The Evidence for Contraceptive Options and HIV Outcomes Trial

NCT ID: NCT02550067

Last Updated: 2019-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

7830 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-14

Study Completion Date

2018-10-31

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.

Conditions

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HIV Contraception

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Depot medroxyprogesterone acetate (DMPA)

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.

Group Type ACTIVE_COMPARATOR

DMPA

Intervention Type DRUG

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.

Levonorgestrel implant (LNG)

Women randomized to implants will receive LNG implants in the arm, at enrolment from trained clinicians.

Group Type ACTIVE_COMPARATOR

LNG

Intervention Type DRUG

Women randomized to implants will receive LNG implants in the arm, at enrolment from trained clinicians.

Copper T380a IUD

Women randomized to IUDs will receive their IUDs at enrolment. Trained providers will insert T380a copper IUDs using standard insertion techniques.

Group Type ACTIVE_COMPARATOR

Copper IUD

Intervention Type DRUG

Women randomized to IUDs will receive their IUDs at enrolment. Trained providers will insert T380a copper IUDs using standard insertion techniques.

Interventions

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DMPA

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.

Intervention Type DRUG

LNG

Women randomized to implants will receive LNG implants in the arm, at enrolment from trained clinicians.

Intervention Type DRUG

Copper IUD

Women randomized to IUDs will receive their IUDs at enrolment. Trained providers will insert T380a copper IUDs using standard insertion techniques.

Intervention Type DRUG

Other Intervention Names

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Depot medroxyprogesterone acetate Levonorgestrel implant Copper T380a IUD

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.
Minimum Eligible Age

16 Years

Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Washington

OTHER

Sponsor Role collaborator

Wits Reproductive Health and HIV Institute

OTHER

Sponsor Role collaborator

World Health Organization

OTHER

Sponsor Role collaborator

Madibeng Centre for Research

OTHER

Sponsor Role collaborator

Maternal Adolescent and Child Health Research

UNKNOWN

Sponsor Role collaborator

Qhakaza Mbokodo Research Clinic

UNKNOWN

Sponsor Role collaborator

The Aurum Institute NPC

OTHER

Sponsor Role collaborator

Effective Care Research Unit

OTHER

Sponsor Role collaborator

Emavundleni Research Centre

UNKNOWN

Sponsor Role collaborator

Setshaba Research Centre

UNKNOWN

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role collaborator

Family Life Association of Swaziland

UNKNOWN

Sponsor Role collaborator

ICAP Columbia University

UNKNOWN

Sponsor Role collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role collaborator

FHI 360

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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FLAS/ICAP Clinic 1& Clinic 2

Manzini, , Eswatini

Site Status

Kisumu East Research Care and Training Program

Kisumu, , Kenya

Site Status

Madibeng Centre for Research

Brits, , South Africa

Site Status

Emavundleni Research Centre

Cape Town, , South Africa

Site Status

MatCH Research Unit Commercial City

Durban, , South Africa

Site Status

Effective Care Research Unit (ECRU) Frere Maternity Hospital

East London, , South Africa

Site Status

Wits Reproductive Health and HIV Institute (WRHI)

Johannesburg, , South Africa

Site Status

Aurum Klerksdorp Gavin Churchyard Legacy Centre

Klerksdorp, , South Africa

Site Status

QM ladysmith

Ladysmith, , South Africa

Site Status

MatCH Research Unit Edendale

Pietermaritzburg, , South Africa

Site Status

Setshaba Research Centre

Soshanguve, , South Africa

Site Status

University Teaching Hospital, Lusaka, Zambia

Lusaka, , Zambia

Site Status

Countries

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Eswatini Kenya South Africa Zambia

References

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Morrison S, Batting J, Wanga V, Beesham I, Deese J, Hofmeyr GJ, Kasaro MP, Louw C, Morrison C, Mugo NR, Palanee-Phillips T, Pleaner M, Reddy K, Scoville CW, Smit J, Stringer JSA, Ahmed K, Bukusi E, Kotze P, Baeten JM; ECHO Trial Team. True and False Positive HIV Point of Care Test Results in a Prospective Multinational Study of At-Risk African Women: Implications for Large-Scale Repeat HIV Testing in HIV Prevention Programs. J Acquir Immune Defic Syndr. 2024 Dec 1;97(4):364-370. doi: 10.1097/QAI.0000000000003497.

Reference Type DERIVED
PMID: 39085989 (View on PubMed)

Hofmeyr GJ, Singata-Madliki M, Batting J, Balakrishna Y, Morroni C. Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial. BMC Womens Health. 2024 Mar 8;24(1):167. doi: 10.1186/s12905-024-02990-8.

Reference Type DERIVED
PMID: 38459552 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35972853 (View on PubMed)

Bunjun R, Ramla TF, Jaumdally SZ, Noel-Romas L, Ayele H, Brown BP, Gamieldien H, Harryparsad R, Dabee S, Nair G, Onono M, Palanee-Phillips T, Scoville CW, Heller KB, Baeten JM, Bosinger SE, Burgener A, Passmore JS, Jaspan H, Heffron R. Initiating Intramuscular Depot Medroxyprogesterone Acetate Increases Frequencies of Th17-like Human Immunodeficiency Virus Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial. Clin Infect Dis. 2022 Nov 30;75(11):2000-2011. doi: 10.1093/cid/ciac284.

Reference Type DERIVED
PMID: 35941737 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35669313 (View on PubMed)

Palanee-Phillips T, Rees HV, Heller KB, Ahmed K, Batting J, Beesham I, Heffron R, Justman J, Makkan H, Mastro TD, Morrison SA, Mugo N, Nair G, Kiarie J, Philip NM, Pleaner M, Reddy K, Selepe P, Steyn PS, Scoville CW, Smit J, Thomas KK, Donnell D, Baeten JM; ECHO Trial Consortium. High HIV incidence among young women in South Africa: Data from a large prospective study. PLoS One. 2022 Jun 3;17(6):e0269317. doi: 10.1371/journal.pone.0269317. eCollection 2022.

Reference Type DERIVED
PMID: 35657948 (View on PubMed)

Tanko RF, Bunjun R, Dabee S, Jaumdally SZ, Onono M, Nair G, Palanee-Phillips T, Harryparsad R, Happel AU, Gamieldien H, Qumbelo Y, Sinkala M, Scoville CW, Heller K, Baeten JM, Bosinger SE, Burgener A, Heffron R, Jaspan HB, Passmore JAS. The Effect of Contraception on Genital Cytokines in Women Randomized to Copper Intrauterine Device, Depot Medroxyprogesterone Acetate, or Levonorgestrel Implant. J Infect Dis. 2022 Sep 13;226(5):907-919. doi: 10.1093/infdis/jiac084.

Reference Type DERIVED
PMID: 35263421 (View on PubMed)

Mugo NR, Stalter RM, Heffron R, Rees H, Scoville CW, Morrison C, Kourtis AP, Bukusi E, Beksinka M, Philip NM, Beesham I, Deese J, Edward V, Donnell D, Baeten JM; Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium. Incidence of Herpes Simplex Virus Type 2 Infection Among African Women Using Depot Medroxyprogesterone Acetate, a Copper Intrauterine Device, or a Levonorgestrel Implant for Contraception: A Nested Randomized Trial. Clin Infect Dis. 2022 Sep 10;75(4):586-595. doi: 10.1093/cid/ciab1027.

Reference Type DERIVED
PMID: 34910143 (View on PubMed)

Donnell D, Beesham I, Welch JD, Heffron R, Pleaner M, Kidoguchi L, Palanee-Phillips T, Ahmed K, Baron D, Bukusi EA, Louw C, Mastro TD, Smit J, Batting JR, Malahleha M, Bailey VC, Beksinska M, Rees H, Baeten JM; ECHO Trial Consortium. Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study. Lancet HIV. 2021 Aug;8(8):e495-e501. doi: 10.1016/S2352-3018(21)00048-5. Epub 2021 Jun 11.

Reference Type DERIVED
PMID: 34126052 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33898953 (View on PubMed)

Beesham I, Welch JD, Heffron R, Pleaner M, Kidoguchi L, Palanee-Phillips T, Ahmed K, Baron D, Bukusi EA, Louw C, Mastro TD, Smit J, Batting JR, Malahleha M, Bailey VC, Beksinska M, Donnell D, Baeten JM; ECHO Trial Consortium. Integrating oral PrEP delivery among African women in a large HIV endpoint-driven clinical trial. J Int AIDS Soc. 2020 May;23(5):e25491. doi: 10.1002/jia2.25491.

Reference Type DERIVED
PMID: 32396700 (View on PubMed)

Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. Lancet. 2019 Jul 27;394(10195):303-313. doi: 10.1016/S0140-6736(19)31288-7. Epub 2019 Jun 13.

Reference Type DERIVED
PMID: 31204114 (View on PubMed)

Other Identifiers

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523201

Identifier Type: -

Identifier Source: org_study_id

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