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Trial record 72 of 100 for:    DROSPIRENONE AND ETHINYL ESTRADIOL

International Active Surveillance Study of Women Taking Oral Contraceptives (INAS-OC)

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ClinicalTrials.gov Identifier: NCT00335257
Recruitment Status : Completed
First Posted : June 9, 2006
Results First Posted : November 18, 2014
Last Update Posted : November 18, 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
Condition Contraception
Enrollment 85109
Recruitment Details Overall, 91,474 patients were recruited for the INAS-OC study. Of these, 6,365 participants were excluded due to protocol violations.
Pre-assignment Details  
Arm/Group Title OC DRSP-24d OC DRSP-21d OCs Non-DRSP
Hide Arm/Group Description OCs containing DRSP (Yaz®, 24 day regimen) OCs containing DRSP (Yasmin®, 21 day regimen) Users of OCs containing other progestins
Period Title: Overall Study
Started 15542 9377 60190
Completed 15542 [1] 9377 60190 [1]
Not Completed 0 0 0
[1]
Numbers completed refer to first follow-up. Individual follow-up ranged between 0.5 and 6.0 years.
Arm/Group Title OC DRSP-24d OC DRSP-21d OCs Non-DRSP Total
Hide Arm/Group Description OCs containing DRSP (Yaz®, 24 day regimen ) OCs containing DRSP (Yasmin®, 21 day regimen) Users of OCs containing other progestins Total of all reporting groups
Overall Number of Baseline Participants 15542 9377 60190 85109
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15542 participants 9377 participants 60190 participants 85109 participants
<=18 years
2054
  13.2%
1149
  12.3%
7582
  12.6%
10785
  12.7%
Between 18 and 65 years
13488
  86.8%
8227
  87.7%
52608
  87.4%
74323
  87.3%
>=65 years
0
   0.0%
1
   0.0%
0
   0.0%
1
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15542 participants 9377 participants 60190 participants 85109 participants
26.21  (7.64) 26.14  (7.48) 26.34  (7.73) 26.29  (7.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15542 participants 9377 participants 60190 participants 85109 participants
Female
15542
 100.0%
9377
 100.0%
60190
 100.0%
85109
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15542 participants 9377 participants 60190 participants 85109 participants
Germany 922 1438 11207 13567
United States 10299 3978 37892 52169
Austria 738 611 2945 4294
Croatia 509 68 371 948
Italy 1644 1427 2657 5728
Poland 1169 1457 3664 6290
Sweden 261 398 1454 2113
1.Primary Outcome
Title Venous Thromboembolism (VTE); Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Study participants that were not excluded due to protocol violation
Arm/Group Title OC DRSP-24d OC DRSP-21d OCs Non-DRSP NOHC No Use
Hide Arm/Group Description:
24-day regimen of DRSP/EE
21-day regimen of DRSP/EE
Users of OCs containing other progestins than DRSP
Non-oral hormonal contraception (injections, implants, levonorgestrel-containing IUDs, or contraceptive patches)
No (hormonal) contraception at last contact
Overall Number of Participants Analyzed 7264 5605 39316 4070 28854
Measure Type: Number
Unit of Measure: participants
19 16 101 7 19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OC DRSP-24d, OCs Non-DRSP
Comments Tested null hypotheses: the VTE hazard ratio for DRSP(24d) vs. Non-DRSP is higher or equal to 2
Type of Statistical Test Non-Inferiority or Equivalence
Comments Sample size calculations were based on a non-inferiority test of two exponential survival curves.These calculations are based on the following assumptions: 1) one-sided α 0.025; 2) power (1-β) of 0.90; 3) VTE incidence rate of 9/10.000 WY and 4) non-inferiority limit hazard ratio of 2. Furthermore, a study of this size would exclude a threefold risk of ATE.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
0.5 to 1.3
Estimation Comments Hazard ratio was adjusted for age, BMI, duration of current use, family history of VTE
2.Primary Outcome
Title Arterial Thromboembolism (ATE), Hazard Ratio for DRSP-24 Day vs. Non-DRSP OCs
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Study participants that were not excluded due to protocol violation
Arm/Group Title OC DRSP-24d OC DRSP-21d OCs Non-DRSP NOHC No Use
Hide Arm/Group Description:
24-day regimen of DRSP/EE
21-day regimen of DRSP/EE
Users of OCs containing other progestins
Non-oral hormonal contraception (injections, implants, levonorgestrel-containing IUDs, or contraceptive patches)
No (hormonal) contraception
Overall Number of Participants Analyzed 7264 5605 39316 4070 28854
Measure Type: Number
Unit of Measure: participants
Total number of ATE 4 3 30 2 7
of which acute myocardial infarction 2 0 10 1 3
of which ichemic stroke 1 3 15 0 2
of which transient ischemic attack (TIA) 1 0 3 0 2
of which peripheral ATE 0 0 2 1 0
Time Frame Information on adverse events was collected over a time period of 5 years.
Adverse Event Reporting Description Complete cohorts, as-treated population. All study participants were asked for adverse events at each follow-up. The total number of serious adverse events do not include 132 SAEs (due to data entry options), for which information on organ system is missing.
 
Arm/Group Title DRSP-24d DRSP-21d OCs Non-DRSP NOHC No Use
Hide Arm/Group Description 24-day regimen of DRSP/EE 21-day regimen of DRSP/EE Users of OCs containing other progestins Non-oral hormonal contraception (injections, implants, levonorgestrel-containing IUDs, or patches) No (hormonal) contraception)
All-Cause Mortality
DRSP-24d DRSP-21d OCs Non-DRSP NOHC No Use
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
DRSP-24d DRSP-21d OCs Non-DRSP NOHC No Use
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   583/7264 (8.03%)   499/5605 (8.90%)   2740/39316 (6.97%)   254/4070 (6.24%)   1756/28854 (6.09%) 
Blood and lymphatic system disorders           
Diseases of the blood and blood-forming organs  1  4/7264 (0.06%)  5/5605 (0.09%)  12/39316 (0.03%)  3/4070 (0.07%)  15/28854 (0.05%) 
Cardiac disorders           
Cardiovascular system  1  41/7264 (0.56%)  51/5605 (0.91%)  278/39316 (0.71%)  29/4070 (0.71%)  98/28854 (0.34%) 
Ear and labyrinth disorders           
Ear  1  3/7264 (0.04%)  7/5605 (0.12%)  9/39316 (0.02%)  1/4070 (0.02%)  6/28854 (0.02%) 
Endocrine disorders           
Endocrine diseases  1  12/7264 (0.17%)  8/5605 (0.14%)  47/39316 (0.12%)  5/4070 (0.12%)  26/28854 (0.09%) 
Eye disorders           
Eye  1  1/7264 (0.01%)  2/5605 (0.04%)  14/39316 (0.04%)  0/4070 (0.00%)  7/28854 (0.02%) 
Gastrointestinal disorders           
Digestive system  1  145/7264 (2.00%)  116/5605 (2.07%)  553/39316 (1.41%)  56/4070 (1.38%)  259/28854 (0.90%) 
Infections and infestations           
Infectious diseases  1  37/7264 (0.51%)  32/5605 (0.57%)  137/39316 (0.35%)  14/4070 (0.34%)  68/28854 (0.24%) 
Injury, poisoning and procedural complications           
Injury, poisoning, accidents, etc  1  85/7264 (1.17%)  66/5605 (1.18%)  383/39316 (0.97%)  33/4070 (0.81%)  136/28854 (0.47%) 
Musculoskeletal and connective tissue disorders           
Musculoskeletal system and connective tissue  1  12/7264 (0.17%)  15/5605 (0.27%)  81/39316 (0.21%)  9/4070 (0.22%)  48/28854 (0.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Neoplasms, malignant  1  26/7264 (0.36%)  14/5605 (0.25%)  119/39316 (0.30%)  7/4070 (0.17%)  57/28854 (0.20%) 
Neoplasms, benign  1  6/7264 (0.08%)  5/5605 (0.09%)  36/39316 (0.09%)  1/4070 (0.02%)  14/28854 (0.05%) 
Pregnancy, puerperium and perinatal conditions           
Pregnancy, delivery and puerperium  1 [1]  22/7264 (0.30%)  32/5605 (0.57%)  151/39316 (0.38%)  9/4070 (0.22%)  571/28854 (1.98%) 
Psychiatric disorders           
Psychiatric and neurological disorders  1  53/7264 (0.73%)  32/5605 (0.57%)  226/39316 (0.57%)  23/4070 (0.57%)  109/28854 (0.38%) 
Reproductive system and breast disorders           
Genitourinary system  1  93/7264 (1.28%)  74/5605 (1.32%)  471/39316 (1.20%)  44/4070 (1.08%)  253/28854 (0.88%) 
Respiratory, thoracic and mediastinal disorders           
Respiratory system  1  39/7264 (0.54%)  30/5605 (0.54%)  183/39316 (0.47%)  18/4070 (0.44%)  77/28854 (0.27%) 
Skin and subcutaneous tissue disorders           
Skin  1  4/7264 (0.06%)  10/5605 (0.18%)  40/39316 (0.10%)  2/4070 (0.05%)  12/28854 (0.04%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, ICD-10
[1]
SAEs, which occurred within 3 months after stop of hormonal contraceptive use, were attributed to the last OC/NOHC used by the women. Therefore, pregnancy related SAEs in OC/NOHC cohorts do not reflect unwanted pregnancies during OC/NOHC use.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DRSP-24d DRSP-21d OCs Non-DRSP NOHC No Use
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7264 (0.00%)   0/5605 (0.00%)   0/39316 (0.00%)   0/4070 (0.00%)   0/28854 (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
Name/Title: Juergen Dinger, MD, PhD
Organization: Center for Epidemiology and Health Research, Germany
Phone: 0049(0)30 945 10120
Responsible Party: Juergen Dinger, MD, PhD, Center for Epidemiology and Health Research, Germany
ClinicalTrials.gov Identifier: NCT00335257     History of Changes
Other Study ID Numbers: ZEG 2005-2
First Submitted: June 8, 2006
First Posted: June 9, 2006
Results First Submitted: November 6, 2014
Results First Posted: November 18, 2014
Last Update Posted: November 18, 2014