PK Study of Rifampicin Interactions With DMPA and Efavirenz in TB (PRIDE-HT)
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|ClinicalTrials.gov Identifier: NCT02412436|
Recruitment Status : Completed
First Posted : April 9, 2015
Results First Posted : September 25, 2018
Last Update Posted : July 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|HIV-1 Infection Tuberculosis||Drug: Depot medroxyprogesterone acetate||Phase 2|
Globally, women comprise 52% of all people living with human immunodeficiency virus (HIV). Decisions about contraception in a population of women infected with both tuberculosis (TB) and HIV are of paramount importance. In the setting of the treatment of active TB, preventing pregnancy becomes even more important because it allows women to attain a level of health that will support healthy future pregnancies. Treatment options for TB may be limited in pregnancy because of concerns about teratogenicity. Millions of women around the world use depot medroxyprogesterone acetate (DMPA, trade name Depo-Provera) for prevention of pregnancy. DMPA is an intermediate-acting progesterone-only injectable contraceptive with a high efficacy rate. Unfortunately, DMPA's safety and effectiveness among women co-infected with TB and HIV is unknown since the interactions of TB treatment, combination ART (cART), and DMPA have not been well studied. The results of this study are likely to be applicable to women receiving RIF-containing TB treatment who are not being treated concurrently with EFV as well, given that addition of EFV to RIF is unlikely to increase induction of metabolizing enzymes significantly beyond the induction achieved with RIF alone.
The study population included premenopausal women, 18 to 46 years of age, who were co-infected with HIV and TB. To be eligible to enroll in the study, participants must have been on EFV 600 mg once daily plus two or more nucleoside reverse transcriptase inhibitors (NRTIs) for at least 28 days prior to study entry with no plans to change therapy for the 12 weeks of the study. Women must have been on the continuation phase of active TB treatment (with a minimum of 12 weeks remaining) taking RIF 8-12 mg/kg orally and INH 4-6 mg/kg orally on a 5-day or more per week schedule (or as directed by national guidelines for TB treatment). At study entry/week 0, DMPA 150 mg was administered intramuscularly as a single dose.
Study duration was 12 weeks. Visits occurred at weeks 0, 2, 4, 6, 8, 10, and 12. The key evaluations included physical examination, clinical assessments, hematology, chemistry, HIV RNA, pregnancy testing, plasma progesterone levels, and plasma DMPA concentration levels.
The sample size was 46 participants, of which 42 had to be evaluable. Participants who missed two successive visits prior to week 8 and those who did not complete the week 10 and week 12 clinic visits with available DMPA concentrations and progesterone levels were not evaluable and replaced in the sample size. The final number of participants enrolled was 62 participants, with only 42 evaluable.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||62 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Non-Randomized Study of Pharmacokinetic Interactions Among Depot Medroxyprogesterone Acetate (DMPA), Rifampicin (RIF), and Efavirenz (EFV) in Women Co-infected With Human Immunodeficiency Virus (HIV) and Tuberculosis (TB)|
|Actual Study Start Date :||November 3, 2015|
|Actual Primary Completion Date :||June 15, 2017|
|Actual Study Completion Date :||June 15, 2017|
Experimental: Arm A: Depot medroxyprogesterone acetate
At study entry/week 0, participants received depot medroxyprogesterone acetate (DMPA) 150 mg administered intramuscularly as a single dose and co-administered with rifampicin (RIF) and efavirenz (EFV).
Drug: Depot medroxyprogesterone acetate
Depot medroxyprogesterone acetate intramuscular injection
Other Name: DMPA
- Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Week 12 [ Time Frame: Week 12 ]The percent of participants with plasma DMPA concentrations below 0.1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.
- Percent of Participants With Progesterone Levels Above 1 ng/mL at Week 12 [ Time Frame: Week 12 ]The percent of participants with plasma progesterone levels above 1 ng/mL was calculated with an exact Clopper-Pearson 95% confidence interval. Ovulation generally occurs when the progesterone level is > 5 ng/mL. If there were participants with plasma progesterone levels > 1 ng/mL, then the percent of participants with plasma progesterone levels > 5 ng/mL would have been calculated by study week.
- Percent of Participants With DMPA Concentrations Below 0.1 ng/mL at Weeks 2, 4, 6, 8, and 10 [ Time Frame: Weeks 2, 4, 6, 8, and 10 ]The percents of participants with plasma DMPA concentrations below 0.1 ng/mL at weeks 2, 4, 6, 8, and 10 were calculated with exact Clopper-Pearson 95% confidence intervals. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.
- Cumulative Percentage of Participants With DMPA < 0.1 ng/mL [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12 ]The cumulative percentage of participants having a DMPA concentration less than 0.1 ng/mL at week 12 was calculated using a Kaplan-Meier estimator with an associated standard error. The confidence interval was calculated using a log-log transformation. Suppression of ovulation generally occurs as long as the DMPA level is => 0.1 ng/mL.
- DMPA AUC [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12 ]Describe the DMPA plasma area under the curve (AUC) between 0 and 12 weeks, where AUC(0-12wks) was calculated using non-compartmental methods.The Week 0 time point was drawn prior to DMPA injection.
- DMPA Cmin [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12 ]Describe the DMPA minimum observed concentration (Cmin) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.
- DMPA Cmax [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12 ]Describe the DMPA maximum observed concentration (Cmax) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.
- DMPA CL/F [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12 ]Describe the apparent DMPA clearance (CL/F) between 0 and 12 weeks. The Week 0 time point was drawn prior to DMPA injection.
- Percent of Participants Who Experienced a Grade 3 or Higher Sign/Symptom or Laboratory Abnormality [ Time Frame: Weeks 2, 4, 6, 8, 10, and 12 ]The percent of participants who experienced a grade 3 (severe) or higher sign/symptom or laboratory abnormality were calculated with an exact Clopper-Pearson 95% confidence interval. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS AE Grading Table (V1.0).
- DMPA Half-life [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12 ]Describe the terminal elimination half-life of DMPA (t½) between 0 and 12 weeks, where t½ was calculated using nonlinear mixed-effects (NLME) modelling. The Week 0 time point was drawn prior to DMPA injection.
- Time at Which Participant-specific Estimated Elimination Slopes for DMPA Level Cross the Threshold of 0.1 ng/mL [ Time Frame: Weeks 0, 2, 4, 6, 8, 10, and 12 ]Describe the time at which DMPA levels drop below the threshold of 0.1 ng/mL, based on participant-specific estimated elimination slopes from nonlinear mixed-effects (NLME) models. The Week 0 time point was drawn prior to DMPA injection.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02412436
|Gaborone Prevention/Treatment Trials CRS (12701)|
|Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) CRS (31460)|
|Kisumu, Kenya, 40100|
|Durban Adult HIV CRS (11201)|
|Durban, South Africa, 4013 SF|
|Univ. of Witwatersrand CRS (11101)|
|Johannesburg, South Africa|
|UZ-Parirenyatwa CRS (30313)|
|Study Chair:||Rosie Mngqibisa, MBChB, MPH||Durban Adult HIV CRS|
|Study Chair:||Susan E. Cohn, MD, MPH||Northwestern University|
|Study Chair:||Jennifer Robinson, MD, MPH||Johns Hopkins University|