,000 WY of observation would be sufficient to exclude a two-fold risk of rare events in users of DRSP compared to other oral contraceptives with a power (1-β) of 0.80 and an one-sided α of 0.05.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
0.5 to 1.0
Estimation Comments Hazard ratio was adjusted for age, BMI, current duration of use, and family history of VTE.
3.Primary Outcome
Title Breast Cancer
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title DRSP/EE OC-LNG OC-other
Hide Arm/Group Description:
Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol
Users of oral contraceptives containing levonorgestrel
Users of oral contraceptives containing other progestogens
Overall Number of Participants Analyzed 16534 15428 26341
Overall Number of Units Analyzed
Type of Units Analyzed: Woman-years
52278 57539 106221
Measure Type: Number
Unit of Measure: participants
27 31 45
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DRSP/EE, OC-LNG
Comments Tested null hypotheses: the breast cancer hazard ratio for DRSP/E2 vs. OCs containing LNG is higher or equal to 2.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The LASS study was designed to analyse rare events (incidence rate <1 per 1,000 woman-years and ≥ 1 per 10,000 WY). 300,000 WY of observation would be sufficient to exclude a two-fold risk of rare events in users of DRSP compared to other oral contraceptives with a power (1-β) of 0.80 and an one-sided α of 0.05.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
0.5 to 1.4
Estimation Comments Hazard ratio was adjusted for age, BMI, smoking, educational level and age at menarche.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DRSP/EE, OC-other
Comments Tested null hypotheses: the breast cancer hazard ratio for DRSP/E2 vs. OCs containing other progestogens is higher or equal to 2.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The LASS study was designed to analyse rare events (incidence rate <1 per 1,000 woman-years and ≥ 1 per 10,000 WY). 300,000 WY of observation would be sufficient to exclude a two-fold risk of rare events in users of DRSP compared to other oral contraceptives with a power (1-β) of 0.80 and an one-sided α of 0.05.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.6 to 1.5
Estimation Comments Hazard ratio was adjusted for age, BMI, smoking, educational level and age at menarche.
Time Frame Information on adverse events was collected over a time period of 10 years.
Adverse Event Reporting Description ITT population. All study participants were asked for adverse events at each follow-up.
 
Arm/Group Title DRSP/EE OC-LNG OC-other
Hide Arm/Group Description Users of oral contraceptives containing 3 mg DRSP and 30 mcg ethinylestradiol Users of oral contraceptives containing levonorgestrel Users of oral contraceptives containing other progestogens
All-Cause Mortality
DRSP/EE OC-LNG OC-other
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DRSP/EE OC-LNG OC-other
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1912/16534 (11.56%)   2121/15428 (13.75%)   3936/26341 (14.94%) 
Blood and lymphatic system disorders       
Diseases of the blood and the bloodforming organs  1  7/16534 (0.04%)  9/15428 (0.06%)  18/26341 (0.07%) 
Cardiac disorders       
Cardiovascular system  1  198/16534 (1.20%)  226/15428 (1.46%)  425/26341 (1.61%) 
Ear and labyrinth disorders       
Ear  1  24/16534 (0.15%)  28/15428 (0.18%)  53/26341 (0.20%) 
Endocrine disorders       
Endocrine diseases  1  50/16534 (0.30%)  74/15428 (0.48%)  96/26341 (0.36%) 
Eye disorders       
Eye  1  19/16534 (0.11%)  24/15428 (0.16%)  40/26341 (0.15%) 
Gastrointestinal disorders       
Digestive system  1  248/16534 (1.50%)  265/15428 (1.72%)  503/26341 (1.91%) 
Infections and infestations       
Infectious diseases  1  86/16534 (0.52%)  86/15428 (0.56%)  171/26341 (0.65%) 
Injury, poisoning and procedural complications       
Injury, poisoning, accidents, etc.  1  337/16534 (2.04%)  358/15428 (2.32%)  651/26341 (2.47%) 
Musculoskeletal and connective tissue disorders       
Muscoskeletal system & connective tissue  1  206/16534 (1.25%)  233/15428 (1.51%)  403/26341 (1.53%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasms, malignant  1  59/16534 (0.36%)  72/15428 (0.47%)  124/26341 (0.47%) 
Neoplasms, benign  1  96/16534 (0.58%)  97/15428 (0.63%)  179/26341 (0.68%) 
Pregnancy, puerperium and perinatal conditions       
Pregnancy, delivery & puerperium  1 [1]  51/16534 (0.31%)  62/15428 (0.40%)  99/26341 (0.38%) 
Psychiatric disorders       
Psychiatric & neurological disorders  1  114/16534 (0.69%)  136/15428 (0.88%)  274/26341 (1.04%) 
Reproductive system and breast disorders       
Genitourinary system  1  279/16534 (1.69%)  290/15428 (1.88%)  572/26341 (2.17%) 
Respiratory, thoracic and mediastinal disorders       
Respiratory system  1  56/16534 (0.34%)  64/15428 (0.41%)  128/26341 (0.49%) 
Skin and subcutaneous tissue disorders       
Skin  1  82/16534 (0.50%)  97/15428 (0.63%)  200/26341 (0.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, ICD-10
[1]
SAEs that occurred within 3 months after stop of OC use, were attributed to the last hormonal contraceptive used by the women. Therefore, pregnancy related SAEs on OC cohorts do not necessarily reflect unwanted pregnancies during HC use
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DRSP/EE OC-LNG OC-other
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16534 (0.00%)   0/15428 (0.00%)   0/26341 (0.00%) 
In non-experimental studies the possibility of bias and residual confounding can never be entirely eliminated. The findings may exclude large, but not small relative risks.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Juergen Dinger, MD, PhD
Organization: Center for Epidemiology and Health Research Germany
Phone: +49 30 945 101 20
EMail: dinger@zeg-berlin.de
Layout table for additonal information
Responsible Party: Juergen Dinger, MD, PhD, Center for Epidemiology and Health Research, Germany
ClinicalTrials.gov Identifier: NCT00676065     History of Changes
Other Study ID Numbers: ZEG2006_03
First Submitted: May 8, 2008
First Posted: May 12, 2008
Results First Submitted: November 13, 2014
Results First Posted: November 19, 2014
Last Update Posted: November 19, 2014