Safety of the Etonogestrel-releasing Implant During the Puerperium of Healthy Women

Study Overview
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Brief Summary
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The purpose of this study to assess the safety of the etonogestrel-releasing subdermal implant (Implanon) inserted during the immediate puerperium of healthy women.

Detailed Description
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Many contraceptive methods are currently available. However, about 50% of all pregnancies in the world are not planned, most of them occurring in developing countries. Long-lasting reversible contraceptives such as the etonogestrel implant represent an option for the reduction of unwanted pregnancies, especially among patients at risk for a short intergestational period. In addition to preventing an undesired pregnancy, these methods have an impact on the reduction of the maternal-fetal morbidity-mortality known to be associated with these short intervals, also minimizing the malnutrition and the cycle of poverty caused by multiparity. On the basis of inclusion and exclusion criteria, we will selected 40 puerperae aged 18 to 35 years at the Low Risk Prenatal Care Program of the University Hospital of Ribeirão Preto, University of São Paulo (HC-FMRP). The subjects will be randomized to two types of treatment (etonogestrel-releasing implant to be inserted 24 to 48 hours after delivery or 150 mg medroxyprogesterone administered every three months starting 6 weeks after delivery). Blood samples (40 mL) will be collected in a single procedure from these patients and stored for later determination of multiple hemostatic and metabolic variables at 24-48 hours and at 6 and 12 weeks after delivery. Data on maternal and neonatal clinical parameter will be also collected.

Official Title
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Safety of the Etonogestrel-releasing Implant During the Puerperium of Healthy Women

Conditions
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Breastfeeding, Contraception

Intervention / Treatment
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* Drug: etonogestrel implant
* Drug: depot medroxyprogesterone acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 18 and 35 years Postpartum contraception desire Exclusion Criteria: smoking, alcoholism or drug addiction presence of systemic diseases (diabetis melittus, cardiovascular disease, autoimmune diseases, liver disease, thyroid disease, or congenital renal hyperplasia) having a body mass index ≥ 30 kg/m2 personal history of arterial or venous thrombosis using any medication that might interfere with blood coagulation or with the assessment of haemostatic and inflammatory variables presenting alterations in hepatic enzymes being allergic to local anaesthetics (xylocaine)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: etonogestrel implant<br>Etonogestrel releasing contraceptive implant (Implanon®, NV Organon, Oss, The Netherlands) inserted 24-48 h after delivery. It is compounded by 68mg of etonogestrel, 3years of duration. | Drug: etonogestrel implant<br>* Etonogestrel-releasing subdermal implant (Implanon) inserted during the immediate postpartum period (from 24 to 48 hours postpartum)<br>* Other names: Implanon, Etonogestrel implant;|
| Active Comparator: depot medroxyprogesterone acetate<br>At the 6th week postpartum, this group received intramuscular 150 mg of depot medroxyprogesterone acetate (Contracept®, EMS Sigma Pharma, Hortolandia, Brazil). | Drug: depot medroxyprogesterone acetate<br>* 150 mg medroxyprogesterone administered I.M. every three months starting 6 weeks after delivery<br>* Other names: medroxyprogesterone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Etonogestrel-releasing Contraceptive Subdermal Implant Inserted During the Immediate Puerperium Effects on the Hemostatic System of Healthy Women Over a Period of Twelve Weeks | Activated protein C (APC) resistance is the most important marker of coagulation system in women using hormonal contraceptive methods. APC resistance was determined by testing the effect of APC on the endogenous thrombin potential (ETP) using the Calibrated Automated Thrombogram® (CAT) assay. The sensitivity ratio or APC (APCsr) of each plasma sample was determined in the presence or absence of approximately 4 nM APC (Enzyme Research Laboratories, Swansea, United Kingdom). The APC concentration was adjusted to maintain the residual thrombin generation activity in normal pooled plasma at approximately 10%. Normal pooled plasma was run in parallel on each plate. The normalized ratio (nAPCsr) was determined by dividing the APCsr of an individual sample by the APCsr of the pooled plasma. Thus, nAPCsr >1.0 indicated APC resistance. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal (Clinical and Metabolic) and Neonatal (Clinical) Safety Regarding the Use of the Etonogestrel Implant During the Immediate Postpartum Period and the First 12 Weeks Postpartum | Evaluation during the immediate postpartum period was performed at the hospital 24-48 h after delivery, in the morning and after a 12-h fast. Women and newborns were both weighed (Kg), and the blood pressure (mmHg), waist circumference (WC) (cm) and height (m) of the women were each measured by the same observer. Peripheral blood samples (20 mL) were collected and processed within 2 h after being collected. After clotting the serum, samples were centrifuged at room temperature for 10 min, and the sera were stored at -80°C until they were used for the simultaneous determination of all variables except for the complete blood count, which was performed before clotting. The following variables were analyzed: fasting serum glucose; total cholesterol (TC), high density lipoprotein (HDL) cholesterol, and triglycerides (TG), and low density lipoprotein (LDL) cholesterol | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adverse Effects, Etonogestrel, Postpartum period, Contraception, Hemostasis, Metabolism