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N Engl J Med. 2011 Dec 8;365(23):2155-66. doi: 10.1056/NEJMoa1104875.

Three months of rifapentine and isoniazid for latent tuberculosis infection.

Collaborators (205)

Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Khan A, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Horsburgh CR Jr, Chaisson RE, McSherry G, Arevalo B, Weis SE, Fernandez M, King B, Turk L, Shafer N, Stevenson G, Bayona G, Dean R, Helal J, Burgess G, Conde MB, Mello FC, Efron A, Loredo C, Fortuna MB, Cailleaux-Cezar M, Guerra RL, Mota G, Felix C, Kritski A, de Oliveira V, Sacramento Cdos S, Wing R, Wing D, Valenzuela D, Gonzalez J, Uribe J, Smith BR, Weiner M, Engle M, Jimenez JA, Pavon H, Rodriguez V, West KB, Dooley D, Hospenthal D, Sterling T, Hammock LR, Kerrigan A, Redd B, Montgomery I, Miller K, Jones BE, Escalante P, Molina P, Silva C, Grbic A, Brown M, Oamar B, Rayos E, Luken C, Schluger NW, Burzynski J, Lozano V, Wolk M, Mangura BT, Reichman LB, McSherry G, Lardizabal A, Leus MC, Owens M, Napolitano E, Kellert L, Anokute V, Burman W, Reves R, Belknap R, Cohn D, Tapy J, Sanchez G, Luna L, Catanzaro A, LoBue P, Moser K, Tracy M, Francisco P, Davis J, Menzies RI, Schwartzman K, Greenaway C, Lands L, Mannix S, Brassard P, Mortezai B, Rabinovitch B, Pelletier M, Valiquette C, Tremblay J, Plaisir PA, Binet R, Narita M, Nolan CM, Goldberg S, Schwartz D, Deretsky L, Stone M, Friedly C, Cayla JA, Miró JM, Sambeat MA, López Colomés JL, Martinez JA, Martinez-Lacasa X, Orcau A, Sanchez P, Tortajada C, Ocana I, Millet JP, Moreno A, Nelson J, Sued O, de Souza ML, Jiménez MA, del Baño L, Fina L, Nahid P, Hopewell P, Daley C, Jasmer R, Merrifield C, Stanton W, Rudoy I, Israel J, Chaisson R, Dorman S, Fisher J, Maltas G, Hackman J, Hamilton CD, Stout J, Mosher A, Hecker EJ, Ho B, Rich E, Bernardo J, Saukkonen J, Murphy C, Brett-Curran D, Pachucki CT, Lee A, Marantz S, Samuel MP, Zulaga A, El-Sadr WM, Klein M, Badshah C, Schicchi JS, Hirsh-Moverman Y, Ray SM, Holland DP, Dixon D, Mohamed O, Folami K, Bush J, Simpson CD, Barika G, Favors WN, Snow N, Bhattacharya M, Lippold S, Clapp W, Fabre J, Fitzgerald JM, Elwood K, Hernandez E, Peyvandi B, Alasaly K, Bakhtawar I, Wilson F, Wassler P, Arnold A, Haden K, Owen J, Kepron W, Hershfield E, Roth M, Izon GA, Guy E, Lahart C, Scott T, Nickson R, Gordin F, Benator D, Conwell DS, Condos R, Rom W, Sandman L, Ahmed A, Horton J, West J, Quinn E.

Author information

  • 1Vanderbilt University School of Medicine, Nashville, TN, USA. timothy.sterling@vanderbilt.edu

Abstract

BACKGROUND:

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.

METHODS:

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%.

RESULTS:

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).

CONCLUSIONS:

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.).

Comment in

PMID:
22150035
[PubMed - indexed for MEDLINE]
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