Study of Daily Rifapentine for Pulmonary Tuberculosis
Information source: Johns Hopkins University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Tuberculosis
Intervention: Rifapentine (Drug); Rifapentine (Drug); Rifampin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Johns Hopkins University Official(s) and/or principal investigator(s): Susan Dorman, MD, Principal Investigator, Affiliation: Johns Hopkins University
Summary
The goal of this Phase 2 study is to determine the microbiological activity and safety of
rifapentine when given as a component of multidrug intensive phase treatment of
smear-positive pulmonary TB.
Funding Source- FDA OOPD
Clinical Details
Official title: A Phase 2 Randomized, Open-label Trial of Daily Rifapentine 450mg or 600mg in Place of Rifampicin 600mg for Intensive Phase Treatment of Smear-positive Pulmonary Tuberculosis
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To estimate the microbiological activity of rifapentine administered at once daily doses of 450 mg and 600 mg based on proportion of participants with culture conversionTo estimate the frequency of side effects of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment
Secondary outcome: To evaluate the microbiological activity of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment, based on time to sputum culture conversionTo evaluate the microbiological activity of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment, based on time to culture growth in MGIT liquid media To describe the pharmacokinetics of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment To determine if rifapentine exposures are associated with microbiological activity To determine if rifapentine exposures are associated with safety To compare Lowenstein Jensen and Bactec MGIT media with respect to proportion of participants with 8-week culture conversion and time to culture conversion
Detailed description:
Prospective phase II, open-label, single center study in which each experimental rifapentine
regimen is evaluated using a two-stage design. Adults (HIV-negative, or HIV-positive with
CD4 > 200 cells/cu mm) suspected to have pulmonary tuberculosis who meet eligibility
criteria will be randomized to receive one of three intensive phase regimens. Intensive
phase regimens will consist of once daily isoniazid, pyrazinamide, and ethambutol, plus one
of the following: rifampin 600 mg once daily OR rifapentine 450 mg once daily OR rifapentine
600 mg once daily. Randomization will be stratified by presence/absence of cavitation on
baseline chest radiograph. In Stage 1, 15 subjects will be randomized to each arm,
following which there will be an enrollment pause for efficacy and safety assessment. Any
rifapentine regimen for which fewer than 6 of 11 evaluable participants have week 8 culture
conversion will be discarded.
Stage 2 will randomize subjects into the remaining "accepted arms" with a maximum of 36
additional subjects per arm.
All subjects will continue TB treatment with a conventional continuation phase treatment.
Study Site
Study subjects will be recruited from the University of Cape Town inpatient wards and
outpatient clinics.
Estimated Study Duration
It is estimated that 18 months will be required for recruitment and enrollment of study
subjects. The estimated duration of participation for each study subject is 18 months,
including 2 months of experimental intensive phase TB treatment, 4 months of
non-experimental conventional continuation phase TB treatment, and an additional 12 months
for follow-up for TB relapse.
Study Management
Study subjects will have study visits on days 0, 7, 14, 21, 28, 35, 42, 49, and 56 for
sputum collection and adverse event assessment. Safety laboratory monitoring will be
performed on days 14, 28, 42, and 56 and will consist of complete blood count, serum alanine
aminotransferase, serum total bilirubin, and serum creatinine. Steady state pharmacokinetic
analysis will be performed on approximately day 28. Subjects will have additional study
visits at week 10 and at months 4, 6, 12, and 18.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of
expectorated sputum. Patients having extra-pulmonary manifestations of tuberculosis,
in addition to smear-positive pulmonary disease, are eligible for enrollment.
2. No prior history of tuberculosis disease or tuberculosis treatment
3. No treatment with fluoroquinolones in the 2 months preceding initiation of study
drugs.
4. Age > 18 years
5. Weight ≥ 50 kg and ≤ 80 kg
6. Karnofsky score of at least 60 (requires occasional assistance but is able to care
for most of his/her needs; see Appendix)
7. Signed informed consent
8. Ability to adhere with study follow-up
9. Women with child-bearing potential must agree to practice an adequate (barrier)
method of birth control or to abstain from heterosexual intercourse during study
therapy.
10. HIV negative, or HIV-positive with CD4 > 200 cells/cu mm
11. Laboratory parameters done at, or 14 days prior to, screening (with results available
for review by study personnel):
- Serum alanine aminotransferase (ALT) activity ≤ 2 times the upper limit of
normal
- Serum total bilirubin level ≤ 2 times the upper limit of normal
- Serum creatinine level less than or equal to the upper limit of normal
- Hemoglobin level of at least 7. 0 g/dL
- Platelet count of at least 100,000/mm3
- Negative pregnancy test (women of childbearing potential)
Exclusion Criteria:
1. Pregnant or breast-feeding
2. Known intolerance or allergy to any of the study drugs
3. Concomitant disorders or conditions for which isoniazid (INH), rifamycins,
pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe
hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty
arthritis.
4. Current or planned therapy, during the intensive phase of TB therapy with
cyclosporine or tacrolimus, or HIV antiretroviral (ARV) therapy, which have
unacceptable interactions with rifamycins.
5. Any medical or psychosocial condition, which, in the view of the study investigator,
makes study participation inadvisable.
6. Pulmonary silicosis
7. Central nervous system TB
Locations and Contacts
Universiy of Cape Town Lung Institute, Cape Town, Western Cape 7937, South Africa
Additional Information
Starting date: April 2010
Last updated: September 25, 2014
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