Ignite Creation Date:
2024-05-06 @ 7:28 PM
Last Modification Date:
2024-10-26 @ 3:07 PM
Study NCT ID:
NCT06028555
Status:
RECRUITING
Last Update Posted:
2023-09-08
First Post:
2023-07-04
Brief Title:
International Active Surveillance Study Native Estrogen Estetrol E4 Safety Study
Sponsor:
Center for Epidemiology and Health Research Germany
Organization:
Center for Epidemiology and Health Research Germany
Study Overview
Official Title:
International Active Surveillance Study Native Estrogen Estetrol E4 Safety Study
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
INAS-NEES
Brief Summary:
Multinational comparative prospective active surveillance study that follows two cohorts
The primary objective of the study is to characterize and compare the risks of E4Drospirenone DRSP with levonorgestrel-containing combined oral contraceptives EELNG in a study population that is representative of the actual users of these preparations The main clinical outcome of interest is venous thromboembolism VTE specifically deep venous thrombosis DVT and pulmonary embolism PE Secondary objectives include measuring the occurrence of unintended pregnancy assessing the risk of arterial thromboembolism ATE describing the drug utilization pattern describing the baseline risk profile for VTE and ATE and investigating outcomes associated with foetal exposure to E4DRSP
The primary objective of the study is to characterize and compare the risks of E4Drospirenone DRSP with levonorgestrel-containing combined oral contraceptives EELNG in a study population that is representative of the actual users of these preparations The main clinical outcome of interest is venous thromboembolism VTE specifically deep venous thrombosis DVT and pulmonary embolism PE Secondary objectives include measuring the occurrence of unintended pregnancy assessing the risk of arterial thromboembolism ATE describing the drug utilization pattern describing the baseline risk profile for VTE and ATE and investigating outcomes associated with foetal exposure to E4DRSP
Detailed Description:
Rationale and background
The combined oral contraceptive COC containing estetrol E4 and drospirenone DRSP E4DRSP is a novel oral contraceptive containing a fixed dose of E4 142 mg and DRSP 3 mg E4 is a natural oestrogen only produced during pregnancy by the foetal liver When combined with the progestin DRSP ovulation is inhibited The E4DRSP combination may have less impact on hepatic and haemostasis parameters in comparison to combinations of ethinyl estradiol EE and levonorgestrel LNG or EE and DRSP Yet it is unknown whether this regimen has an impact on the cardiovascular risk associated with the use of hormonal contraceptives
Study design
Multinational comparative prospective active surveillance study that follows two cohorts The cohorts consist of new users starters and restarters of two different groups of hormonal contraceptives E4DRSP and EELNG The study is taking a non-interventional approach to provide comprehensive information on these treatments in a routine clinical practice setting Study participants will be enrolled via an international network of COC-prescribing health care professionals HCPs and then followed up for one to two years All outcomes of interest will be captured by direct contact with the study participants Reported outcomes of interest will be validated via attending physicians and relevant source documents The classification of outcomes of interest into confirmed and not confirmed will be verified by blinded independent adjudication
Population
Approximately 101000 study participants 50500 E4DRSP and 50500 EELNG new users will be recruited via a network of COC-prescribing health care professionals in Europe the USA and Brazil All new users starters and restarters prescribed E4DRSP or EELNG who are willing to participate may be eligible for enrolment in the study
Data sources
This is a field study that entails exposure to COCs and the occurrence of clinical outcomes of interest by completing questionnaires at baseline study entry and follow-up at 6- 12- 18- and 24-months post-baseline in addition to potential confounding factors and potential effect modifiers Medical confirmation of the occurrence of a clinical outcome of interest will be sought from the attending HCP andor study participant eg diagnostic report discharge letter
Study size
The study is sufficiently powered to show non-inferiority of E4DRSP compared to EELNG assuming that the VTE risk among E4DRSP users is not higher than among EELNG users For this purpose a total of 101000 women 50500 E4DRSP users and 50500 EELNG users will be recruited and followed up taking into account treatment adherence treatment stoppingswitching and lost to follow-up LTFUdropout
Data analysis
The final analyses will include both an as-treated AT and an intention-to-treat ITT analysis All eligible women will be assigned to the ITT and AT population at baseline Only women with follow-up information will be considered for longitudinal analysis Women who never started their prescribed baseline medication will be considered in the ITT analysis but excluded from the AT analysis Population characteristics eg socio-economic factors parameters of reproductive contraceptive history and medical history will be summarized descriptively and used to estimate the probability of treatment differences Inverse probability of treatment weighting combined with time-to-event analysis of VTE will be carried out based on the extended Cox model to calculate hazard ratios HR with 95 confidence intervals The null hypothesis to be tested is HR of VTE 15 ie the VTE HR for E4DRSP vs EELNG is higher than or equal to 15 The alternative hypothesis is HR of VTE 15
The combined oral contraceptive COC containing estetrol E4 and drospirenone DRSP E4DRSP is a novel oral contraceptive containing a fixed dose of E4 142 mg and DRSP 3 mg E4 is a natural oestrogen only produced during pregnancy by the foetal liver When combined with the progestin DRSP ovulation is inhibited The E4DRSP combination may have less impact on hepatic and haemostasis parameters in comparison to combinations of ethinyl estradiol EE and levonorgestrel LNG or EE and DRSP Yet it is unknown whether this regimen has an impact on the cardiovascular risk associated with the use of hormonal contraceptives
Study design
Multinational comparative prospective active surveillance study that follows two cohorts The cohorts consist of new users starters and restarters of two different groups of hormonal contraceptives E4DRSP and EELNG The study is taking a non-interventional approach to provide comprehensive information on these treatments in a routine clinical practice setting Study participants will be enrolled via an international network of COC-prescribing health care professionals HCPs and then followed up for one to two years All outcomes of interest will be captured by direct contact with the study participants Reported outcomes of interest will be validated via attending physicians and relevant source documents The classification of outcomes of interest into confirmed and not confirmed will be verified by blinded independent adjudication
Population
Approximately 101000 study participants 50500 E4DRSP and 50500 EELNG new users will be recruited via a network of COC-prescribing health care professionals in Europe the USA and Brazil All new users starters and restarters prescribed E4DRSP or EELNG who are willing to participate may be eligible for enrolment in the study
Data sources
This is a field study that entails exposure to COCs and the occurrence of clinical outcomes of interest by completing questionnaires at baseline study entry and follow-up at 6- 12- 18- and 24-months post-baseline in addition to potential confounding factors and potential effect modifiers Medical confirmation of the occurrence of a clinical outcome of interest will be sought from the attending HCP andor study participant eg diagnostic report discharge letter
Study size
The study is sufficiently powered to show non-inferiority of E4DRSP compared to EELNG assuming that the VTE risk among E4DRSP users is not higher than among EELNG users For this purpose a total of 101000 women 50500 E4DRSP users and 50500 EELNG users will be recruited and followed up taking into account treatment adherence treatment stoppingswitching and lost to follow-up LTFUdropout
Data analysis
The final analyses will include both an as-treated AT and an intention-to-treat ITT analysis All eligible women will be assigned to the ITT and AT population at baseline Only women with follow-up information will be considered for longitudinal analysis Women who never started their prescribed baseline medication will be considered in the ITT analysis but excluded from the AT analysis Population characteristics eg socio-economic factors parameters of reproductive contraceptive history and medical history will be summarized descriptively and used to estimate the probability of treatment differences Inverse probability of treatment weighting combined with time-to-event analysis of VTE will be carried out based on the extended Cox model to calculate hazard ratios HR with 95 confidence intervals The null hypothesis to be tested is HR of VTE 15 ie the VTE HR for E4DRSP vs EELNG is higher than or equal to 15 The alternative hypothesis is HR of VTE 15
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None