Comparison of Two IUDs Among Cape Town HIV-positive Women

Study Overview
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Brief Summary
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This study will inform international medical guidelines as to whether the Levonorgestrel intrauterine device (LNG IUD), a highly effective long-acting reversible contraceptive method, is safe and acceptable as compared to the copper intrauterine device (C-IUD) for HIV-positive women in Cape Town, South Africa. If the LNG IUD is found to be safe and acceptable, the introduction of this method to HIV positive women in developing countries could significantly reduce unplanned pregnancy and mother-to-child transmission of HIV, and confer non-contraceptive benefits to HIV-positive women in Sub-Saharan Africa.

Detailed Description
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Design: Single site, double-blind, randomized controlled trial Population: HIV-positive South African women between the ages of 18 and 40 years Study size: At least 166 women Study intervention: Levonorgestrel intrauterine device (LNG IUD) or the copper T-380 intrauterine device (C-IUD) Duration & Follow-up: Approximately 48 months in total. Recruitment will take approximately 24 months. After enrollment, each participant will be followed for 24 months. Primary Objectives: To compare LNG IUD safety to the safety of the C-IUD with respect to genital HIV shedding, a surrogate for potential for HIV transmission, overall and in the presence and absence of ART. Secondary Objectives: 1) To compare LNG IUD safety to the safety of the C-IUD with respect to HIV progression as measured by changes in plasma viral load (VL) at 6 months between the two pre-ART study arms. 2) To explore LNG IUD safety with respect to non-HIV related outcomes, including hemoglobin change, incidence of sexually-transmitted infections (STIs) and pelvic inflammatory disease (PID). 3) To measure LNG IUD acceptability through device continuation and other measures for the LNG IUD as compared to the C-IUD. 4) To compare three genital tract sampling methods to determine which provides optimal recovery of HIV RNA and immune mediators over a series of three visits. Primary Endpoints: Change in detection and quantity of HIV RNA genital VL measures between study arms at baseline and 6 months, and over 24 months following IUD insertion. Secondary Endpoints: 1) Measures of HIV disease progression, including CD4 change, time to ART initiation, and mean plasma VL change from baseline to 6 and through 24 months among pre-ART women. 2) Hemoglobin change and incidence of STIs and PID for all participants through 24 months. 3) IUD continuation and expulsion rates between study arms comparing different IUDs over a 24-month period and acceptability measures through quantitative and qualitative methods. 4) Comparison of female genital tract sampling methods for recovery of HIV RNA as measured by VL and immune mediators (e.g. cytokines). Study Site: Gugulethu Community Health Centre (GCHC), Cape Town, South Africa

Official Title
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Comparison of Two IUDs Among Cape Town HIV-positive Women: A Randomized Controlled Trial Assessing Safety of Registered Products in South Africa

Conditions
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HIV

Intervention / Treatment
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* Device: Mirena levonorgestrel IUD
* Device: Copper T-380a IUD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Willing and able to provide written informed consent (IC) to be screened for and to participate in the trial Interested and willing to use the IUD as a family planning method. Between 18 to 40 years of age (inclusive): This age range includes women during their years of greatest fertility and 18 is the age of majority for research consent in South Africa. Willing to participate in all aspects of the study and to comply with study procedures and visits, for 24 months, including: Be randomized Adhere to follow-up schedule and willing to be contacted by site staff between study visits (by phone and/or in person) Provide contact/locator information Agree for site staff to review clinic chart to confirm HIV status Has documented HIV infection For pre-ART entrants: ART-ineligible at screening, based on current South African ART guidelines Be at least 6 months post-delivery and not pregnant or desiring pregnancy for the next 30 months. For ART-using entrants: ART-use demonstrated by clinical records reflecting laboratory measures consistent with ART use and evidence of viral suppression (plasma VL<1000 copies/mL) at the most recent VL measure. Be at least 6 weeks post-delivery and not pregnant or desiring pregnancy for the next 30 months. Intending residence in Cape Town area for next 30 months No documented or known history of infertility or sterilization No gross evidence of cervical neoplasia on examination No prior history of ectopic pregnancy No history of or suspected hormonally-dependent neoplasm or undiagnosed abnormal vaginal bleeding Local language fluency and comprehension Not participating in any other clinical trial with a biomedical intervention Have no condition that, based on the opinion of the Site PI, would preclude provision of informed consent, make participation in the study unsafe, or complicate interpretation of data.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Copper T-380a IUD<br>Copper T-380a IUD | Device: Copper T-380a IUD<br>* intrauterine contraception system<br>|
| Active Comparator: Mirena Levonorgestrel IUD<br>Mirena levonorgestrel IUD | Device: Mirena levonorgestrel IUD<br>* Intrauterine contraception system<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare LNG IUD safety to the safety of the C-IUD with respect to genital HIV shedding, a surrogate for potential for HIV transmission, overall and in the presence and absence of ART. |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare LNG IUD safety to the safety of the C-IUD with respect to HIV progression as measured by changes in plasma viral load (VL) at 6 months between the two pre-ART study arms. |  | 24 months | 
| Explore LNG IUD safety with respect to non-HIV related outcomes, including hemoglobin change, incidence of sexually-transmitted infections (STIs) and pelvic inflammatory disease (PID). |  | 24 months | 
| Measure LNG IUD acceptability through device continuation and other measures for the LNG IUD as compared to the C-IUD. |  | 24 months | 
| Compare three genital tract sampling methods to determine which provides optimal recovery of HIV RNA and immune mediators over a series of three visits. |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AE adverse event, AIDS acquired immunodeficiency syndrome, ALT (SGPT) alanine aminotransferase, ART antiretroviral therapy, AST (SGOT) aspartate aminotransferase, DCF data collection forms, DMC Data Monitoring Committee, FDA (U.S.) Food and Drug Administration, GCP Good Clinical Practice guidelines, HB sAg Hepatitis B surface antigen, ICH International Council for Harmonization, IND Investigational New Drug Application, IRB Institutional Review Board, IU International units, mg milligram(s), mm3 cubic millimeter(s), PCR polymerase chain reaction, SAE serious adverse event, µg microgram, ULN upper limit of the normal range, WB Western Blot