Three Months of Rifapentine and Isoniazid for Latent Tuberculosis Infection

Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In this study, 3 months of weekly isoniazid plus rifapentine (12 doses) was found to be noninferior to 9 months of isoniazid alone. Tuberculosis results in near...

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Vydáno v:The New England journal of medicine Ročník 365; číslo 23; s. 2155 - 2166
Hlavní autoři: Sterling, Timothy R, Villarino, M. Elsa, Borisov, Andrey S, Shang, Nong, Gordin, Fred, Bliven-Sizemore, Erin, Hackman, Judith, Hamilton, Carol Dukes, Menzies, Dick, Kerrigan, Amy, Weis, Stephen E, Weiner, Marc, Wing, Diane, Conde, Marcus B, Bozeman, Lorna, Horsburgh, C. Robert, Chaisson, Richard E
Médium: Journal Article
Jazyk:angličtina
Vydáno: Waltham, MA Massachusetts Medical Society 08.12.2011
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ISSN:0028-4793, 1533-4406, 1533-4406
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Abstract Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In this study, 3 months of weekly isoniazid plus rifapentine (12 doses) was found to be noninferior to 9 months of isoniazid alone. Tuberculosis results in nearly 2 million deaths annually worldwide. 1 More than 2 billion persons are infected with Mycobacterium tuberculosis, 2 and from this reservoir active tuberculosis will develop in millions of persons in coming decades. Treatment of latent M. tuberculosis infection among the persons at highest risk for progression to active disease is an important strategy for tuberculosis control and elimination. 3 – 6 The current standard regimen for the treatment of latent M. tuberculosis infection is 9 months of daily isoniazid. 3 The efficacy for isoniazid was found to be 69 to 93% in a study that was published in 1982 (before the . . .
AbstractList Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.BACKGROUNDTreatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%.METHODSWe conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%.In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001).RESULTSIn the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001).The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.).CONCLUSIONSThe use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.).
Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In this study, 3 months of weekly isoniazid plus rifapentine (12 doses) was found to be noninferior to 9 months of isoniazid alone. Tuberculosis results in nearly 2 million deaths annually worldwide. 1 More than 2 billion persons are infected with Mycobacterium tuberculosis, 2 and from this reservoir active tuberculosis will develop in millions of persons in coming decades. Treatment of latent M. tuberculosis infection among the persons at highest risk for progression to active disease is an important strategy for tuberculosis control and elimination. 3 – 6 The current standard regimen for the treatment of latent M. tuberculosis infection is 9 months of daily isoniazid. 3 The efficacy for isoniazid was found to be 69 to 93% in a study that was published in 1982 (before the . . .
Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion. We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%. In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.).
BackgroundTreatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion.MethodsWe conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%.ResultsIn the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001).ConclusionsThe use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.)
Author Bliven-Sizemore, Erin
Wing, Diane
Horsburgh, C. Robert
Weiner, Marc
Menzies, Dick
Conde, Marcus B
Kerrigan, Amy
Chaisson, Richard E
Borisov, Andrey S
Bozeman, Lorna
Weis, Stephen E
Villarino, M. Elsa
Hamilton, Carol Dukes
Sterling, Timothy R
Shang, Nong
Hackman, Judith
Gordin, Fred
Author_xml – sequence: 1
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  surname: Sterling
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– sequence: 3
  givenname: Andrey S
  surname: Borisov
  fullname: Borisov, Andrey S
– sequence: 4
  givenname: Nong
  surname: Shang
  fullname: Shang, Nong
– sequence: 5
  givenname: Fred
  surname: Gordin
  fullname: Gordin, Fred
– sequence: 6
  givenname: Erin
  surname: Bliven-Sizemore
  fullname: Bliven-Sizemore, Erin
– sequence: 7
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  surname: Hackman
  fullname: Hackman, Judith
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  surname: Hamilton
  fullname: Hamilton, Carol Dukes
– sequence: 9
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  fullname: Menzies, Dick
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  surname: Kerrigan
  fullname: Kerrigan, Amy
– sequence: 11
  givenname: Stephen E
  surname: Weis
  fullname: Weis, Stephen E
– sequence: 12
  givenname: Marc
  surname: Weiner
  fullname: Weiner, Marc
– sequence: 13
  givenname: Diane
  surname: Wing
  fullname: Wing, Diane
– sequence: 14
  givenname: Marcus B
  surname: Conde
  fullname: Conde, Marcus B
– sequence: 15
  givenname: Lorna
  surname: Bozeman
  fullname: Bozeman, Lorna
– sequence: 16
  givenname: C. Robert
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  surname: Chaisson
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BackLink http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25267878$$DView record in Pascal Francis
https://www.ncbi.nlm.nih.gov/pubmed/22150035$$D View this record in MEDLINE/PubMed
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Greenaway, Christina
Kellert, Laurie
Stevenson, Gloria
Sanchez, Grace
Valenzuela, Diana
Mello, Fernanda C Q
Hammock, Linda R
Shang, Nong
King, Barbara
Burgess, Gerry
Schluger, Neil W
Tapy, Jan
Grbic, Angela
Escalante, Patricio
Mota, Gisele
Sacramento, Claudeci dos Santos
Uribe, Juan
Shafer, Norma
de Oliveira, Valéria
Rodriguez, Victoria
Davis, Judy
Anokute, Veronica
Hackman, Judith
Napolitano, Eileen
Mannix, Sharyn
Kritski, Afranio
Schwartzman, Kevin
Engle, Melissa
Tracy, Mark
Helal, Joseph
Lozano, Vilma
Efron, Anne
Brassard, Paul
Burzynski, Joseph
Fortuna, Millene Barty S
Arevalo, Bert
Wing, Diane
Conde, Marcus B
West, Kevin B
Luna, Laurie
Oamar, Bonifacia
Turk, Lee
Cailleaux-Cezar, Michelle
Jimenez, Jose A
McSherry, George
Burman, William
Redd, Belinda
Lardizabal, Alfred
Sterling, Timothy R
Wolk, Magda
Guerra, Renata L
Belknap, Robert
Miller, Kathleen
Horsburgh, Jr, C Robert
Mangura, Bonita T
Francisco, Peach
Pavon, Hipolito
Sterling, Timothy
Luken, Celia
Rayos, Ermelinda
Weiner, Marc
Chaisson, Richard E
Lands, Larry
Brown, Maria
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Snippet Treatment of latent TB is an important public-health strategy, but 9 months of daily isoniazid (270 doses) poses challenges for compliance. In this study, 3...
Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of...
BackgroundTreatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard...
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SubjectTerms Adult
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - administration & dosage
Antitubercular Agents - adverse effects
Bacterial diseases
Biological and medical sciences
Directly Observed Therapy
Drug Administration Schedule
Drug Therapy, Combination
Follow-Up Studies
General aspects
Hepatotoxicity
HIV
Human bacterial diseases
Human immunodeficiency virus
Humans
Infections
Infectious diseases
Intention to Treat Analysis
Isoniazid
Isoniazid - administration & dosage
Isoniazid - adverse effects
Male
Medical sciences
Middle Aged
Motivation
Pharmacology. Drug treatments
Prospective Studies
Rifampin - administration & dosage
Rifampin - adverse effects
Rifampin - analogs & derivatives
Risk Factors
Self Administration
Skin
Tuberculosis
Tuberculosis - drug therapy
Tuberculosis - epidemiology
Tuberculosis - prevention & control
Tuberculosis and atypical mycobacterial infections
Virus Latency
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