Contraceptive UsageNCT03336346
Effect of Dolutegravir on Etonogestrel Levels in HIV-infected Women in Botswana
An observational study of Contraceptive Usage and HIV Infections, run by Columbia University at 1 site in Botswana.
Trial summary
The primary aim is to assess if etonogestrel (ENG) implant users taking dolutegravir (DTG) have a 20% or greater change in their ENG plasma levels, compared to women taking no antiretroviral therapy (ART). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraceptive Usage, HIV Infections, Drug Interaction
- What is being tested?
- dolutegravir, ENG implant and Efavirenz
- Type of treatment
- Medical device
- How many people
- 148 participants
- Where
- 1 siteBotswana
- Study dates
- 15 Nov 2017to 11 Dec 2019
- Phase
- Observational
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Reproductive-aged HIV-infected women using dolutegravir and using single-rod, etonogestrel-releasing subdermal implant. Reproductive-aged HIV-infected women using efavirenz and using single-rod, etonogestrel-releasing subdermal implant. Reproductive-aged HIV-unifected women using single-rod, etonogestrel-releasing subdermal implant.
Who may be able to join
- Etonogestrel implant as their sole method of hormonal contraception
- Etonogestrel implant in-situ for three to twelve months.
- Dolutegravir (DTG) use for at least 60 days (Using DTG-based ART-regimen if applicable)
- Efavirenz (EFV) use for at least 60 days (Using EFV-based ART-regimen if applicable)
Who cannot join
- Exclude women using concomitant enzyme-inducing drugs, including rifampicin for tuberculosis treatment and anti-convulsant medications (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Dolutegravir-based ART on Plasma Etonogestrel Levels in HIV-infected Women Using Contraceptive Implants in Botswana
The primary aim is to assess if etonogestrel (ENG) implant users taking dolutegravir (DTG) have a 20% or greater change in their ENG plasma levels, compared to women taking no antiretroviral therapy (ART). A secondary aim is to assess whether ENG implant users taking dolutegravir have significantly higher ENG plasma levels than ENG implant users taking efavirenz.
This is a cross-sectional, non-randomized evaluation to compare ENG levels between 3 and 12 months post-implant insertion in three groups of women: 1) women using DTG-based ART (n=90), 2) women using EFV-based ART (n=90), and 3) women using no ART (not HIV infected) (n=90). This study will be conducted in Botswana in Southern Africa among women using the ENG implant, and involves a one-time collection of blood and questionnaire.
Read the detailed description
Efavirenz-based antiretroviral therapy is effective in treating HIV and had become standard in the World Health Organization (WHO) guidelines. However, despite its effectiveness in lowering viral load, there is also solid evidence that it decreases the effectiveness of etonogestrel-releasing implants. This presents a difficult clinical scenario in countries where the HIV burden is significant in reproductive age women.
Following the SINGLE trial, dolutegravir has replaced efavirenz in many settings as first-line ART. In 2016, Botswana became the first country in Africa to adopt this as a guideline, however, the effect that dolutegravir has on hormonal contraceptives has not been widely studied. This project seeks to understand the interaction between etonogestrel levels in HIV-infected women who are using dolutegravir-based ART by directly measuring etonogestrel blood levels using liquid chromatography-mass spectrometry in HIV-negative and HIV-infected women using contraceptive implants.
Because the implant is fairly new in Botswana, most participants will have had implants inserted 3-12 months prior to study. An HIV-infected, non-ART, comparison group is no longer permissible, practically or ethically, as countries across Africa, including Botswana, are moving to HIV "Test and Treat." This means that ART initiation is now occurring at time of HIV-diagnosis regardless of cluster of differentiation 4 (CD4) count or disease stage; therefore, in this study, the comparison group will be HIV-uninfected implant users. This comparison will answer the key question of whether the ENG implant when used simultaneously with DTG provides plasma ENG levels comparable to a group in which it has established contraceptive efficacy (i.e. HIV-uninfected, healthy women of reproductive age).
- Conditions
- Contraceptive Usage, HIV Infections, Drug Interaction
- Being tested
- dolutegravir, ENG implant, Efavirenz
- Keywords
- DTG, Dolutegravir, Efavirenz, Etonogestrel
- Medical subject headings
- Contraception Behavior, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dolutegravirDrug
Also called Tivicay, DTG
HIV integrase strand transfer inhibitor used in combination ART
ENG implantDevice
Also called Nexplanon ®, Implanon NXT ®, single-rod, etonogestrel-releasing, subdermal implant
Reversible contraception implant
EfavirenzDrug
Also called Sustiva, EFV
non-nucleoside reverse transcriptase inhibitor used in combination ART
| Study group | Role | What they receive |
|---|---|---|
| DTG group | Reproductive-aged HIV-infected women taking dolutegravir-based ART and using single-rod, etonogestrel-releasing, subdermal implant (ENG implant) Receives: Drug: dolutegravir; Device: ENG implant | |
| No ART group | Reproductive-aged HIV-uninfected women using single-rod, etonogestrel-releasing, subdermal implant (ENG implant) Receives: Device: ENG implant | |
| EFV group | Reproductive-aged HIV-infected women taking efavirenz-based ART and using single-rod, etonogestrel-releasing, subdermal implant (ENG implant) Receives: Device: ENG implant; Drug: Efavirenz |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference (percentage) in ENG plasma levels in the DTG group compared to no ART group
Difference between the DTG group and no ART group
Measured: Up to 12 months after implant
Secondary outcomes (1)
Difference (percentage) in ENG plasma levels in the DTG group compared to EFV group
Difference between the DTG group and EFV group
Measured: Up to 12 months after implant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2017
- Study start15 Nov 2017
- Primary completion30 Oct 2019
- Study completion11 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Contraceptive UsageStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carolyn Westhoff, Columbia University
- Investigators
- Carolyn L Westhoff, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03336346
- Sponsor's protocol ID
- AAAQ8556
- Status last verified
- Feb 2020
- First submitted
- 6 Nov 2017
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dolutegravir-based ART on Plasma Etonogestrel Levels in HIV-infected Women Using Contraceptive Implants in Botswana
- ClinicalTrials.gov ID
- NCT03336346
- Acronym / sponsor ID
- AAAQ8556
- Conditions
- Contraceptive Usage, HIV Infections, Drug Interaction
- Keywords
- DTG, Dolutegravir, Efavirenz, Etonogestrel
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 15 Nov 2017 (actual)
- Primary completion
- 30 Oct 2019 (actual)
- Study completion
- 11 Dec 2019 (actual)
- First posted
- 8 Nov 2017 (actual)
- 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 primary aim is to assess if etonogestrel (ENG) implant users taking dolutegravir (DTG) have a 20% or greater change in their ENG plasma levels, compared to women taking no antiretroviral therapy (ART). A secondary aim is to assess whether ENG implant users taking dolutegravir have significantly higher ENG plasma levels than ENG implant users taking efavirenz.
This is a cross-sectional, non-randomized evaluation to compare ENG levels between 3 and 12 months post-implant insertion in three groups of women: 1) women using DTG-based ART (n=90), 2) women using EFV-based ART (n=90), and 3) women using no ART (not HIV infected) (n=90). This study will be conducted in Botswana in Southern Africa among women using the ENG implant, and involves a one-time collection of blood and questionnaire.
Detailed description
Efavirenz-based antiretroviral therapy is effective in treating HIV and had become standard in the World Health Organization (WHO) guidelines. However, despite its effectiveness in lowering viral load, there is also solid evidence that it decreases the effectiveness of etonogestrel-releasing implants. This presents a difficult clinical scenario in countries where the HIV burden is significant in reproductive age women.
Following the SINGLE trial, dolutegravir has replaced efavirenz in many settings as first-line ART. In 2016, Botswana became the first country in Africa to adopt this as a guideline, however, the effect that dolutegravir has on hormonal contraceptives has not been widely studied. This project seeks to understand the interaction between etonogestrel levels in HIV-infected women who are using dolutegravir-based ART by directly measuring etonogestrel blood levels using liquid chromatography-mass spectrometry in HIV-negative and HIV-infected women using contraceptive implants.
Because the implant is fairly new in Botswana, most participants will have had implants inserted 3-12 months prior to study. An HIV-infected, non-ART, comparison group is no longer permissible, practically or ethically, as countries across Africa, including Botswana, are moving to HIV "Test and Treat." This means that ART initiation is now occurring at time of HIV-diagnosis regardless of cluster of differentiation 4 (CD4) count or disease stage; therefore, in this study, the comparison group will be HIV-uninfected implant users. This comparison will answer the key question of whether the ENG implant when used simultaneously with DTG provides plasma ENG levels comparable to a group in which it has established contraceptive efficacy (i.e. HIV-uninfected, healthy women of reproductive age).
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DTG group | – | Drug: dolutegravir, Device: ENG implantReproductive-aged HIV-infected women taking dolutegravir-based ART and using single-rod, etonogestrel-releasing, subdermal implant (ENG implant) |
| No ART group | – | Device: ENG implantReproductive-aged HIV-uninfected women using single-rod, etonogestrel-releasing, subdermal implant (ENG implant) |
| EFV group | – | Device: ENG implant, Drug: EfavirenzReproductive-aged HIV-infected women taking efavirenz-based ART and using single-rod, etonogestrel-releasing, subdermal implant (ENG implant) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Reproductive-aged HIV-infected women using dolutegravir and using single-rod, etonogestrel-releasing subdermal implant. Reproductive-aged HIV-infected women using efavirenz and using single-rod, etonogestrel-releasing subdermal implant. Reproductive-aged HIV-unifected women using single-rod, etonogestrel-releasing subdermal implant.
Key inclusion criteria (4 listed)
- Etonogestrel implant as their sole method of hormonal contraception
- Etonogestrel implant in-situ for three to twelve months.
- Dolutegravir (DTG) use for at least 60 days (Using DTG-based ART-regimen if applicable)
- Efavirenz (EFV) use for at least 60 days (Using EFV-based ART-regimen if applicable)
Key exclusion criteria (1 listed)
- Exclude women using concomitant enzyme-inducing drugs, including rifampicin for tuberculosis treatment and anti-convulsant medications (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine)
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 |
|---|---|---|
| dolutegravirAlso: Tivicay, DTGHIV integrase strand transfer inhibitor used in combination ART | Drug | DTG group |
| ENG implantAlso: Nexplanon ®, Implanon NXT ®, single-rod, etonogestrel-releasing, subdermal implantReversible contraception implant | Device | DTG group, EFV group, No ART group |
| EfavirenzAlso: Sustiva, EFVnon-nucleoside reverse transcriptase inhibitor used in combination ART | Drug | EFV group |
Primary outcome
Difference (percentage) in ENG plasma levels in the DTG group compared to no ART group
Time frame: Up to 12 months after implant
Difference between the DTG group and no ART group
1 secondary outcome
Difference (percentage) in ENG plasma levels in the DTG group compared to EFV group
Time frame: Up to 12 months after implant
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 5 Feb 2020.
- Individual participant dataSharing planned: Undecided
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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.
Carolyn L Westhoff, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Contraceptive Usage and HIV Infections, run by Columbia University at 1 site in Botswana.
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 4 inclusion and 1 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 5 Feb 2020. 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 Botswana. 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.
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?
Difference (percentage) in ENG plasma levels in the DTG group compared to no ART group (time frame: Up to 12 months after implant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Feb 2020.