Clinical trial NCT01721798: Comparison of Two Intrauterine Devices (IUDs) Among Cape Town HIV-positive Women
Official title: Comparison of Two Intrauterine Devices (IUDs) Among Cape Town HIV-positive Women: A Randomized Controlled Trial Assessing Safety of Registered Products in South Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: 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
Lead sponsor: FHI 360
Sponsor class: OTHER
Collaborators: name: University of Cape Town
name: City University of New York, School of Public Health
First posted: 2012-11-06
Enrollment: 199
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 antiretroviral therapy (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 ribonucleic acid (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

Eligibility criteria: 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 intrauterine device (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-antiretroviral therapy (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 viral load (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 Principal Investigator (PI), would preclude provision of informed consent, make participation in the study unsafe, or complicate interpretation of data.

Exclusion Criteria:

* Known congenital or acquired uterine anomaly including fibroids distorting the uterine cavity;
* Known acute liver disease or hepatic neoplasm;
* Known copper storage disease;
* Known hypersensitivity to any component of the levonorgestrel IUD (LNG IUD) or copper IUD (C-IUD) or latex allergy
* Pregnant or desiring pregnancy in next 24 months
* Gross cervical lesion concerning for neoplasia
* CD4 lymphocyte count\<350 cells/mm3 if not using ART
* Less than 6 weeks postpartum

Primary outcomes:
measure: Participants With Detectable Genital Tract HIV Ribonucleic Acid (RNA) Viral Load (VL)
timeFrame: Enrollment to 24 months
Secondary outcomes:
measure: Participants With Detectable Plasma HIV Ribonucleic Acid (RNA) Viral Load Among Those Using Antiretroviral Therapy (ART)
timeFrame: Enrollment to 24 months
measure: Mean Hemoglobin Concentration as Part of Intrauterine Contraceptive Safety
timeFrame: Enrollment to 24 months
measure: Participants Continuing Use of the Allocated Intrauterine Device (IUD)
timeFrame: Enrollment to 24 months
measure: HIV Ribonucleic Acid (RNA) Concentration by Lower Female Genital Tract Sampling Method
timeFrame: 6 months
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: University of Cape Town
state: Western Cape Province
Study officials:
affiliation: University of Cape Town
name: B Landon Myer, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: FHI 360
name: Catherine Todd, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Langwenya N, Todd CS, Jones HE, Hoover DR, Hu NC, Ronan A, Myer L. Risk-based screening to identify reproductive tract infection among HIV-infected women desiring use of intrauterine contraceptives. BMJ Sex Reprod Health. 2021 Apr;47(2):137-143. doi: 10.1136/bmjsrh-2019-200494. Epub 2020 Jul 1.
citation: Todd CS, Jones HE, Langwenya N, Hoover DR, Chen PL, Petro G, Myer L. Safety and continued use of the levonorgestrel intrauterine system as compared with the copper intrauterine device among women living with HIV in South Africa: A randomized controlled trial. PLoS Med. 2020 May 22;17(5):e1003110. doi: 10.1371/journal.pmed.1003110. eCollection 2020 May.