Clinical trial NCT02550067: The Evidence for Contraceptive Options and HIV Outcomes Trial
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Contraception
Keywords: HIV infection
DepoLevonorgestrel
Contraception
DMPA
Copper IUD
Levonorgestrel implant
IUD
Lead sponsor: FHI 360
Sponsor class: OTHER
Collaborators: name: University of Washington
name: Wits Reproductive Health and HIV Institute
name: World Health Organization
name: Madibeng Centre for Research
name: Maternal Adolescent and Child Health Research
name: Qhakaza Mbokodo Research Clinic
name: The Aurum Institute NPC
name: Effective Care Research Unit
name: Emavundleni Research Centre
name: Setshaba Research Centre
name: University of North Carolina, Chapel Hill
name: Family Life Association of Swaziland
name: ICAP Columbia University
name: Kenya Medical Research Institute
First posted: 2015-09-15
Enrollment: 7830
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Compare risks of HIV acquisition between women randomized to DMPA, LNG and copper IUD
timeFrame: From enrollment to 18 months
Secondary outcomes:
measure: Compare pregnancy rates among women randomized to DMPA, LNG and copper IUD
timeFrame: From enrollment to 18 months
measure: Compare rates of adverse events that lead to discontinuation among women randomized to DMPA, LNG and copper IUD
timeFrame: From enrollment to 18 months
measure: Compare contraceptive continuation rates among women randomized to DMPA, LNG and copper IUD
timeFrame: From enrollment to 18 months
measure: Compare SAEs among women randomized to DMPA, LNG and copper IUD
timeFrame: From enrollment to 18 months
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kisumu East Research Care and Training Program
city: Brits
country: South Africa
facility: Madibeng Centre for Research
city: Cape Town
country: South Africa
facility: Emavundleni Research Centre
city: Durban
country: South Africa
facility: MatCH Research Unit Commercial City
city: East London
country: South Africa
facility: Effective Care Research Unit (ECRU) Frere Maternity Hospital
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute (WRHI)
city: Klerksdorp
country: South Africa
facility: Aurum Klerksdorp Gavin Churchyard Legacy Centre
city: Ladysmith
country: South Africa
facility: QM ladysmith
city: Pietermaritzburg
country: South Africa
facility: MatCH Research Unit Edendale
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre
city: Manzini
country: Swaziland
facility: FLAS/ICAP Clinic 1& Clinic 2
city: Lusaka
country: Zambia
facility: University Teaching Hospital, Lusaka, Zambia
Study officials:
References:
citation: Beesham I, Mansoor LE, Joseph Davey DL, Palanee-Phillips T, Smit J, Ahmed K, Selepe P, Louw C, Singata-Madliki M, Kotze P, Heffron R, Parikh UM, Wiesner L, Rees H, Baeten JM, Beksinska M. Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial. J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):26-30. doi: 10.1097/QAI.0000000000003023. Epub 2022 Jun 9.
citation: Ryan R, Mussa A, Singtaa-Madliki M, Batting J, Balakrishna Y, Morroni C, Hofmeyr GJ. Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial. Front Glob Womens Health. 2022 May 20;3:887541. doi: 10.3389/fgwh.2022.887541. eCollection 2022.
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citation: Beksinska M, Issema R, Beesham I, Lalbahadur T, Thomas K, Morrison C, Hofmeyr GJ, Steyn PS, Mugo N, Palanee-Phillips T, Ahmed K, Nair G, Baeten JM, Smit J. Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021 Apr 6;34:100800. doi: 10.1016/j.eclinm.2021.100800. eCollection 2021 Apr.
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