Expanded Contraception Health Options (Echo) 2 Study

PROPOSED STUDY

ECHO 2 - Evidence for Contraception Options and HIV Outcomes

A multi-centre, open label, randomised controlled trial: Progestin-only contraception vs copper IUD.

Proposed start date: April 2015

Proposed evidence for contraceptive options and HIV outcomes trial

Random allocation to 3 methods:

  • DMPA (Deop-Provera,  Petogen
  • Implant (Jadelle)
  • Copper IUD

Follow up for 18 months

Primary Outcome: HIV seroconversion.

 

PROTOCOL SUMMARY

Short title                         The Evidence for Contraceptive options and HIV Outcomes (ECHO) Trial

Design                               Multicentre, open-label, randomised clinical trial

Study arms                       Random allocation to one of three study arms in a 1:1:1 ratio: depot medroxyprogesterone acetate (DMPA), levonorgestrel (LNG) implant, copper intrauterine device (IUD)

Population                       Sexually active, HIV-negative women, 16-35 years old, seeking effective contraception, willing to be randomised to any of the study arms, and not desiring pregnancy for the duration of study participation

Sample size                      Approximately 7,800 women (2,600 per arm)

Follow-up                         18 months per woman or until closure of the study or study site

Study Sites                        Approximately 12 sites in Eastern and Southern Africa

Study Duration          Enrolment will require an estimated 18 months. Total duration of the study will be approximately 36 months from first enrolment.

Operations                       The study team, in coordination with the funders and the Data and Safety Monitoring Board, will define key metrics and a priori criteria for stopping the trial or individual arms for operational futility as part of trial design, including % of women willing to be randomised, accrual rate, % of women discontinuing methods post-randomisation, and % loss to follow-up.

Study Goal               To answer the public health question of the relative risks (HIV acquisition) and benefits (pregnancy prevention) of three commonly-used, effective contraceptive methods among women who desire contraception

 

Primary Objective

To compare the risks of HIV acquisition between women randomised to DMPA, levonorgestrel (LNG) implant, and copper IUDs

Secondary Objectives

  • To compare pregnancy rates among women randomised to DMPA, LNG implant, and copper IUDs
  • To compare rates of serious adverse events among women randomised to DMPA, LNG implant, and copper IUDs
  • To compare rates of adverse events that lead to method discontinuation among women randomised to DMPA, LNG implant, and copper IUDs
  • To compare contraceptive method continuation rates among women randomised to DMPA, LNG implant, and copper IUDs

Tertiary Objectives

  • To evaluate whether age modifies the hormonal contraception and HIV acquisition relationship
  • To evaluate whether HSV-2 status modifies the hormonal contraception and HIV acquisition relationship
  • To evaluate early HIV disease progression among seroconverters randomised to DMPA, LNG implant, and copper IUDs

Primary Endpoint            

  • HIV infection as measured by documented HIV seroconversion (defined by the HIV algorithm in Appendix 7) occurring post-enrolment

 Secondary Endpoints

  • Pregnancy
  • serious adverse events
  • Method-related adverse events resulting in method discontinuation
  • Method continuation

Tertiary Endpoints

  • HIV infection by baseline age sub-groups ≤24years versus > 24 years
  • HIV infection by baseline HSV-2 status
  • HIV plasma viral load and CD4 count