TuberculosisPhase 2NCT00814671
Study of Daily Rifapentine for Pulmonary Tuberculosis
A Phase 2 study testing Rifapentine 450, Rifapentine 600 and Rifampin in people with Tuberculosis, run by Johns Hopkins University at 1 site in South Africa.
Trial 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 tuberculosis (TB). Funding Source- FDA Office of Orphan Products Development (OOPD) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Rifapentine 450, Rifapentine 600 and Rifampin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 1 siteSouth Africa
- Study dates
- Apr 2010to Sep 2014
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- No prior history of tuberculosis disease or tuberculosis treatment
- No treatment with fluoroquinolones in the 2 months preceding initiation of study drugs.
- Age > 18 years
- Weight ≥ 50 kg and ≤ 80 kg
- Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix)
Show all 17Show fewer
- Signed informed consent
- Ability to adhere with study follow-up
- 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.
- HIV negative, or HIV-positive with CD4 > 200 cells/cu mm
- 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)
Who cannot join
- Pregnant or breast-feeding
- Known intolerance or allergy to any of the study drugs
- 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.
- 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.
- Any medical or psychosocial condition, which, in the view of the study investigator, makes study participation inadvisable.
- Pulmonary silicosis
- Central nervous system TB
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Universiy of Cape Town Lung Institute
Cape Town, Western Cape, 7937
About this study
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
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 tuberculosis (TB).
Funding Source- FDA Office of Orphan Products Development (OOPD)
Read the 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.
- Conditions
- Tuberculosis
- Being tested
- Rifapentine 450, Rifapentine 600, Rifampin
- Keywords
- Tuberculosis, Pharmacokinetics
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifapentine 450Drug
Also called Priftin
rifapentine 450 mg
Rifapentine 600Drug
Also called Priftin
rifapentine 600 mg
RifampinDrug
Also called Rifampacin
rifampin 600 mg
| Study group | Role | What they receive |
|---|---|---|
| RPT450 | Experimental | Rifapentine 450mg daily Receives: Drug: Rifapentine 450 |
| RIF 600 | Active comparator | Rifampin 600mg daily Receives: Drug: Rifampin |
| RPT 600 | Experimental | Rifapentine 600mg daily Receives: Drug: Rifapentine 600 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8
Measured: 8 weeks
Tolerability
percentage of participants discontinuing assigned treatment
Measured: 10 weeks
Secondary outcomes (3)
Time to Stable Culture Conversion on Solid Medium
Time to stable culture conversion (in days) on Lowenstein Jensen solid medium
Measured: 12 weeks
Time to Stable Culture Conversion on Liquid MGIT Media
Time (in days) to stable culture conversion on liquid MGIT media
Measured: 12 weeks
Pharmacokinetics of Rifapentine
area under the concentration time curve (AUC[0-24]) for rifapentine administered once daily at doses of 450 mg or 600 mg in the context of multi drug intensive phase TB treatment
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2008 (estimated)
- Study startApr 2010
- Primary completionJun 2013
- Study completionSep 2014
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cape Town Lung Institute, University of Cape Town
- Responsible party
- Sponsor
- Investigators
- Susan Dorman, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00814671
- Sponsor's protocol ID
- NA_00019095
- Status last verified
- Jan 2018
- First submitted
- 24 Dec 2008
- Last updated
- 6 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rosenthal IM, Williams K, Tyagi S, Peloquin CA, Vernon AA, Bishai WR, Grosset JH, Nuermberger EL. Potent twice-weekly rifapentine-containing regimens in murine tuberculosis. Am J Respir Crit Care Med. 2006 Jul 1;174(1):94-101. doi: 10.1164/rccm.200602-280OC. Epub 2006 Mar 30.
PubMed 16574936Rosenthal IM, Williams K, Tyagi S, Vernon AA, Peloquin CA, Bishai WR, Grosset JH, Nuermberger EL. Weekly moxifloxacin and rifapentine is more active than the denver regimen in murine tuberculosis. Am J Respir Crit Care Med. 2005 Dec 1;172(11):1457-62. doi: 10.1164/rccm.200507-1072OC. Epub 2005 Sep 1.
PubMed 16141439
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00814671
- Acronym / sponsor ID
- NA_00019095
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, Pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- University of Cape Town Lung Institute, University of Cape Town
- Study start
- Apr 2010
- Primary completion
- Jun 2013 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 25 Dec 2008 (estimated)
- Results
- Posted 28 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 tuberculosis (TB).
Funding Source- FDA Office of Orphan Products Development (OOPD)
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| RPT450 | Experimental | Drug: Rifapentine 450Rifapentine 450mg daily |
| RIF 600 | Active comparator | Drug: RifampinRifampin 600mg daily |
| RPT 600 | Experimental | Drug: Rifapentine 600Rifapentine 600mg daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
- No prior history of tuberculosis disease or tuberculosis treatment
- No treatment with fluoroquinolones in the 2 months preceding initiation of study drugs.
- Age > 18 years
- Weight ≥ 50 kg and ≤ 80 kg
Key exclusion criteria (7 listed)
- Pregnant or breast-feeding
- Known intolerance or allergy to any of the study drugs
- 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.
- 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.
- Any medical or psychosocial condition, which, in the view of the study investigator, makes study participation inadvisable.
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 |
|---|---|---|
| Rifapentine 450Also: Priftinrifapentine 450 mg | Drug | RPT450 |
| Rifapentine 600Also: Priftinrifapentine 600 mg | Drug | RPT 600 |
| RifampinAlso: Rifampacinrifampin 600 mg | Drug | RIF 600 |
Primary outcome
Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8
Time frame: 8 weeks
Tolerability
Time frame: 10 weeks
percentage of participants discontinuing assigned treatment
3 secondary outcomes
Time to Stable Culture Conversion on Solid Medium
Time frame: 12 weeks
Time to Stable Culture Conversion on Liquid MGIT Media
Time frame: 12 weeks
Pharmacokinetics of Rifapentine
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 16574936Rosenthal IM, Williams K, Tyagi S, Peloquin CA, Vernon AA, Bishai WR, Grosset JH, Nuermberger EL. Potent twice-weekly rifapentine-containing regimens in murine tuberculosis. Am J Respir Crit Care Med. 2006 Jul 1;174(1):94-101. doi: 10.1164/rccm.200602-280OC. Epub 2006 Mar 30.
- Results publication: PubMed 16141439Rosenthal IM, Williams K, Tyagi S, Vernon AA, Peloquin CA, Bishai WR, Grosset JH, Nuermberger EL. Weekly moxifloxacin and rifapentine is more active than the denver regimen in murine tuberculosis. Am J Respir Crit Care Med. 2005 Dec 1;172(11):1457-62. doi: 10.1164/rccm.200507-1072OC. Epub 2005 Sep 1.
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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.
Susan Dorman, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rifapentine 450, Rifapentine 600 and Rifampin in people with Tuberculosis, run by Johns Hopkins University at 1 site in South Africa.
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 17 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 6 Feb 2018. 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 South Africa. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 28 Sep 2016). 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?
Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8 (time frame: 8 weeks). The study lists 2 primary outcomes in all. 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 NCT00814671, 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 6 Feb 2018.