Trial Outcomes & Findings for Safety of the Etonogestrel-releasing Implant During the Puerperium of Healthy Women (NCT NCT00828542)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

40 participants

Primary outcome timeframe

12 weeks

Results posted on

2017-05-15

Participant Flow

Participant milestones

Participant milestones
Measure	Etonogestrel Implant Immediately after giving birth, women randomized to etonogestrel implant group had an Etonogestrel releasing contraceptive implant (Implanon®, NV Organon, Oss, The Netherlands) inserted 24-48 h after delivery. It is a long-acting reversible contraceptive method, compounded by 68mg of etonogestrel, 3years of duration.	Depot Medroxyprogesterone Acetate Women randomized to depot medroxyprogesterone acetate group had at the 6th week postpartum, 150 mg of depot medroxyprogesterone acetate intramuscular (Contracept®, EMS Sigma Pharma, Hortolandia, Brazil). A new injection was applied every 90 days if the patient wished to keep using the method.
Overall Study STARTED	23	23
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Etonogestrel Implant n=23 Participants Twenty women were allocated to receive the ETGreleasing contraceptive implant (Implanon®, NV Organon, Oss, The Netherlands) inserted 24-48 h after delivery	Depot Medroxyprogesterone n=23 Participants 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)	Total n=46 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	22.5 years STANDARD_DEVIATION 2.5 • n=5 Participants	22.9 years STANDARD_DEVIATION 4.4 • n=7 Participants	22.6 years STANDARD_DEVIATION 3.2 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Brazil	23 participants n=5 Participants	23 participants n=7 Participants	46 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Etonogestrel Implant n=20 Participants Twenty women were allocated to receive the ETGreleasing contraceptive implant (Implanon®, NV Organon, Oss, The Netherlands) inserted 24-48 h after delivery	Depot Medroxyprogesterone n=20 Participants 20 women received no contraceptives during the first 6 weeks after delivery, and at the 6th week, this group received IM 150 mg of depot medroxyprogesterone (Contracept®, EMS Sigma Pharma, Hortolandia, Brazil)
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	5.5 ratio Standard Deviation 1.5

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome data not reported

Adverse Events

Etonogestrel Implant

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Depot Medroxyprogesterone

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Etonogestrel Implant n=20 participants at risk Twenty women were allocated to receive the ETGreleasing contraceptive implant (Implanon®, NV Organon, Oss, The Netherlands) inserted 24-48 h after delivery	Depot Medroxyprogesterone n=20 participants at risk 20 women received no contraceptives during the first 6 weeks after delivery, and at the 6th week, this group received IM 150 mg of depot medroxyprogesterone (Contracept®, EMS Sigma Pharma, Hortolândia, Brazil)
Nervous system disorders headache	45.0% 9/20 • 1 year No patient experienced serious adverse event as hemorrhagic or thrombotic events. The most common adverse effect reported was headache during the first three months.	10.0% 2/20 • 1 year No patient experienced serious adverse event as hemorrhagic or thrombotic events. The most common adverse effect reported was headache during the first three months.

Additional Information

Dr. Milena Bastos Brito

Sao Paulo University

Phone: 551636022814

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place