ContraceptionPhase 2/3Ring-PlusNCT01796613
Safety and Acceptability of Vaginal Rings That Protect Women From Unintended Pregnancy
A Phase 2/3 study testing Vaginal Ring - intermittent regimen and Vaginal Ring - continuous regimen in people with Contraception, run by Institute of Tropical Medicine, Belgium at 1 site in Rwanda.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- Vaginal Ring - intermittent regimen and Vaginal Ring - continuous regimen
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteRwanda
- Study dates
- Jun 2013to Mar 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
The study is a multidisciplinary research project and has two main aims:
- 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
- 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).
Read the detailed description
- 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).
- 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.
- Conditions
- Contraception
- Being tested
- Vaginal Ring - intermittent regimen, Vaginal Ring - continuous regimen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaginal Ring - intermittent regimenDevice
Also called NuvaRing®: etonogestrel/ethinylestradiol
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.
Vaginal Ring - continuous regimenDevice
Also called NuvaRing®: etonogestrel/ethinylestradiol
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.
| Study group | Role | What they receive |
|---|---|---|
| Vaginal Ring - intermittent regimen | Active comparator | 3 weeks ring use followed by one week of no ring use to allow menstruation Receives: Device: Vaginal Ring - intermittent regimen |
| Vaginal Ring - continuous regimen | Active comparator | 3 weeks of ring use with no off period. The next ring is immediately inserted after the previous one Receives: Device: Vaginal Ring - continuous regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
vaginal bacterial counts
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).
Measured: 5 months
Secondary outcomes (4)
Incidence of adverse and serious adverse experiences
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.
Measured: 5 months
Changes in phenotype of bacterial vaginosis-related bacteria
Changes in phenotype of bacterial vaginosis-related bacteria, specifically:
- Presence of dispersed forms of bacteria;
- Presence of adhesive forms of bacteria on epithelial cells.
Measured: 5 months
Presence or absence of a biofilm on the contraceptive vaginal rings (CVRs)
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).
Measured: 5 months
Changes in inflammatory cytokines concentrations in Cervicovaginal lavage (CVLs)
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.
Measured: 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2013 (estimated)
- Study startJun 2013
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Tropical Medicine, Belgium
- Sponsor type
- University, hospital or other
- Collaborators
- Rinda Ubuzima, Rwanda, University of Liverpool
- Responsible party
- Sponsor
- Investigators
- Tania Crucitti, PhD, Principal investigator, Institute of Tropical Medicine, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01796613
- Sponsor's protocol ID
- ITMC0313
- Acronym
- Ring-Plus
- Status last verified
- Mar 2015
- First submitted
- 14 Feb 2013
- Last updated
- 11 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hardy L, Jespers V, Abdellati S, De Baetselier I, Mwambarangwe L, Musengamana V, van de Wijgert J, Vaneechoutte M, Crucitti T. A fruitful alliance: the synergy between Atopobium vaginae and Gardnerella vaginalis in bacterial vaginosis-associated biofilm. Sex Transm Infect. 2016 Nov;92(7):487-491. doi: 10.1136/sextrans-2015-052475. Epub 2016 Mar 10.
PubMed 26965870Schurmans C, De Baetselier I, Kestelyn E, Jespers V, Delvaux T, Agaba SK, van Loen H, Menten J, van de Wijgert J, Crucitti T; RING PLUS study group. The ring plus project: safety and acceptability of vaginal rings that protect women from unintended pregnancy. BMC Public Health. 2015 Apr 10;15:348. doi: 10.1186/s12889-015-1680-y.
PubMed 25880636
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Acceptability of Vaginal Rings That Protect Women From Unintended Pregnancy
- ClinicalTrials.gov ID
- NCT01796613
- Acronym / sponsor ID
- Ring-Plus / ITMC0313
- Conditions
- Contraception
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Institute of Tropical Medicine, BelgiumUniversity, hospital or other
- Collaborators
- Rinda Ubuzima, Rwanda, University of Liverpool
- Study start
- Jun 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 22 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a multidisciplinary research project and has two main aims:
- 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
- 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
- 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).
- 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 design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vaginal Ring - intermittent regimen | Active comparator | Device: Vaginal Ring - intermittent regimen3 weeks ring use followed by one week of no ring use to allow menstruation |
| Vaginal Ring - continuous regimen | Active comparator | Device: Vaginal Ring - continuous regimen3 weeks of ring use with no off period. The next ring is immediately inserted after the previous one |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vaginal Ring - intermittent regimenAlso: NuvaRing®: etonogestrel/ethinylestradiolNuvaRing® 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. | Device | Vaginal Ring - intermittent regimen |
| Vaginal Ring - continuous regimenAlso: NuvaRing®: etonogestrel/ethinylestradiolNuvaRing® 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. | Device | Vaginal Ring - continuous regimen |
Primary outcome
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).
4 secondary outcomes
Incidence of adverse and serious adverse experiences
Time frame: 5 months
Changes in phenotype of bacterial vaginosis-related bacteria
Time frame: 5 months
Presence or absence of a biofilm on the contraceptive vaginal rings (CVRs)
Time frame: 5 months
Changes in inflammatory cytokines concentrations in Cervicovaginal lavage (CVLs)
Time frame: 5 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2015.
- Derived from this study: PubMed 26965870Hardy L, Jespers V, Abdellati S, De Baetselier I, Mwambarangwe L, Musengamana V, van de Wijgert J, Vaneechoutte M, Crucitti T. A fruitful alliance: the synergy between Atopobium vaginae and Gardnerella vaginalis in bacterial vaginosis-associated biofilm. Sex Transm Infect. 2016 Nov;92(7):487-491. doi: 10.1136/sextrans-2015-052475. Epub 2016 Mar 10.
- Derived from this study: PubMed 25880636Schurmans C, De Baetselier I, Kestelyn E, Jespers V, Delvaux T, Agaba SK, van Loen H, Menten J, van de Wijgert J, Crucitti T; RING PLUS study group. The ring plus project: safety and acceptability of vaginal rings that protect women from unintended pregnancy. BMC Public Health. 2015 Apr 10;15:348. doi: 10.1186/s12889-015-1680-y.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tania Crucitti, PhD principal investigator
Institute of Tropical Medicine, Belgium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Vaginal Ring - intermittent regimen and Vaginal Ring - continuous regimen in people with Contraception, run by Institute of Tropical Medicine, Belgium at 1 site in Rwanda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Rwanda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
vaginal bacterial counts (time frame: 5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01796613, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2015.