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Safety and Acceptability of Vaginal Rings That Protect Women From Unintended Pregnancy (Ring-Plus)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01796613
Recruitment Status : Completed
First Posted : February 22, 2013
Last Update Posted : March 11, 2015
Sponsor:
Collaborators:
Rinda Ubuzima
University of Liverpool
Information provided by (Responsible Party):
Institute of Tropical Medicine, Belgium

Tracking Information
First Submitted Date  ICMJE February 14, 2013
First Posted Date  ICMJE February 22, 2013
Last Update Posted Date March 11, 2015
Study Start Date  ICMJE June 2013
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 19, 2013)
vaginal bacterial counts [ Time Frame: 5 months ]
Changes from baseline (pre-ring use) in vaginal bacterial counts and in the absence/presence of bacterial vaginosis-related bacteria as measured with quantitative real time polymerase chain reaction (PCR).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2013)
  • Incidence of adverse and serious adverse experiences [ Time Frame: 5 months ]
    Incidence of self-reported vaginal symptoms and clinician-observed signs Incidence of bacterial vaginosis. The numbers of women prematurely withdrawing from the study or discontinuing ring use. Incidence of adverse and serious adverse experiences . The numbers of incident sexually transmitted infections (STIs) and candidiasis. Nugent scores and Ison & Hay grading of the vaginal flora.
  • Changes in phenotype of bacterial vaginosis-related bacteria [ Time Frame: 5 months ]
    Changes in phenotype of bacterial vaginosis-related bacteria, specifically:
    • Presence of dispersed forms of bacteria;
    • Presence of adhesive forms of bacteria on epithelial cells.
  • Presence or absence of a biofilm on the contraceptive vaginal rings (CVRs) [ Time Frame: 5 months ]
    Presence or absence of a biofilm on the Contraceptive Vaginal Rings (CVRs) after intermittent or continuous use:
    • Presence of biofilm visualized by crystal violet; Visualization of adherent bacteria using Fluorescence In Situ Microscopy (FISH);
    • Identification of adherent bacteria (including but not limited to Lactobacilli sp., G. vaginalis, A. vaginae).
  • Changes in inflammatory cytokines concentrations in Cervicovaginal lavage (CVLs) [ Time Frame: 5 months ]
    Changes in inflammatory cytokines concentrations in Cervicovaginal lavage (CVLs) as measured by Luminex technology. The cytokines analyzed include, but are not limited to Interleukine-1, Interleukine-6, Interleukine-8, Interleukine-10. All samples that are showing elevated cytokine levels, as well as an equal number of controls not showing elevated cytokine levels, will be tested further for the presence of proteins involved in inflammatory pathways.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Acceptability of Vaginal Rings That Protect Women From Unintended Pregnancy
Official Title  ICMJE Safety and Acceptability of Vaginal Rings That Protect Women From Unintended Pregnancy
Brief Summary

The study is a multidisciplinary research project and has two main aims:

  1. To determine the safety of a contraceptive vaginal ring (CVR) in women, with an emphasis on its effect on the vaginal microenvironment after different durations of use: the vaginal microbiome, biofilm formation on epithelial cells and rings, inflammation and immune activation in the vagina
  2. To investigate the feasibility, acceptability and adherence to vaginal ring use in Rwandan women, including attitudes towards a future multi-purpose vaginal ring for prevention of both pregnancy and sexually transmitted infections (STI).
Detailed Description
  1. An integrated study design

    This clinical study combines a clinical safety evaluation of the contraceptive vaginal ring (CVR) with social science research on acceptability and adherence of ring use in Rwandan women.

    The clinical part of the study assesses the general safety of the contraceptive ring including the effect on the vaginal microbiome, genitourinary symptoms and signs and clinical adverse events. In addition the clinical part of the study aims to understand better the possible biofilm formation and to explore the impact of the ring on the microbiome and inflammation in the vagina.

    The social science component consists of a combination of a mixed-methods research including In-depth Interviews (IDIs), Focus Group Discussions (FGDs), questionnaires, and (if funding permits) audio computer-assisted self-interviewing (ACASI).

  2. Clinical study design

This is an open label single-centre cohort study with the NuvaRing®. A total of 120 Human Immunodeficiency Virus(HIV)-negative women will be randomized to an intermittent regimen or a continuous regimen of ring use and will be followed for maximum 14 weeks, to determine general safety of the ring in the African context, and to determine differences in the vaginal microbiome and vaginal inflammation before and after use of a contraceptive vaginal ring (CVR). Qualitative research for the social science component will be performed to address the acceptability and adherence of intermittent or continuous CVR use in more depth.

Women will be randomized into two study groups: 60 intermittent users in group A and 60 continuous users in group B. Both groups will use the NuvaRing®. Women in group A (the intermittent users) will use each CVR for 3 weeks followed by one week of no ring use to allow menstruation. Women in group B (the continuous users) will use each ring for 3 weeks, with the next ring being inserted immediately after the previous one and no off period in between [4]. The total duration from enrolment to the last study visit is maximum 14 weeks. The screening process will be a maximum of 6 weeks.

As noticed above, the study will include also a social sciences component, aimed at assessing the level of acceptability and reported adherence to intermittent and continuous Contraceptive Vaginal Rings (CVRs) use in women in Rwanda; at identifying and describe the context specific attitudes and beliefs regarding family, family planning, and gendered norms; at exploring the women's beliefs and expectations regarding future potential use of a multi-purpose ring (contraception and Human Immunodeficiency Virus (HIV) prevention); and at exploring how women and men in Rwanda perceive and experience risk related to unwanted pregnancy and Human Immunodeficiency Virus (HIV). This part of the study will result in qualitative outcomes.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Condition  ICMJE Contraception
Intervention  ICMJE
  • Device: Vaginal Ring - intermittent regimen
    NuvaRing® used intermittently. Nuvaring is a contraceptive vaginal ring, manufactured by N.V. Organon (a subsidiary of Merck & Co., Inc.,), Oss, the Netherlands. It contains 11.7 mg etonogestrel and 2.7 mg ethinylestradiol. It releases etonogestrel and ethinylestradiol at an average amount of 0.120 mg and 0.015 mg, respectively per 24 hours, over a period of 3 weeks. It is approved since 2001 by most countries within the European Union, and in the United Stated by the FDA.
    Other Name: NuvaRing®: etonogestrel/ethinylestradiol
  • Device: Vaginal Ring - continuous regimen
    NuvaRing® used continuously. Nuvaring is a contraceptive vaginal ring, manufactured by N.V. Organon (a subsidiary of Merck & Co., Inc.,), Oss, the Netherlands. It contains 11.7 mg etonogestrel and 2.7 mg ethinylestradiol. It releases etonogestrel and ethinylestradiol at an average amount of 0.120 mg and 0.015 mg, respectively per 24 hours, over a period of 3 weeks. It is approved since 2001 by most countries within the European Union, and in the United Stated by the FDA.
    Other Name: NuvaRing®: etonogestrel/ethinylestradiol
Study Arms  ICMJE
  • Active Comparator: Vaginal Ring - intermittent regimen
    3 weeks ring use followed by one week of no ring use to allow menstruation
    Intervention: Device: Vaginal Ring - intermittent regimen
  • Active Comparator: Vaginal Ring - continuous regimen
    3 weeks of ring use with no off period. The next ring is immediately inserted after the previous one
    Intervention: Device: Vaginal Ring - continuous regimen
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 19, 2013)
120
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2014
Actual Primary Completion Date March 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Able and willing to give informed consent/assent, according to national guidelines
  • Female who self-reports to be sexually active (meaning at least one penetrative vaginal coital act per month for the last 3 months prior to screening)
  • Between 18 to 35 years old, inclusive
  • Currently in good physical and mental health
  • Interested in initiating hormonal contraception
  • Able and willing to participate in the study as required by the protocol, this includes willing to undergo HIV testing and use a NuvaRing®
  • HIV negative at screening as confirmed by rapid HIV testing

Exclusion Criteria:

  • Currently using a modern contraceptive method other than barrier methods
  • Use of a hormonal contraceptive method in the three months prior to the screening visit
  • Currently using antimicrobial medication
  • Pregnant on urine pregnancy test
  • History of cardiovascular disease
  • History of hysterectomy or genital tract surgery (including cervical polypectomy, dilatation and curettage, hysteroscopy, or laparoscopy) in the three months prior to the screening visit
  • History of complications with hormonal contraception or with contra indications for the use of hormonal contraceptives such as:

    • History or known predisposition for venous thrombosis
    • History of migraine with focal neurological symptoms
    • Diabetes mellitus with vascular involvement
    • History of pancreatitis or severe hepatic disease
    • Known or suspected hypersensitivity to any of the excipients of NuvaRing®
  • History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, incontinence or urge incontinence, diagnosed chronic and/or recurrent vulvovaginal candidiasis, urethral obstruction
  • Participating in other clinical studies involving investigational products
  • Currently breastfeeding
  • Currently a smoker
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Rwanda
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01796613
Other Study ID Numbers  ICMJE ITMC0313
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Institute of Tropical Medicine, Belgium
Study Sponsor  ICMJE Institute of Tropical Medicine, Belgium
Collaborators  ICMJE
  • Rinda Ubuzima
  • University of Liverpool
Investigators  ICMJE
Principal Investigator: Tania Crucitti, PhD Institute of Tropical Medicine, Belgium
PRS Account Institute of Tropical Medicine, Belgium
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP