ContraceptionPhase 4NCT04463680
Rifampin and the Contraceptive Implant
A Phase 4 study testing Rifampin 600 MG in people with Contraception and Tuberculosis, run by University of Colorado, Denver at 1 site in United States.
Trial summary
It is important for women taking rifampin to be aware if they are at greater risk of an unintended pregnancy while on the implant. An unintended pregnancy has many social, emotional, and financial impacts on women and society. 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
- Contraception, Tuberculosis
- What is being tested?
- Rifampin 600 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2020to 22 Feb 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- Healthy women, who have had an ENG implant for 12-36 months at the time of enrollment and will maintain their implant during the study without modifications.
Who cannot join
- o Women who are taking any known cytochrome P-450 3A4 enzyme inducers or inhibitors.
- Women with a known allergy or insensitivity to rifampin.
- Women with a body mass index (BMI) <18.5, as underweight women may have altered metabolism. The investigators will not have an upper BMI cut-off as studies have shown that overweight and obese women have equivalent metabolism and efficacy with the ENG contraceptive implant6,7.
- Exclusions Criteria (screening laboratory testing)
- Women with any hepatic or renal dysfunction as determined by a comprehensive metabolic panel. For purposes of this study, liver function tests will be evaluated and evidence of hepatic dysfunction will be defined as an ALT >52 or AST >39, which are beyond the reference range of normal values used by the University of Colorado clinical laboratory. Renal function will be assessed by a serum creatinine and a value >1.2 will be evidence of renal dysfunction as this is greater than the reference range used by the University of Colorado clinical laboratory.
- Women with any abnormal hematology as determined by a complete blood count. For purposes of this study, abnormal hematology will be defined as a WBC, RBC, or PLT value beyond the reference range of normal values used by the University of Colorado clinical laboratory.
- Women with abnormal coagulation factors as determined by coagulation factor tests (PT/INR, PTT). For purposes of this study, abnormal coagulation factors will be defined as any test value beyond the reference range of normal values used by the University of Colorado clinical laboratory.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: The Effect of Rifampin on Etonogestrel Concentrations in Contraceptive Implant Users
It is important for women taking rifampin to be aware if they are at greater risk of an unintended pregnancy while on the implant. An unintended pregnancy has many social, emotional, and financial impacts on women and society. Rifampin is also a Class C medication for pregnancy and could have potential negative effects on a developing fetus. Additionally, women considering rifampin for treatment of LTBI face additional risks with an unintended pregnancy, making the reliability of contraception even more important for these women. The results of this study can directly inform counseling on a national and international basis for women who use the contraceptive implant and are considering their treatment options for LTBI.
Read the detailed description
Rifampin is an antibiotic historically prescribed as part of a treatment regimen for active tuberculosis (TB) infection. Though active TB infections have become rarer over time in the US, it is estimated that up to 13 million people in the US may have latent TB infections (LTBIs), with even greater numbers of LTBIs worldwide1. In efforts to combat the persistent rate of LTBI, the US Centers for Disease Control and Prevention (CDC) released updated treatment guidelines for LTBI in 20181. This recommended treatment guideline consists of four treatment regimens, varying in duration from 3 to 9 months. The CDC recommends utilization of the shorter regimens when possible to achieve higher patient compliance and infection clear rates. The second shortest duration treatment regimen (4 months) consists of daily rifampin only1.
In addition to its antitubercular properties, rifampin is a known strong cytochrome P-450 (CYP) 3A4 enzyme inducer2. Similar to other strong CYP3A4 enzyme inducers (e.g. carbamazepine), rifampin can affect the serum concentrations of exogenous steroid hormones found in hormonal contraception2. The only published literature on the interaction between rifampin and hormonal contraception has focused on combined oral contraceptives3. Five studies that investigated the pharmacokinetics of combined oral contraceptives all found significant reductions in serum ethinyl estradiol and progestin concentrations with rifampin co-administration3. This pharmacokinetic effect is significant enough to warrant a category 3 recommendation (theoretical or proven risks usually outweigh the advantages) from the CDC Medical Eligibility Criteria (MEC) for Contraceptive Use for concomitant rifampin and combined hormonal contraceptive methods4. This pharmacokinetic effect is large enough to raise concerns for combined hormonal contraceptive method efficacy and recommendation of alternative methods. One of those alternative methods is the etonogestrel (ENG) implant (Nexplanon®), which has a category 2 recommendation in the CDC MEC for concomitant rifampin use4. However, in the clarifications for this recommendation, the CDC MEC warns that rifampin is "likely to reduce the effectiveness" of the ENG implant, with no supporting evidence provided4.
Prior work found that a strong CYP3A4 inducer (carbamazepine) caused clinically significant reductions in serum etonogestrel concentrations among contraceptive implant users5. The investigators found a median decrease in serum ENG of 61% (range 25-87) with 8/10 participants having serum ENG concentrations <90pg/mL after concomitant carbamazepine5. Though there is currently no published data on the pharmacokinetic interaction between rifampin and the ENG implant, given its similar enzyme induction properties, there is concern that the CDC MEC recommendation for rifampin and the ENG implant may underestimate the potential risk for contraceptive failure.
Given the social, financial, and healthcare costs of unintended pregnancies, it is imperative that the investigators better understand the drug-drug interaction between rifampin and the ENG implant. Especially in light of the contradictory category 2 recommendation and clarification in the CDC MEC4, more data are needed to determine if rifampin has a significant enough pharmacokinetic effect on the ENG implant to potentially cause contraceptive failure. This information would allow healthcare providers around the world the ability to provide improved counseling to patients needing treatment for LTBI in regards to both their TB treatment regimen and their concurrent contraceptive options.
Specific Aim:
- To evaluate the pharmacokinetic effect of rifampin on serum etonogestrel concentrations in contraceptive implant users at the dose of rifampin used for latent tuberculosis infection (LTBI) treatment (600mg per day)
- Exploratory Aim - to evaluate the effect of rifampin on serologic measures of ovulatory suppression (estradiol and progesterone) in contraceptive implant users
Hypothesis:
- The investigators hypothesize that rifampin will have a significant pharmacokinetic effect on participants' etonogestrel levels resulting in etonogestrel concentrations at least 35% decreased from baseline measurements.
Methods:
The investigators propose a prospective, pre and post study to evaluate the pharmacokinetic effect of rifampin on serum ENG levels in contraceptive implant users. The investigators will enroll healthy women using an ENG implant for at least 12 months and no greater than 36 months.
Participants will then begin a 2 week regimen of rifampin at 600mg per day. This dose is the recommended dose for treatment of LTBI and duration of 2 weeks will achieve steady state rifampin levels with adequate time for liver enzyme induction. All participants will then return at the end of the second week for a repeat blood draw. The investigators will again obtain serum as described above for planned measurement of serum ENG concentrations. The investigators will also obtain blood samples for repeat measurements of serum estradiol and progesterone. The investigators will also measure a serum rifampin level at the time of the second ENG blood draw to confirm compliance. Serum estradiol, serum progesterone, and serum rifampin levels will all be measured at the UCH Clinical Laboratory. At the conclusion of enrollment, all stored serum samples will be de-identified and shipped to a Merck® laboratory for serum ENG concentration measurement. Batch analysis will be performed using a liquid chromatography mass-spectrometry method that has been previously validated. Participants will serve as their own controls for this study.
All participants will be required to use either a back-up non-hormonal method of birth control or abstain from intercourse during the study and for 2 weeks after the last dose of rifampin. Rifampin has a half-life of 3-4 hours, and thus, will be eliminated within 1-2 days of the last dose, but the investigators will allow a full 2 weeks of buffer to ensure that the contraceptive effect of the implant has reinitiated before recommending resuming unprotected intercourse.
All study visits will occur at the Comprehensive Women's Health Clinic in Lowry.
- Conditions
- Contraception, Tuberculosis
- Being tested
- Rifampin 600 MG
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifampin 600 MGDrug
Administered daily for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Will receive 2 week regimen of rifampin 600mg per day Receives: Drug: Rifampin 600 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Etonogestrel Concentrations
Blood drawn before and after rifampin administration (2 weeks) for serum extraction and etonogestrel analysis
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start23 Sep 2020
- Primary completion22 Feb 2022
- Study completion22 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04463680
- Sponsor's protocol ID
- 19-2829
- Status last verified
- May 2023
- First submitted
- 6 Jul 2020
- Last updated
- 16 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Rifampin on Etonogestrel Concentrations in Contraceptive Implant Users
- ClinicalTrials.gov ID
- NCT04463680
- Acronym / sponsor ID
- 19-2829
- Conditions
- Contraception, Tuberculosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 23 Sep 2020 (actual)
- Primary completion
- 22 Feb 2022 (actual)
- Study completion
- 22 Feb 2022 (actual)
- First posted
- 9 Jul 2020 (actual)
- Results
- Posted 9 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It is important for women taking rifampin to be aware if they are at greater risk of an unintended pregnancy while on the implant. An unintended pregnancy has many social, emotional, and financial impacts on women and society. Rifampin is also a Class C medication for pregnancy and could have potential negative effects on a developing fetus. Additionally, women considering rifampin for treatment of LTBI face additional risks with an unintended pregnancy, making the reliability of contraception even more important for these women. The results of this study can directly inform counseling on a national and international basis for women who use the contraceptive implant and are considering their treatment options for LTBI.
Detailed description
Rifampin is an antibiotic historically prescribed as part of a treatment regimen for active tuberculosis (TB) infection. Though active TB infections have become rarer over time in the US, it is estimated that up to 13 million people in the US may have latent TB infections (LTBIs), with even greater numbers of LTBIs worldwide1. In efforts to combat the persistent rate of LTBI, the US Centers for Disease Control and Prevention (CDC) released updated treatment guidelines for LTBI in 20181. This recommended treatment guideline consists of four treatment regimens, varying in duration from 3 to 9 months. The CDC recommends utilization of the shorter regimens when possible to achieve higher patient compliance and infection clear rates. The second shortest duration treatment regimen (4 months) consists of daily rifampin only1.
In addition to its antitubercular properties, rifampin is a known strong cytochrome P-450 (CYP) 3A4 enzyme inducer2. Similar to other strong CYP3A4 enzyme inducers (e.g. carbamazepine), rifampin can affect the serum concentrations of exogenous steroid hormones found in hormonal contraception2. The only published literature on the interaction between rifampin and hormonal contraception has focused on combined oral contraceptives3. Five studies that investigated the pharmacokinetics of combined oral contraceptives all found significant reductions in serum ethinyl estradiol and progestin concentrations with rifampin co-administration3. This pharmacokinetic effect is significant enough to warrant a category 3 recommendation (theoretical or proven risks usually outweigh the advantages) from the CDC Medical Eligibility Criteria (MEC) for Contraceptive Use for concomitant rifampin and combined hormonal contraceptive methods4. This pharmacokinetic effect is large enough to raise concerns for combined hormonal contraceptive method efficacy and recommendation of alternative methods. One of those alternative methods is the etonogestrel (ENG) implant (Nexplanon®), which has a category 2 recommendation in the CDC MEC for concomitant rifampin use4. However, in the clarifications for this recommendation, the CDC MEC warns that rifampin is "likely to reduce the effectiveness" of the ENG implant, with no supporting evidence provided4.
Prior work found that a strong CYP3A4 inducer (carbamazepine) caused clinically significant reductions in serum etonogestrel concentrations among contraceptive implant users5. The investigators found a median decrease in serum ENG of 61% (range 25-87) with 8/10 participants having serum ENG concentrations <90pg/mL after concomitant carbamazepine5. Though there is currently no published data on the pharmacokinetic interaction between rifampin and the ENG implant, given its similar enzyme induction properties, there is concern that the CDC MEC recommendation for rifampin and the ENG implant may underestimate the potential risk for contraceptive failure.
Given the social, financial, and healthcare costs of unintended pregnancies, it is imperative that the investigators better understand the drug-drug interaction between rifampin and the ENG implant. Especially in light of the contradictory category 2 recommendation and clarification in the CDC MEC4, more data are needed to determine if rifampin has a significant enough pharmacokinetic effect on the ENG implant to potentially cause contraceptive failure. This information would allow healthcare providers around the world the ability to provide improved counseling to patients needing treatment for LTBI in regards to both their TB treatment regimen and their concurrent contraceptive options.
Specific Aim:
- To evaluate the pharmacokinetic effect of rifampin on serum etonogestrel concentrations in contraceptive implant users at the dose of rifampin used for latent tuberculosis infection (LTBI) treatment (600mg per day)
- Exploratory Aim - to evaluate the effect of rifampin on serologic measures of ovulatory suppression (estradiol and progesterone) in contraceptive implant users
Hypothesis:
- The investigators hypothesize that rifampin will have a significant pharmacokinetic effect on participants' etonogestrel levels resulting in etonogestrel concentrations at least 35% decreased from baseline measurements.
Methods:
The investigators propose a prospective, pre and post study to evaluate the pharmacokinetic effect of rifampin on serum ENG levels in contraceptive implant users. The investigators will enroll healthy women using an ENG implant for at least 12 months and no greater than 36 months.
Participants will then begin a 2 week regimen of rifampin at 600mg per day. This dose is the recommended dose for treatment of LTBI and duration of 2 weeks will achieve steady state rifampin levels with adequate time for liver enzyme induction. All participants will then return at the end of the second week for a repeat blood draw. The investigators will again obtain serum as described above for planned measurement of serum ENG concentrations. The investigators will also obtain blood samples for repeat measurements of serum estradiol and progesterone. The investigators will also measure a serum rifampin level at the time of the second ENG blood draw to confirm compliance. Serum estradiol, serum progesterone, and serum rifampin levels will all be measured at the UCH Clinical Laboratory. At the conclusion of enrollment, all stored serum samples will be de-identified and shipped to a Merck® laboratory for serum ENG concentration measurement. Batch analysis will be performed using a liquid chromatography mass-spectrometry method that has been previously validated. Participants will serve as their own controls for this study.
All participants will be required to use either a back-up non-hormonal method of birth control or abstain from intercourse during the study and for 2 weeks after the last dose of rifampin. Rifampin has a half-life of 3-4 hours, and thus, will be eliminated within 1-2 days of the last dose, but the investigators will allow a full 2 weeks of buffer to ensure that the contraceptive effect of the implant has reinitiated before recommending resuming unprotected intercourse.
All study visits will occur at the Comprehensive Women's Health Clinic in Lowry.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Rifampin 600 MGWill receive 2 week regimen of rifampin 600mg per day |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy women, who have had an ENG implant for 12-36 months at the time of enrollment and will maintain their implant during the study without modifications.
Key exclusion criteria (7 listed)
- o Women who are taking any known cytochrome P-450 3A4 enzyme inducers or inhibitors.
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 |
|---|---|---|
| Rifampin 600 MGAdministered daily for 2 weeks | Drug | Intervention |
Primary outcome
Serum Etonogestrel Concentrations
Time frame: 2 weeks
Blood drawn before and after rifampin administration (2 weeks) for serum extraction and etonogestrel analysis
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Contraception
Enrolling by invitation
Flo Digital Contraceptive Study
Contraception Use
Recruiting
Estimating the Impact of Sexuality Education and Mobile Health Services on Reproductive Health and Empowerment Among Adolescents in Sierra Leone for the Family Planning Impact Lab
Reproductive Health, Sexual Health
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingObservational study
FLOW: Influence of the Menstrual Cycle on Alcohol Use in Women
Alcohol Use, Alcohol Consumption
Not yet recruiting
Impact of Gender-Transformative Interventions on Contraceptive Use and Reproductive Autonomy in Somalia
Contraceptive Behavior, Social Norms
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rifampin 600 MG in people with Contraception and Tuberculosis, run by University of Colorado, Denver at 1 site in United States.
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 1 inclusion and 7 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 16 May 2023. 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 United States. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Serum Etonogestrel Concentrations (time frame: 2 weeks). 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 16 May 2023.