NCT02550067

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
7,830

participants targeted

Target at P75+ for not_applicable hiv

Timeline
Completed

Started Dec 2015

Typical duration for not_applicable hiv

Geographic Reach
3 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 12, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 15, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

December 14, 2015

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2018

Completed
Last Updated

August 20, 2019

Status Verified

August 1, 2019

Enrollment Period

2.9 years

First QC Date

September 12, 2015

Last Update Submit

August 16, 2019

Conditions

HIVContraception

Keywords

HIV infectionDepoLevonorgestrelContraceptionDMPACopper IUDLevonorgestrel implantIUD

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • 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

Study Arms (3)

Depot medroxyprogesterone acetate (DMPA)

ACTIVE COMPARATOR

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

Levonorgestrel implant (LNG)

ACTIVE COMPARATOR

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

Drug: LNG

Copper T380a IUD

ACTIVE COMPARATOR

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

Drug: Copper IUD

Interventions

DMPADRUG

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.

Also known as: Depot medroxyprogesterone acetate
Depot medroxyprogesterone acetate (DMPA)
LNGDRUG

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

Also known as: Levonorgestrel implant
Levonorgestrel implant (LNG)
Copper IUDDRUG

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

Also known as: Copper T380a IUD
Copper T380a IUD

Eligibility Criteria

Age16 Years - 35 Years
Sexfemale
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

FLAS/ICAP Clinic 1& Clinic 2

Manzini, Eswatini

Location

Kisumu East Research Care and Training Program

Kisumu, Kenya

Location

Madibeng Centre for Research

Brits, South Africa

Location

Emavundleni Research Centre

Cape Town, South Africa

Location

MatCH Research Unit Commercial City

Durban, South Africa

Location

Effective Care Research Unit (ECRU) Frere Maternity Hospital

East London, 5201, South Africa

Location

Wits Reproductive Health and HIV Institute (WRHI)

Johannesburg, South Africa

Location

Aurum Klerksdorp Gavin Churchyard Legacy Centre

Klerksdorp, 2570, South Africa

Location

QM ladysmith

Ladysmith, South Africa

Location

MatCH Research Unit Edendale

Pietermaritzburg, South Africa

Location

Setshaba Research Centre

Soshanguve, South Africa

Location

University Teaching Hospital, Lusaka, Zambia

Lusaka, Zambia

Location

Related Publications (12)

  • 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.

    PMID: 39085989DERIVED

  • 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.

    PMID: 38459552DERIVED

  • 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.

    PMID: 35972853DERIVED

  • 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.

    PMID: 35941737DERIVED

  • 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.

    PMID: 35669313DERIVED

  • 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.

    PMID: 35657948DERIVED

  • 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.

    PMID: 35263421DERIVED

  • 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.

    PMID: 34910143DERIVED

  • 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.

    PMID: 34126052DERIVED

  • 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.

    PMID: 33898953DERIVED

  • 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.

    PMID: 32396700DERIVED

  • 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.

    PMID: 31204114DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

N,N-dimethyl-4-anisidineLevonorgestrelIntrauterine Devices, Copper

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

NorgestrelNorpregnenesNorpregnanesNorsteroidsSteroidsFused-Ring CompoundsPolycyclic CompoundsIntrauterine Devices, MedicatedIntrauterine DevicesContraceptive Devices, FemaleContraceptive DevicesEquipment and Supplies

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 12, 2015

First Posted

September 15, 2015

Study Start

December 14, 2015

Primary Completion

October 31, 2018

Study Completion

October 31, 2018

Last Updated

August 20, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will share

Individual participant data that underlie the results reported in the primary analysis, after deidentification, are available beginning 3 months following article publication ending after 36 months. The study protocol is available upon publication.The statistical code is available 3 months after publication from the corresponding author. Data is available for researchers who provide a methodologically sound proposal, which will be reviewed by the ECHO Management Committee. Proposals should be directed to icrc@uw.edu; to gain access, data requestors will need to sign a data access agreement and any proposal will require approval by the ECHO Management Committee.

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
The data are available 3 months following publication of primary analysis, for 36 months.

Locations

ZA(1)ES(1)KE(1)