The Evidence for Contraceptive Options and HIV Outcomes Trial

Study Overview
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Brief Summary
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The ECHO Study is an open-label randomized clinical trial that will compare three highly effective, reversible methods of contraception (including a non-hormonal method) to evaluate whether there is a link between use of any of these methods and increased risk of acquiring HIV infection. A randomized clinical trial among about 7,800 women in four countries, ECHO will deliver evidence to support and guide individual, policy and programmatic decisions on contraception for women at risk of acquiring HIV infection.

Detailed Description
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Approximately 7800 sexually active, HIV-negative women, 16-35 years old, seeking effective contraception, willing to be randomized to any of the study arms, and not desiring pregnancy for the duration of study participation will be randomly allocated to one of three study arms in a 1:1:1 ratio: depot medroxyprogesterone acetate (DMPA), levonorgestrel (LNG) implant, copper intrauterine device (IUD). Enrollment will require an estimated 18 months and the total duration of the clinical portion of the study is estimated to be 36 months. The primary objective is to compare the risks of HIV acquisition between women randomized to DMPA, levonorgestrel (LNG) implant, and copper IUDs. Secondary objectives are to compare: 1) pregnancy rates among women randomized to DMPA, LNG implant, and copper IUDs, 2) rates of serious adverse events among women randomized to DMPA, LNG implant, and copper IUDs, 3) rates of adverse events that lead to method discontinuation among women randomized to DMPA, LNG implant, and copper IUDs, and 4) contraceptive method continuation rates among women randomized to DMPA, LNG implant, and copper IUDs. Tertiary objectives are to evaluate: 1) whether age modifies the relationship between the three contraceptive methods and HIV acquisition, 2) whether HSV-2 status modifies the relationship between the three contraceptive methods and HIV acquisition, and 3) early HIV disease progression among sero-converters randomized to DMPA, LNG implant, and copper IUDs. Ancillary studies will assess biological mechanisms at the interface of contraceptives and markers of HIV risk.

Official Title
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A Multi Center, Open-Label, Randomised Clinical Trial Comparing HIV Incidence and Contraceptive Benefits in Women Using Depot Medroxyprogesterone Acetate (DMPA), Levonorgestrel (LNG) Implant, and Copper Intrauterine Devices (IUDs)

Conditions
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HIV, Contraception

Intervention / Treatment
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* Drug: DMPA
* Drug: LNG
* Drug: Copper IUD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 16-35 years of age (previously pregnant 16 and 17 year olds, where permissible by national regulations and local IRB approval) HIV-seronegative Wants to use effective contraception Is able and willing to provide written informed consent Agrees to be randomized to either DMPA, LNG implant, or copper IUD Agrees to use assigned method for 18 months Agrees to follow all study requirements Intends to stay in the study area for the next 18 months, and willing and able to provide adequate locator information If has had a recent third trimester birth, is at least 6 weeks postpartum Is sexually active (has had vaginal sex within the last 3 months) or was pregnant within the last 3 months Agrees not to participate in studies of drugs or vaccines or any other clinical research study while participating in this study. Exclusion Criteria: Reported medical contraindications (WHO MEC Category 3 or 4) to DMPA, LNG implant, or copper IUDs, including: recent septic abortion; suspicious unexplained vaginal bleeding; breast, cervical, uterine, or ovarian cancer; high BP or heart disease, venous thromboembolism, stroke, or diabetes; liver disease or liver tumours; use of liver enzyme inducing medications Is found to have pelvic tuberculosis or uterine fibroids with distortion of the uterine cavity on pelvic exam Has untreated mucus and purulent cervicitis on exam, untreated pelvic inflammatory disease (PID), or untreated known gonorrhea or chlamydia Has received a DMPA or NET-En injection in the last 6 months Has used an implant or an IUD in the last 6 months Is pregnant or intending to become pregnant in the next 18 months Has had a hysterectomy or sterilization Has previously participated in the study Has any condition (social or medical) which in the opinion of the investigator would make study participation unsafe or complicate data interpretation.

Ages Eligible for Study
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Minimum Age: 16 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Depot medroxyprogesterone acetate (DMPA)<br>Women randomized to DMPA, will receive an intramuscular injection of DMPA (medroxyprogesterone acetate sterile aqueous suspension 150 mg per 1 mL) at enrolment. Subsequent injections will be given every 3 months (i.e., at quarterly study visits) at the study site. | Drug: DMPA<br>* Women randomized to DMPA, will receive an intramuscular injection of DMPA (medroxyprogesterone acetate sterile aqueous suspension 150 mg per 1 mL) at enrolment. Subsequent injections will be given every 3 months (i.e., at quarterly study visits) at the study site.<br>* Other names: Depot medroxyprogesterone acetate;|
| Active Comparator: Levonorgestrel implant (LNG)<br>Women randomized to implants will receive LNG implants in the arm, at enrolment from trained clinicians. | Drug: LNG<br>* Women randomized to implants will receive LNG implants in the arm, at enrolment from trained clinicians.<br>* Other names: Levonorgestrel implant;|
| Active Comparator: Copper T380a IUD<br>Women randomized to IUDs will receive their IUDs at enrolment. Trained providers will insert T380a copper IUDs using standard insertion techniques. | Drug: Copper IUD<br>* Women randomized to IUDs will receive their IUDs at enrolment. Trained providers will insert T380a copper IUDs using standard insertion techniques.<br>* Other names: Copper T380a IUD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare risks of HIV acquisition between women randomized to DMPA, LNG and copper IUD | HIV infection as measured by documented HIV seroconversion occurring post-enrolment | From enrollment to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare pregnancy rates among women randomized to DMPA, LNG and copper IUD |  | From enrollment to 18 months | 
| Compare rates of adverse events that lead to discontinuation among women randomized to DMPA, LNG and copper IUD |  | From enrollment to 18 months | 
| Compare contraceptive continuation rates among women randomized to DMPA, LNG and copper IUD |  | From enrollment to 18 months | 
| Compare SAEs among women randomized to DMPA, LNG and copper IUD |  | From enrollment to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DMPA, HIV infection, DepoLevonorgestrel, Contraception, Copper IUD, Levonorgestrel implant, IUD