Breastfeeding, Contraception
Conditions
Keywords
Adverse Effects, Etonogestrel, Postpartum period, Contraception, Hemostasis, Metabolism
Brief summary
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
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.
Interventions
Etonogestrel-releasing subdermal implant (Implanon) inserted during the immediate postpartum period (from 24 to 48 hours postpartum)
150 mg medroxyprogesterone administered I.M. every three months starting 6 weeks after delivery
Sponsors
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Etonogestrel-releasing Contraceptive Subdermal Implant Inserted During the Immediate Puerperium Effects on the Hemostatic System of Healthy Women Over a Period of Twelve Weeks | 12 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 12 weeks | 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 |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Etonogestrel Implant Twenty women were allocated to receive the ETGreleasing contraceptive implant (Implanon®, NV Organon, Oss, The Netherlands) inserted 24-48 h after delivery | 23 |
| Depot Medroxyprogesterone 20 women received no contraceptives during the first 6 weeks after delivery, and at the 6th week, this group received IM 150 mg of DMPA (Contracept®, EMS Sigma Pharma, Hortolândia, Brazil) | 23 |
| Total | 46 |
Baseline characteristics
| Characteristic | Depot Medroxyprogesterone | Etonogestrel Implant | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 23 Participants | 46 Participants |
| Age, Continuous | 22.9 years STANDARD_DEVIATION 4.4 | 22.5 years STANDARD_DEVIATION 2.5 | 22.6 years STANDARD_DEVIATION 3.2 |
| Region of Enrollment Brazil | 23 participants | 23 participants | 46 participants |
| Sex: Female, Male Female | 23 Participants | 23 Participants | 46 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 20 | 2 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etonogestrel Implant | Etonogestrel-releasing Contraceptive Subdermal Implant Inserted During the Immediate Puerperium Effects on the Hemostatic System of Healthy Women Over a Period of Twelve Weeks | 5.9 ratio | Standard Deviation 1.8 |
| Depot Medroxyprogesterone | Etonogestrel-releasing Contraceptive Subdermal Implant Inserted During the Immediate Puerperium Effects on the Hemostatic System of Healthy Women Over a Period of Twelve Weeks | 5.5 ratio | Standard Deviation 1.5 |
Secondary
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
Time frame: 12 weeks