TuberculosisPhase 2NCT00728507
Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis
A Phase 2 study testing Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid and Isoniazid, Rifampin, Pyrazinamide, Ethambutol in people with Tuberculosis, run by Johns Hopkins University at 3 sites in Brazil.
Trial summary
Although effective therapy for tuberculosis is available, TB continues to cause significant problems worldwide, and rates of multi-drug resistant (MDR) TB cases are on the rise. A major obstacle to the control of TB is poor adherence with lengthy (usually 6 months) and complicated treatment regimens. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid and Isoniazid, Rifampin, Pyrazinamide, Ethambutol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 3 sitesBrazil
- Study dates
- Nov 2009to Apr 2013
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presumptive diagnosis of sputum smear-positive pulmonary TB.
- Age: ≥18 years
- Seven (7) or fewer days of multidrug therapy for TB disease in the preceding 6 months.
- Seven (7) or fewer days of fluoroquinolone therapy in the preceding 3 months.
- Documentation of HIV infection status.
- For HIV seropositive individuals, a CD4 T lymphocyte count of greater than or equal to 200 cells/mm3.
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- Documentation of study baseline laboratory parameters done at, or ≤ 14 days prior to screening:
- AST less than or equal to 2.5 times upper limit of normal.
- Total bilirubin level less than 2.5 times upper limit of normal.
- Creatinine level less than 2 times upper limit of normal.
- Hemoglobin level of at least 8.0 g/dl.
- Platelet count of at least 75,000 mm3.
- Potassium level of at least 3.5.
- Negative pregnancy test (women of childbearing potential).
- Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs).
- Male or nonpregnant, nonnursing female.
- Provision of informed consent.
Who cannot join
- CD4 count < 200 cells/cu mm.
- Presence of active AIDS-related opportunistic infection (other than TB) or active AIDS-related malignancy.
- Known intolerance to any of the study drugs.
- Concomitant disorders or conditions for which any of the study drugs is contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
- Inability to take oral medication.
- Central nervous system TB.
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- Pulmonary silicosis.
- Current or planned therapy, during study phase (intensive phase of TB treatment), with any one or more of the following drugs: quinidine, procainamide, amiodarone, sotalol, disopyramide, terfenadine, cisapride, erythromycin, clarithromycin, phenothiazines, haloperidol, olanzapine, ziprasidone, tricyclic antidepressants, chronic corticosteroids administered either orally or intravenously, chronic fluconazole,chronic itraconazole, chronic ketoconazole, oral or intravenous tacrolimus, oral or intravenous cyclosporine, HIV protease inhibitor, HIV non-nucleoside reverse transcriptase inhibitor.
- Concurrent severe and/or uncontrolled medical or psychiatric condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol.
- Unable or unwilling to receive directly observed therapy and/or adhere with follow-up (e.g. due to residence remote from the study site).
- Refusal of consent.
Trial locations and contacts
3 sites in 1 country.
Brazil3 sites
Centro de Referência Professor Hélio Fraga - ENSP - FIOCRUZ
Curicica, Rio de Janeiro, 22.780-192
Posto de Saude Albert Sabin
Rio de Janeiro, Rio de Janeiro, 20211-110
Hospital Universitario Clementio Fraga Filho
Rio de Janeiro
About this study
Official title: A Phase II Randomized, Open-label Trial of a Rifapentine Plus Moxifloxacin-Based Regimen for Intensive Phase Treatment of Smear-Positive Pulmonary Tuberculosis
Although effective therapy for tuberculosis is available, TB continues to cause significant problems worldwide, and rates of multi-drug resistant (MDR) TB cases are on the rise. A major obstacle to the control of TB is poor adherence with lengthy (usually 6 months) and complicated treatment regimens. Incomplete TB treatment can lead to serious consequences such as increased severity of illness and death, prolonged infectiousness and transmission in the community, and the development of drug resistance. The development of new treatment strategies with more stronger drugs could lead to shorter and simpler regimens. A TB treatment regimen that allowed treatment duration to be meaningfully decreased would have important public health implications.
This trial will compare the effect and safety of a new oral regimen to that of the standard regimen for the first phase of treatment for pulmonary tuberculosis.
Read more
The experimental regimen will consist of the following:
- Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
The standard control intensive phase regimen will consist of the following:
- Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
Following intensive phase therapy (the study phase), all patients will be treated with a non-experimental continuation phase regimen.
In mice, the combination of Moxifloxacin and Rifapentine have cured the animals significantly faster than the standard regimen and this study will be the first step to see if the potential is also there in humans.
- Conditions
- Tuberculosis
- Being tested
- Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid, Isoniazid, Rifampin, Pyrazinamide, Ethambutol
- Keywords
- Tuberculosis, Moxifloxacin, Rifapentine
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rifapentine, Moxifloxacin, Pyrazinamide, IsoniazidDrug
Also called Priftin, Avelox
Rifapentine:150mg tablets, dose = 300mg for subjects <= 45kg and 450mg for those >45kg by mouth once a day for 8 weeks; Moxifloxacin 400mg tablet by mouth once a day for 8 weeks, Isoniazid and Pyrazinamide per standard of care for TB treatment.
Isoniazid, Rifampin, Pyrazinamide, EthambutolDrug
Administered per standard of care for TB treatment
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid. Receives: Drug: Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid |
| 2 | Active comparator | Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid. Receives: Drug: Isoniazid, Rifampin, Pyrazinamide, Ethambutol |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.
LJ culture conversion
Measured: Week 8
To Compare the Safety and Tolerability of the 2 Intensive Phase Regimens.
Study was prematurely terminated and data was not collected for this outcome measure.
Measured: Weekly or more frequent
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2008 (estimated)
- Study startNov 2009
- Primary completionApr 2013
- Study completionApr 2013
Why it stopped: Funding withdrawn
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 (4)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
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Universidade Federal do Rio de Janeiro
- Responsible party
- Sponsor
- Investigators
- Susan Dorman, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00728507
- Sponsor's protocol ID
- 06-0018
- Status last verified
- Mar 2017
- First submitted
- 30 Jul 2008
- Last updated
- 20 Apr 2017
- 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 16574936Nuermberger EL, Yoshimatsu T, Tyagi S, O'Brien RJ, Vernon AN, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med. 2004 Feb 1;169(3):421-6. doi: 10.1164/rccm.200310-1380OC. Epub 2003 Oct 24.
PubMed 14578218Nuermberger EL, Yoshimatsu T, Tyagi S, Williams K, Rosenthal I, O'Brien RJ, Vernon AA, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am J Respir Crit Care Med. 2004 Nov 15;170(10):1131-4. doi: 10.1164/rccm.200407-885OC. Epub 2004 Aug 11.
PubMed 15306535Conde MB, Mello FC, Duarte RS, Cavalcante SC, Rolla V, Dalcolmo M, Loredo C, Durovni B, Armstrong DT, Efron A, Barnes GL, Marzinke MA, Savic RM, Dooley KE, Cohn S, Moulton LH, Chaisson RE, Dorman SE. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis. PLoS One. 2016 May 9;11(5):e0154778. doi: 10.1371/journal.pone.0154778. eCollection 2016.
PubMed 27159505
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Open-label Trial of a Rifapentine Plus Moxifloxacin-Based Regimen for Intensive Phase Treatment of Smear-Positive Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT00728507
- Acronym / sponsor ID
- 06-0018
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, Moxifloxacin, Rifapentine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding withdrawn
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Universidade Federal do Rio de Janeiro
- Study start
- Nov 2009
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 5 Aug 2008 (estimated)
- Results
- Posted 20 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Although effective therapy for tuberculosis is available, TB continues to cause significant problems worldwide, and rates of multi-drug resistant (MDR) TB cases are on the rise. A major obstacle to the control of TB is poor adherence with lengthy (usually 6 months) and complicated treatment regimens. Incomplete TB treatment can lead to serious consequences such as increased severity of illness and death, prolonged infectiousness and transmission in the community, and the development of drug resistance. The development of new treatment strategies with more stronger drugs could lead to shorter and simpler regimens. A TB treatment regimen that allowed treatment duration to be meaningfully decreased would have important public health implications.
This trial will compare the effect and safety of a new oral regimen to that of the standard regimen for the first phase of treatment for pulmonary tuberculosis.
The experimental regimen will consist of the following:
- Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
The standard control intensive phase regimen will consist of the following:
- Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
Following intensive phase therapy (the study phase), all patients will be treated with a non-experimental continuation phase regimen.
In mice, the combination of Moxifloxacin and Rifapentine have cured the animals significantly faster than the standard regimen and this study will be the first step to see if the potential is also there in humans.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Rifapentine, Moxifloxacin, Pyrazinamide, IsoniazidTwo months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid. |
| 2 | Active comparator | Drug: Isoniazid, Rifampin, Pyrazinamide, EthambutolTwo months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Presumptive diagnosis of sputum smear-positive pulmonary TB.
- Age: ≥18 years
- Seven (7) or fewer days of multidrug therapy for TB disease in the preceding 6 months.
- Seven (7) or fewer days of fluoroquinolone therapy in the preceding 3 months.
- Documentation of HIV infection status.
Key exclusion criteria (11 listed)
- CD4 count < 200 cells/cu mm.
- Presence of active AIDS-related opportunistic infection (other than TB) or active AIDS-related malignancy.
- Known intolerance to any of the study drugs.
- Concomitant disorders or conditions for which any of the study drugs is contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
- Inability to take oral medication.
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, Moxifloxacin, Pyrazinamide, IsoniazidAlso: Priftin, AveloxRifapentine:150mg tablets, dose = 300mg for subjects <= 45kg and 450mg for those >45kg by mouth once a day for 8 weeks; Moxifloxacin 400mg tablet by mouth once a day for 8 weeks, Isoniazid and Pyrazinamide per standard of care for TB treatment. | Drug | 1 |
| Isoniazid, Rifampin, Pyrazinamide, EthambutolAdministered per standard of care for TB treatment | Drug | 2 |
Primary outcome
To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.
Time frame: Week 8
LJ culture conversion
To Compare the Safety and Tolerability of the 2 Intensive Phase Regimens.
Time frame: Weekly or more frequent
Study was prematurely terminated and data was not collected for this outcome measure.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: 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.
- Background: PubMed 14578218Nuermberger EL, Yoshimatsu T, Tyagi S, O'Brien RJ, Vernon AN, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med. 2004 Feb 1;169(3):421-6. doi: 10.1164/rccm.200310-1380OC. Epub 2003 Oct 24.
- Background: PubMed 15306535Nuermberger EL, Yoshimatsu T, Tyagi S, Williams K, Rosenthal I, O'Brien RJ, Vernon AA, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am J Respir Crit Care Med. 2004 Nov 15;170(10):1131-4. doi: 10.1164/rccm.200407-885OC. Epub 2004 Aug 11.
- Derived from this study: PubMed 27159505Conde MB, Mello FC, Duarte RS, Cavalcante SC, Rolla V, Dalcolmo M, Loredo C, Durovni B, Armstrong DT, Efron A, Barnes GL, Marzinke MA, Savic RM, Dooley KE, Cohn S, Moulton LH, Chaisson RE, Dorman SE. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis. PLoS One. 2016 May 9;11(5):e0154778. doi: 10.1371/journal.pone.0154778. eCollection 2016.
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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
3 sites 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, Moxifloxacin, Pyrazinamide, Isoniazid and Isoniazid, Rifampin, Pyrazinamide, Ethambutol in people with Tuberculosis, run by Johns Hopkins University at 3 sites in Brazil.
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 11 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: stopped early, as of the sponsor's last update on 20 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Brazil. 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 20 Apr 2017). 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?
To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy. (time frame: Week 8). 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 NCT00728507, which also lists 4 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 20 Apr 2017.