Clinical trial NCT02577913: European Active Surveillance Study Comparing Regimens of Administration in Combined Hormonal Contraception
Official title: European Active Surveillance Study Comparing Regimens of Administration in Combined Hormonal Contraception
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Contraception
Keywords: contraception
contraceptive patch
Levonorgestrel
gestodene
safety
Lead sponsor: Center for Epidemiology and Health Research, Germany
Sponsor class: OTHER
Collaborators: name: Gedeon Richter Plc.
First posted: 2015-10-16
Enrollment: 2281
Sex: FEMALE
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women using combined hormonal contraceptives

Brief summary: This study compares the risks of short- and long-term use of FC Patch Low with levonorgestrel-containing combined oral contraceptives (COC-LNG) in a study population representative of the actual users of the individual preparations. FC Patch Low is a transdermal contraceptive patch applied once a week for three consecutive weeks followed by a break of one week (21/7). One patch contains 2.1mg gestodene and 0.55mg ethinyl estradiol, which is equivalent of releasing 0.06mg gestodene and 0.013mg ethinyl estradiol per 24 hours.

Detailed description: FC Patch Low is a transdermal contraceptive patch applied once a week for three consecutive weeks followed by a break of one week (21/7). One patch contains 2.1mg gestodene and 0.55mg ethinyl estradiol, which is equivalent of releasing 0.06mg gestodene and 0.013mg ethinyl estradiol per 24 hours. The most relevant adverse clinical outcome that has been linked to the use of COCs is venous thromboembolism (VTE). Data from randomized clinical trials did not show any serious health concerns for FC Patch Low. However, the statistical power to detect rare adverse events is limited in these studies.

EURAS-CORA is a large, prospective, controlled, long-term active surveillance study to investigate the safety of FC Patch Low with regard to the outcomes of interest. This study follows the European Active Surveillance (EURAS) design methodology with some modifications due to country- and product-specific characteristics. The outcomes of interest will be validated via the attending physicians. A multi-faceted follow-up procedure will ensure a low loss to follow-up rate. This study will involve women from Europe who will be followed for up to 2 years. Data analysis will include multivariable techniques such as Cox regression.

The study has been terminated:

On 10th October, 2016 Gedeon Richter Plc initiated a recall of the FC Patch Low based on stability data provided by Bayer AG (licensor). Under certain conditions the stability tests showed out of specification results. Data from in vitro dissolution tests have shown altered dissolution profile for the gestodene component. Furthermore, visually observable quality defect of crystallization due to the progesterone component (gestodene) had been detected. The clinical relevance of the quality issue is currently not proven. Based on the company's safety database, no increase in the frequency of reported adverse events or in the number of unwanted pregnancies were observed in association with the quality issue of the patch. The Pearl Index calculated based on this post-marketing data and taking into account the possible under-reporting (Pearl Index: 0.50) is considerably lower than the Pearl Index based on the data from clinical trials (Pearl Index: 1.19).

The competent authorities were informed about the quality issue and Gedeon Richter Plc took the precautionary measure to stop marketing and commercializing the product. Wholesale partners were asked to recall the affected product batches currently on the market from pharmacies.

Study investigators were officially informed of the recall and study suspension on 17th October, 2016. The suspension of network expansion activities in Spain and France was immediate. Physician recruitment in Italy had not formally commenced at the time of the study suspension. All relevant ethics committees, including the EMA PAS register, were informed of the study suspension by 21st October, 2016. The maximum duration of contraceptive use for current FC Patch Low users is 10th October 2016 + 3months (or 10th January 2017). Therefore, all women currently enrolled in EURAS-CORA were followed up until January 2017.

On 22nd May 2019, ZEG Berlin were officially notified by Gedeon Richter Plc that FC Patch Low had been withdrawn from the European market.

Eligibility criteria: There will be no specific medical inclusion/exclusion criteria and no age restrictions

Inclusion Criteria:

* First ever user of a combined hormonal contraceptive "starter"
* User who restarts a combined hormonal contraceptive after at leat a two month break "restarter"
* Women willing to participate in an active surveillance study

Exclusion Criteria:

- Women who do not understand the major aspects of the study

Primary outcomes:
measure: Venous thromboembolism
timeFrame: 24 months
Secondary outcomes:
measure: Arterial thromboembolism
timeFrame: 24 months
measure: Application site reactions
timeFrame: 24 months
measure: Short- and long-term fertility
timeFrame: 24 months
measure: Pregnancy outcomes
timeFrame: 24 months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Berlin Center for Epidemiology and Health Research
Study officials:
affiliation: ZEG Berlin
name: Klaas Heinemann, MD PhD MBA
role: PRINCIPAL_INVESTIGATOR
References: