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TBTC Study 31: Rifapentine-containing Tuberculosis Treatment Shortening Regimens (S31/A5349)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Centers for Disease Control and Prevention
Sponsor:
Collaborator:
AIDS Clinical Trials Group
Information provided by (Responsible Party):
Stefan Goldberg, Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT02410772
First received: February 8, 2015
Last updated: July 7, 2016
Last verified: July 2016
  Purpose

The purpose of this study is to determine whether one or two four-month regimens of tuberculosis treatment are as effective as a standard six-month regimen for treatment of pulmonary tuberculosis (TB). All three regimens are administered daily, seven days each week, with direct observation of each dose by a health-care worker at least five of the seven days of each week.

The standard six-month regimen is two months of isoniazid, rifampin, ethambutol, and pyrazinamide followed by four months of isoniazid and rifampin.

The first short regimen is a single substitution of rifapentine for rifampin: two months of isoniazid, rifapentine, ethambutol, and pyrazinamide, followed by two months of isoniazid and rifapentine.

The second short regimen is a double substitution of rifapentine for rifampin and moxifloxacin for ethambutol: two months of isoniazid, rifapentine, moxifloxacin, and pyrazinamide, followed by two months of isoniazid, rifapentine, and moxifloxacin.

Target enrollment is 2500 participants. Each study participant will remain in the study for 18 months in order to include at least 12 months of evaluation of whether the participant's TB recurs.


Condition Intervention Phase
Tuberculosis
Drug: rifapentine
Drug: rifapentine and moxifloxacin
Drug: control
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rifapentine-containing Treatment Shortening Regimens for Pulmonary Tuberculosis: A Randomized, Open-label, Controlled Phase 3 Clinical Trial. TBTC Study 31, ACTG Study A5349

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • TB disease-free survival at twelve months after study treatment assignment [ Time Frame: twelve months after treatment assignment ]
  • Proportion of participants with grade 3 or higher adverse events during study drug treatment [ Time Frame: four or six months ]

Secondary Outcome Measures:
  • TB disease-free survival at eighteen months after study treatment assignment [ Time Frame: eighteen months after treatment assignment ]
  • Proportion of participants who are culture negative at eight weeks [ Time Frame: eight weeks ]
    solid and liquid media considered separately

  • Time to stable sputum culture conversion [ Time Frame: four or six months ]
    solid and liquid media considered separately

  • Speed of decline of sputum viable bacilli by automated MGIT days to detection [ Time Frame: four or six months ]
  • TB disease-free survival at twelve and eighteen months after study treatment assignment assuming all losses to follow-up and non-tuberculosis deaths have an unfavorable outcome [ Time Frame: eighteen months after study treatment assignment ]
    Sensitivity analyses assuming all losses to follow-up and non-tuberculosis deaths have an unfavorable outcome

  • TB disease-free survival at twelve and eighteen months after study treatment assignment assuming all losses to follow-up and non-tuberculosis deaths have a favorable outcome [ Time Frame: eighteen months after study treatment assignment ]
    Sensitivity analyses assuming all losses to follow-up and non-tuberculosis deaths have a favorable outcome

  • Discontinuation of assigned treatment for a reason other than microbiological ineligibility [ Time Frame: four or six months ]
  • Efavirenz maximum concentration, area under the time-concentration curve, and half life [ Time Frame: four months ]
    Among participants with HIV infection receiving efavirenz-based antiretroviral therapy, these values will be used to estimate steady state efavirenz PK parameters including mid-dosing interval concentration


Estimated Enrollment: 2500
Study Start Date: January 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Regimen 1

Eight weeks of daily treatment with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by Eighteen weeks of daily treatment with rifampin and isoniazid

All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose.

study drug doses: rifampin, 600 mg; isoniazid, 300 mg; pyrazinamide, < 55kg 1000 mg, >= 55-75 kg 1500 mg, >75 kg 2000 mg; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg

Drug: control
standard six-month treatment
Experimental: Regimen 2

Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and ethambutol, followed by Nine weeks of daily treatment with rifapentine and isoniazid

All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose.

study drug doses: rifapentine 1200 mg; isoniazid, 300 mg; pyrazinamide, < 55kg 1000 mg, >= 55-75 kg 1500 mg, >75 kg 2000 mg; ethambutol, < 55kg 800 mg, >= 55-75 kg 1200 mg, >75 kg 1600 mg

Drug: rifapentine
Regimen 2: Rifapentine is substituted for rifampin as the basis of 4-month treatment
Other Name: Priftin
Experimental: Regimen 3

Eight weeks of daily treatment with rifapentine, isoniazid, pyrazinamide, and moxifloxacin, followed by Nine weeks of daily treatment with rifapentine, isoniazid, and moxifloxacin

All drugs are administered orally, seven days/week, directly observed by a health care worker at least five of the seven days each week. Pyridoxine (vitamin B6), 25 or 50 mg, is administered with each study dose.

study drug doses: rifapentine 1200 mg; isoniazid, 300 mg; pyrazinamide, < 55kg 1000 mg, >= 55-75 kg 1500 mg, >75 kg 2000 mg; moxifloxacin, 400 mg

Drug: rifapentine and moxifloxacin
Regimen 3: In addition to the single substitution described for regimen 2, a second substitution is added, of moxifloxacin for ethambutol.
Other Name: Priftin and Avelox

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Suspected pulmonary tuberculosis plus one or both of the following: a) at least one sputum specimen positive for acid-fast bacilli on smear microscopy OR b) at least one sputum specimen positive for M. tuberculosis by Xpert MTB/RIF testing, with semiquantitative result of 'medium' or 'high' and rifamycin resistance not detected.
  • Age twelve (12) years or older
  • A verifiable address or residence location that is readily accessible for visiting, and willingness to inform the study team of any change of address during the treatment and follow-up period.
  • Women of child-bearing potential who are not surgically sterilized must agree to practice a barrier method of contraception or abstain from heterosexual intercourse during study drug treatment.
  • Documentation of HIV infection status.
  • For HIV-positive individuals, CD4 T cell count greater than or equal to 100 cells/mm3 based on testing performed at or within 30 days prior to screening.
  • Laboratory parameters done at or within 14 days prior to screening:

    • Serum or plasma alanine aminotransferase (ALT) less than or equal to 3 times the upper limit of normal
    • Serum or plasma total bilirubin less than or equal to 2.5 times the upper limit of normal
    • Serum or plasma creatinine level less than or equal to 2 times the upper limit of normal
    • Serum or plasma potassium level greater than or equal to 3.5 meq/L
    • Hemoglobin level of 7.0 g/dL or greater
    • Platelet count of 100,000/mm3 or greater
  • For women of childbearing potential, a negative pregnancy test at or within seven (7) days prior to screening
  • Karnofsky score greater than or equal to 60
  • Written informed consent

Exclusion Criteria:

  • Pregnant or breast-feeding.
  • Unable to take oral medications.
  • Previously enrolled in this study.
  • Received any investigational drug in the past 3 months.
  • More than five (5) days of treatment directed against active tuberculosis within 6 months preceding initiation of study drugs.
  • More than five (5) days of systemic treatment with any one or more of the following drugs within 30 days preceding initiation of study drugs: isoniazid, rifampin, rifabutin, rifapentine, ethambutol, pyrazinamide, kanamycin, amikacin, streptomycin, capreomycin, moxifloxacin, levofloxacin, gatifloxacin, ofloxacin, ciprofloxacin, other fluoroquinolones, ethionamide, prothionamide, cycloserine, terizidone, para-aminosalicylic acid, linezolid, clofazimine, delamanid or bedaquiline.
  • Known history of prolonged QT syndrome.
  • Suspected or documented tuberculosis involving the central nervous system and/or bones and/or joints, and/or miliary tuberculosis and/or pericardial tuberculosis.
  • Current or planned use within six months following enrollment of one or more of the following medications: HIV protease inhibitors, HIV integrase inhibitors, HIV entry and fusion inhibitors, HIV non-nucleoside reverse transcriptase inhibitors other than efavirenz, quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine. Individuals who are currently taking efavirenz-based antiretroviral treatment or for whom initiation of efavirenz-based antiretroviral treatment is planned within 17 weeks following enrollment may participate.
  • Weight less than 40.0 kg.
  • Known allergy or intolerance to any of the study medications.
  • Individuals will be excluded from enrollment if, at the time of enrollment, their M. tuberculosis isolate is already known to be resistant to any one or more of the following: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
  • Other medical conditions, that, in the investigator's judgment, make study participation not in the individual's best interest.
  • Current or planned incarceration or other involuntary detention.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02410772

Contacts
Contact: Stefan V Goldberg, MD 404-639-5339 ssg3@cdc.gov
Contact: Ekaterina (Katya) Kurbatova, MD, PhD, MPH 404-639-2017 ies3@cdc.gov

  Show 38 Study Locations
Sponsors and Collaborators
Centers for Disease Control and Prevention
AIDS Clinical Trials Group
Investigators
Principal Investigator: Susan Dorman, MD Johns Hopkins University
Principal Investigator: Payam Nahid, MD, MPH University of California at San Francisco
  More Information

Responsible Party: Stefan Goldberg, Medical Officer, Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT02410772     History of Changes
Other Study ID Numbers: 6655
Study First Received: February 8, 2015
Last Updated: July 7, 2016
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Data being collected in CDISC format.

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Moxifloxacin
Fluoroquinolones
Rifapentine
Ethambutol
Rifampin
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Leprostatic Agents
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers

ClinicalTrials.gov processed this record on March 24, 2017