Trial of High-Dose Rifampin in Patients With TB (HIRIF)
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ClinicalTrials.gov Identifier: NCT01408914 |
Recruitment Status :
Completed
First Posted : August 3, 2011
Results First Posted : July 13, 2017
Last Update Posted : November 20, 2017
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Tracking Information | |||||||
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First Submitted Date ICMJE | August 2, 2011 | ||||||
First Posted Date ICMJE | August 3, 2011 | ||||||
Results First Submitted Date ICMJE | May 3, 2017 | ||||||
Results First Posted Date ICMJE | July 13, 2017 | ||||||
Last Update Posted Date | November 20, 2017 | ||||||
Study Start Date ICMJE | September 2013 | ||||||
Actual Primary Completion Date | April 2016 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Steady State Pharmacokinetic Exposure of RIF [ Time Frame: At any time during the intensive phase of treatment, after steady state has been reached (at a minimum, after 14 days of daily RIF delivery) ] The endpoint is the (dimensionless) ratio of AUC0-6 mcg/ml*h to MIC99.9 mcg/ml
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Original Primary Outcome Measures ICMJE |
Difference in steady state pharmacokinetic exposure of RIF and 25-desacetyl-rifampin. [ Time Frame: after 14 days of daily RIF delivery ] | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Trial of High-Dose Rifampin in Patients With TB | ||||||
Official Title ICMJE | Randomized Trial of High-Dose Rifampin in Patients With New, Smear-Positive TB | ||||||
Brief Summary | The purpose of this study is to evaluate the potential of high doses of rifampin (RIF) to shorten treatment for tuberculosis (TB) without causing more adverse events. The hypotheses are that higher doses of RIF will result in higher blood concentrations of RIF; higher blood concentrations will result in tuberculosis bugs being killed more quickly; and, both of these will happen without more adverse events. Patients with active, infectious, drug-susceptible TB who agree to participate will be randomly assigned to 1 of 3 doses of RIF. All patients will also receive standard doses of regular (3) companion drugs for 2 months of daily, supervised therapy. The study will assess the following among the 3 study arms (oral doses of RIF 10, 15 & 20 mg/kg/day) during the initial 8 weeks of treatment: 1) the amount of RIF in the blood after at least 14 days of treatment; 2) the difference in the number of tuberculosis bugs killed; 3) the frequency of adverse events. | ||||||
Detailed Description | This is a Phase II, multi-site, dose-ranging trial comparing 3 doses of RIF in a multidrug regimen for treatment of smear-positive, pulmonary TB. The intervention phase of this prospective, randomized, double-blinded trial will last 8 weeks, the duration of the standard "intensive" phase for short-course chemotherapy for TB. During that time, subjects will receive the following companion drugs: isoniazid (INH, 5 mg/kg/day), ethambutol (EMB, 20 mg/kg/day), and pyrazinamide (PZA, 25 mg/kg/day), pyridoxine (50 mg), the standard doses used in treatment. Subjects will also be randomized to receive one of the following weight-based doses of the study drug, rifampin (RIF): 10 mg/kg/day (standard dose, control), 15 mg/kg/day (intervention 1), 20 mg/kg/day (intervention 2). All patients will receive at least standard dose of RIF, the efficacy of which in multidrug-treatment for TB is well established. Placebo will be used to control only the additional RIF capsules provided in the intervention arms. Subjects, clinicians, and laboratory staff will be blinded to study arm. All patients in the same weight band will receive the same total number of tablets (fixed-dose combination plus RIF and/or placebo). Blinding is essential to reduce the probability of biased reporting of adverse events. After randomization, other covariates that may result in heterogeneity within strata (e.g., presence of cavitation, HIV serostatus), will be adjusted for in analyses. It is important to maintain the ability to measure the effect (if any) of these potential characteristics on treatment outcome. If we were to stratify on these characteristics, we could not estimate their confounding (or interaction) effect. All doses will be delivered orally and fully supervised. All patients will receive weight-based doses of fixed-dose combinations according to package inserts. This will be supplemented by active RIF capsules or placebos, or both, according to weight and treatment arm. They will also all receive 50 mg of pyridoxine to prevent peripheral neuropathy, a common side effect of INH. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Tuberculosis | ||||||
Intervention ICMJE | Drug: Higher-Dose Rifampin
The intervention phase of this trial will last 8 weeks. During that time, subjects will receive the following companion drugs: isoniazid (INH, 5 mg/kg/day), ethambutol (EMB, 20 mg/kg/day), and pyrazinamide (PZA, 25 mg/kg/day), pyridoxine (50 mg), the standard doses used in treatment. Subjects will also be randomized to receive one of the following weight-based doses of the study drug, rifampin (RIF): 10 mg/kg/day (standard dose, control), 15 mg/kg/day (intervention 1), 20 mg/kg/day (intervention 2). All patients will receive at least standard dose of RIF, the efficacy of which in multidrug-treatment for TB is well established. Placebo will be used to control only the additional RIF capsules provided in the intervention arms.
Other Name: rifadin, rifampicin
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE |
180 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Actual Study Completion Date ICMJE | April 2016 | ||||||
Actual Primary Completion Date | April 2016 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 60 Years (Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Peru, United Kingdom, United States | ||||||
Removed Location Countries | Brazil | ||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT01408914 | ||||||
Other Study ID Numbers ICMJE | 11-0050 5U01AI091429-03 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product | Not Provided | ||||||
IPD Sharing Statement ICMJE | Not Provided | ||||||
Current Responsible Party | Carole Mitnick, Harvard University Faculty of Medicine | ||||||
Original Responsible Party | Carole D. Mitnick, Harvard Medical School | ||||||
Current Study Sponsor ICMJE | Harvard University Faculty of Medicine | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Harvard University Faculty of Medicine | ||||||
Verification Date | October 2017 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |