Clinical trial NCT06253715: Shortened Regimen for Drug-susceptible TB in Children
Official title: Shortened Regimen for Drug-susceptible TB in Children
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Tuberculosis
Tuberculosis, Pulmonary
Tuberculosis, Lymph Node
Mycobacterium Tuberculosis
Keywords: tuberculosis
pediatric
stratified medicine
shortened regimen
rifapentine
moxifloxacin
dolutegravir
drug-susceptible
lymph node
pulmonary
infections
TB
mycobacterium infections
respiratory tract infections
lung diseases
antitubercular agents
respiratory tract diseases
child
paediatric
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: United States Agency for International Development (USAID)
First posted: 2024-02-12
Enrollment: 860
Sex: ALL
Minimum age (years): 0
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: International, multicenter, randomized, controlled, open-label, non-inferiority
Primary purpose: TREATMENT

Brief summary: While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.

Detailed description: In previously untreated individuals with presumed drug-susceptible pulmonary and or peripheral lymph node TB treated with eight weeks of rifapentine, isoniazid, pyrazinamide and moxifloxacin (2HPZM), all given daily throughout, the proportion of participants who experience absence of cure (unsuccessful outcome) will not be inferior to that observed in participants who are treated with the standard regimen (eight weeks of rifampin, isoniazid, pyrazinamide, with or without ethambutol followed by 8 to 16 weeks of rifampin plus isoniazid depending on disease severity) all given daily throughout.

Eligibility criteria: Inclusion Criteria:

* Parent or guardian is willing and able to provide written informed consent for potential participant's study participation; in addition, when applicable per Ethics Committee/Institutional Review Board (EC/IRB) policies and procedures, potential participant is willing and able to provide assent for study participation.
* At Entry, age of less than 10 years.
* At Entry, weight 3 kilograms (kg) or greater.
* At Entry, diagnosed with TB disease, defined as:

  * Pulmonary (including pleural effusion) and/or lymph node (extra-thoracic and/or intra-thoracic) TB with or without bacteriologic confirmation;
  * Clinician has decided to treat with standard first-line drug-susceptible TB regimen.
* Known HIV status or HIV testing in progress based on meeting testing requirements.
* Has normal, Grade 1 or 2 test results for all of the following done at or within 14 days of Entry (including the most recent):

  * Alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal;
  * Total bilirubin less than or equal to 2.5 times the upper limit of normal;
  * Potassium level of 3.0 milliequivalent/L or greater;
  * Hemoglobin level of 7.0 g/dL or greater;
  * Platelet count of 100,000/mm3 or greater;
  * Estimated glomerular filtration rate (eGFR; bedside Schwartz formula) 60 mL/min/1.73m2 or higher.
* For children living with HIV:

  * On antiretroviral therapy (ART) at Entry: Must be on, or able to be switched to a dolutegravir-based regimen at or prior to Entry;
  * Not on ART at Entry: Planned initiation of dolutegravir before or at study Week 4.
* For participants who have reached menarche or who are engaging in sexual activity (self-reported): negative serum or urine pregnancy test within 7 days of Entry.
* For participants who are engaging in sexual activity that could lead to pregnancy (self-reported): agrees to practice at least one non-hormonal method of contraception or abstain from heterosexual intercourse during study drug treatment and for 30 days after stopping study medications. Non-hormonal methods include:

  * Male or female condoms
  * Diaphragm or cervical cap (with spermicide, if available)
  * Non-hormonal intrauterine device (IUD) or intrauterine system (IUS)
* At Entry, intends to remain in the catchment area of the study site for the duration of study follow-up or willingness to be followed up beyond the catchment area if/when applicable, as determined by the site investigator based on participant/parent/guardian report.

Exclusion Criteria:

* Presumed or documented extra-pulmonary TB involving the central nervous system and/or bones and/or joints, and/or miliary TB, and/or pericardial TB and/or TB of the gastrointestinal (GI) tract and/or renal TB.
* Premature infant (born less than 37-weeks gestation) who is less than 3 months of age at Entry.
* Any known contraindication to taking any study drug:

  * Known allergy or intolerance to any of the study drugs or drugs in the same class as the study drugs;
  * Any prohibited medications within three days prior to Entry or planned use within the following 6 months;
  * Unable to take oral medications;
  * Known history of prolonged QT syndrome not caused by electrolyte derangements.
* Received more than 10 days of treatment directed against TB disease within 6 months preceding initiation of study drugs.
* M. tuberculosis isolate known or suspected to be resistant to isoniazid, rifampin, pyrazinamide, ethambutol, and/or fluoroquinolones.
* Known exposure to an infectious adult with drug-resistant TB, including resistance to isoniazid, rifampin, pyrazinamide, ethambutol, and/or fluoroquinolones.
* Has any other documented or suspected clinically significant medical condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
* Previously enrolled in this study.

Late Exclusions:

* M. tuberculosis cultured or detected through World Health Organization (WHO) approved molecular assays (e.g., Cepheid Xpert MTB/RIF, Xpert XDR, sequencing or Hain MTB-DR plus assays) from sputum, swallowed sputum, nasopharyngeal aspirates, stool, or lymph node aspirate obtained around the time of study entry is determined to be resistant to isoniazid and/or rifampin and/or pyrazinamide and/or ethambutol and/or fluoroquinolones.
* Any child with a clinical TB diagnosis who is found to have a definitive alternative diagnosis for their presenting signs and symptoms whose TB treatment is discontinued prior to completion.

Primary outcomes:
measure: TB disease-free survival at 48-weeks
timeFrame: Measured from study entry through week 48
measure: Proportion of participants with grade 3 or higher adverse events over 28 weeks
timeFrame: Measured from study entry through Week 28
Secondary outcomes:
measure: TB disease-free survival at 48-weeks
timeFrame: Measured from study entry through Week 48
measure: TB disease-free survival at 72-weeks
timeFrame: Measured from study entry through Week 72
measure: Adherence to treatment regimens
timeFrame: Measured from study entry through Week 48
measure: Tolerability as assessed by proportion of participants who discontinue treatment
timeFrame: Week 8 (intervention/HPZM) or Week 16 or Week 24 (control/HRZ(E))
measure: Rifapentine Area under the curve (AUC0-24)
timeFrame: Measured from study entry through Week 8
measure: Rifapentine minimal concentration (Cmin)
timeFrame: Measured from study entry through Week 8
measure: Rifapentine peak concentration (Cmax)
timeFrame: Measured from study entry through Week 8
measure: Moxifloxacin AUC0-24
timeFrame: Measured from study entry through Week 8
measure: Moxifloxacin Cmin
timeFrame: Measured from study entry through Week 8
measure: Moxifloxacin Cmax
timeFrame: Measured from study entry through Week 8
measure: Parent/guardian and/or participant reported palatability and acceptability of study regimen
timeFrame: Baseline, Week 4, Week 8 (Regimens 1 and 2) and at Weeks 16 and 24 (Regimen 1 only)
measure: Adherence as assessed by proportion of participants who have taken at least 90% of their doses
timeFrame: Baseline through Week 8 for HPZM, Week 16 for HRZ(E) with non-severe disease, or Week 24 for HRZ(E) with severe disease
measure: Risk Stratification Algorithm
timeFrame: Measured from study entry through Week 48
measure: Cost effectiveness as assessed by the incremental cost-effective ratio (ICER)
timeFrame: Measured from study entry through Week 24
Other outcomes:
measure: Dolutegravir AUC0-24
timeFrame: Measured from study entry through Week 28
measure: Dolutegravir Cmin
timeFrame: Measured from study entry through Week 28
measure: Dolutegravir Cmax
timeFrame: Measured from study entry through Week 28
measure: Proportion of children living with HIV
timeFrame: Week 24 and Week 48
Locations:
city: Chennai
country: India
facility: Indian Council of Medical Research - National Institute for Research in Tuberculosis
city: Pune
country: India
facility: Dr. D.Y. Patil Medical College, Hospital and Research Center
city: Bandung
country: Indonesia
facility: Faculty of Medicine, Universitas Padjadjaran
city: Maputo
country: Mozambique
facility: Instituto Nacional de Saúde (INS)
city: Durban
country: South Africa
facility: Africa Health Research Institute (AHRI)
city: Kampala
country: Uganda
facility: MU-JHU Care Ltd
city: Lusaka
country: Zambia
facility: University of Zambia, School of Medicine
Study officials:
affiliation: Johns Hopkins University
name: Nicole Salazar-Austin, MD, ScM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Avelox package insert. U.S. Food and Drug Administration. (2016). Label: Avelox (moxifloxacin hydrochloride) tablets. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021085s063lbl.pdf
citation: Baciewicz AM, Self TH. Isoniazid interactions. South Med J. 1985 Jun;78(6):714-8. doi: 10.1097/00007611-198506000-00025.
citation: Ball P. Moxifloxacin (Avelox): an 8-methoxyquinolone antibacterial with enhanced potency. Int J Clin Pract. 2000 Jun;54(5):329-32.
citation: Berg A, Clary J, Hanna D, Nuermberger E, Lenaerts A, Ammerman N, Ramey M, Hartley D, Hermann D. Model-Based Meta-Analysis of Relapsing Mouse Model Studies from the Critical Path to Tuberculosis Drug Regimens Initiative Database. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0179321. doi: 10.1128/AAC.01793-21. Epub 2022 Jan 31.
citation: Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, Fujiwara P, Grzemska M, Hopewell PC, Iseman MD, Jasmer RM, Koppaka V, Menzies RI, O'Brien RJ, Reves RR, Reichman LB, Simone PM, Starke JR, Vernon AA; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003 Feb 15;167(4):603-62. doi: 10.1164/rccm.167.4.603. No abstract available.
citation: Burman WJ, Goldberg S, Johnson JL, Muzanye G, Engle M, Mosher AW, Choudhri S, Daley CL, Munsiff SS, Zhao Z, Vernon A, Chaisson RE. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med. 2006 Aug 1;174(3):331-8. doi: 10.1164/rccm.200603-360OC. Epub 2006 May 4.
citation: Centers for Disease Control and Prevention. (2023, March 22). Tuberculosis (TB) Treatment, Treatment for TB Disease. https://www.cdc.gov/tb/topic/treatment/tbdisease.htm
citation: Combs DL, O'Brien RJ, Geiter LJ. USPHS Tuberculosis Short-Course Chemotherapy Trial 21: effectiveness, toxicity, and acceptability. The report of final results. Ann Intern Med. 1990 Mar 15;112(6):397-406. doi: 10.7326/0003-4819-76-3-112-6-397.
citation: Conde MB, Efron A, Loredo C, De Souza GR, Graca NP, Cezar MC, Ram M, Chaudhary MA, Bishai WR, Kritski AL, Chaisson RE. Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial. Lancet. 2009 Apr 4;373(9670):1183-9. doi: 10.1016/S0140-6736(09)60333-0.
citation: Donald PR, Maritz JS, Diacon AH. The pharmacokinetics and pharmacodynamics of rifampicin in adults and children in relation to the dosage recommended for children. Tuberculosis (Edinb). 2011 May;91(3):196-207. doi: 10.1016/j.tube.2011.02.004. Epub 2011 Mar 22.
citation: Dooley KE, Park JG, Swindells S, Allen R, Haas DW, Cramer Y, Aweeka F, Wiggins I, Gupta A, Lizak P, Qasba S, van Heeswijk R, Flexner C; ACTG 5267 Study Team. Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group Study A5267. J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):455-62. doi: 10.1097/QAI.0b013e3182410503.
citation: Dooley KE, Bliven-Sizemore EE, Weiner M, Lu Y, Nuermberger EL, Hubbard WC, Fuchs EJ, Melia MT, Burman WJ, Dorman SE. Safety and pharmacokinetics of escalating daily doses of the antituberculosis drug rifapentine in healthy volunteers. Clin Pharmacol Ther. 2012 May;91(5):881-8. doi: 10.1038/clpt.2011.323.
citation: Dooley KE, Kaplan R, Mwelase N, Grinsztejn B, Ticona E, Lacerda M, Sued O, Belonosova E, Ait-Khaled M, Angelis K, Brown D, Singh R, Talarico CL, Tenorio AR, Keegan MR, Aboud M; International Study of Patients with HIV on Rifampicin ING study group. Dolutegravir-based Antiretroviral Therapy for Patients Coinfected With Tuberculosis and Human Immunodeficiency Virus: A Multicenter, Noncomparative, Open-label, Randomized Trial. Clin Infect Dis. 2020 Feb 3;70(4):549-556. doi: 10.1093/cid/ciz256.
citation: Dorman SE, Goldberg S, Stout JE, Muzanyi G, Johnson JL, Weiner M, Bozeman L, Heilig CM, Feng PJ, Moro R, Narita M, Nahid P, Ray S, Bates E, Haile B, Nuermberger EL, Vernon A, Schluger NW; Tuberculosis Trials Consortium. Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium. J Infect Dis. 2012 Oct 1;206(7):1030-40. doi: 10.1093/infdis/jis461. Epub 2012 Jul 30.
citation: Dorman SE, Savic RM, Goldberg S, Stout JE, Schluger N, Muzanyi G, Johnson JL, Nahid P, Hecker EJ, Heilig CM, Bozeman L, Feng PJ, Moro RN, MacKenzie W, Dooley KE, Nuermberger EL, Vernon A, Weiner M; Tuberculosis Trials Consortium. Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial. Am J Respir Crit Care Med. 2015 Feb 1;191(3):333-43. doi: 10.1164/rccm.201410-1843OC.
citation: Dorman SE, Nahid P, Kurbatova EV, Goldberg SV, Bozeman L, Burman WJ, Chang KC, Chen M, Cotton M, Dooley KE, Engle M, Feng PJ, Fletcher CV, Ha P, Heilig CM, Johnson JL, Lessem E, Metchock B, Miro JM, Nhung NV, Pettit AC, Phillips PPJ, Podany AT, Purfield AE, Robergeau K, Samaneka W, Scott NA, Sizemore E, Vernon A, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group and the Tuberculosis Trials Consortium. High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial. Contemp Clin Trials. 2020 Mar;90:105938. doi: 10.1016/j.cct.2020.105938. Epub 2020 Jan 22.
citation: Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400.
citation: Dossing M, Wilcke JT, Askgaard DS, Nybo B. Liver injury during antituberculosis treatment: an 11-year study. Tuber Lung Dis. 1996 Aug;77(4):335-40. doi: 10.1016/s0962-8479(96)90098-2.
citation: Ellard GA. Absorption, metabolism and excretion of pyrazinamide in man. Tubercle. 1969 Jun;50(2):144-58. doi: 10.1016/0041-3879(69)90020-8. No abstract available.
citation: Ellard GA. The potential clinical significance of the isoniazid acetylator phenotype in the treatment of pulmonary tuberculosis. Tubercle. 1984 Sep;65(3):211-27. doi: 10.1016/0041-3879(84)90079-5. No abstract available.
citation: Ellard GA, Humphries MJ, Gabriel M, Teoh R. Penetration of pyrazinamide into the cerebrospinal fluid in tuberculous meningitis. Br Med J (Clin Res Ed). 1987 Jan 31;294(6567):284-5. doi: 10.1136/bmj.294.6567.284. No abstract available.
citation: Food and Drug Administration (FDA). Guidance on General Clinical Pharmacology Considerations for Pediatric Studies for Drugs and Biological Products: Guidance for Industry (draft guidance) December 2014. [Available from: https://www.fda.gov/media/90358/download.]
citation: Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, Pappas F, Phillips PP, Nunn AJ; REMoxTB Consortium. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1577-87. doi: 10.1056/NEJMoa1407426. Epub 2014 Sep 7.
citation: Griesel R, Hill A, Meintjes G, Maartens G. Standard versus double dose dolutegravir in patients with HIV-associated tuberculosis: a phase 2 non-comparative randomised controlled (RADIANT-TB) trial. Wellcome Open Res. 2021 Jan 11;6:1. doi: 10.12688/wellcomeopenres.16473.1. eCollection 2021.
citation: Griesel R, Zhao Y, Simmons B, Omar Z, Wiesner L, Keene CM, Hill AM, Meintjes G, Maartens G. Standard-dose versus double-dose dolutegravir in HIV-associated tuberculosis in South Africa (RADIANT-TB): a phase 2, non-comparative, randomised controlled trial. Lancet HIV. 2023 Jul;10(7):e433-e441. doi: 10.1016/S2352-3018(23)00081-4. Epub 2023 May 22.
citation: Hibma JE, Radtke KK, Dorman SE, Jindani A, Dooley KE, Weiner M, McIlleron HM, Savic RM. Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection. Am J Respir Crit Care Med. 2020 Sep 15;202(6):866-877. doi: 10.1164/rccm.201912-2489OC.
citation: Hsu AJ, Tamma PD. The Johns Hopkins Hospital Antibiotics Guidelines 2023-2024. Treatment recommendations for hospitalized children. 2022 Johns Hopkins Medicine. Website: https://intranet.insidehopkinsmedicine.org/asp/pediatric.html. Last visited on: October 9th, 2023.
citation: Imperial MZ, Luetkenmeyer A, Dawson R, et al; the ACTG A5372 Protocol Team. DTG PK In People With HIV Receiving Daily 1HP For Latent TB Treatment (ACTG A5372). CROI, Conference on Retroviruses and Opportunistic Infections, 2022, Feb 15. Abstract 78.
citation: Jindani A, Harrison TS, Nunn AJ, Phillips PP, Churchyard GJ, Charalambous S, Hatherill M, Geldenhuys H, McIlleron HM, Zvada SP, Mungofa S, Shah NA, Zizhou S, Magweta L, Shepherd J, Nyirenda S, van Dijk JH, Clouting HE, Coleman D, Bateson AL, McHugh TD, Butcher PD, Mitchison DA; RIFAQUIN Trial Team. High-dose rifapentine with moxifloxacin for pulmonary tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1599-608. doi: 10.1056/NEJMoa1314210.
citation: Kay L, Kampmann JP, Svendsen TL, Vergman B, Hansen JE, Skovsted L, Kristensen M. Influence of rifampicin and isoniazid on the kinetics of phenytoin. Br J Clin Pharmacol. 1985 Oct;20(4):323-6. doi: 10.1111/j.1365-2125.1985.tb05071.x.
citation: Kjellsson MC, Via LE, Goh A, Weiner D, Low KM, Kern S, Pillai G, Barry CE 3rd, Dartois V. Pharmacokinetic evaluation of the penetration of antituberculosis agents in rabbit pulmonary lesions. Antimicrob Agents Chemother. 2012 Jan;56(1):446-57. doi: 10.1128/AAC.05208-11. Epub 2011 Oct 10.
citation: Kohno S, Koga H, Kaku M, Maesaki S, Hara K. Prospective comparative study of ofloxacin or ethambutol for the treatment of pulmonary tuberculosis. Chest. 1992 Dec;102(6):1815-8. doi: 10.1378/chest.102.6.1815.
citation: Lacroix C, Tranvouez JL, Phan Hoang T, Duwoos H, Lafont O. Pharmacokinetics of pyrazinamide and its metabolites in patients with hepatic cirrhotic insufficiency. Arzneimittelforschung. 1990 Jan;40(1):76-9.
citation: Mathad JS, Queiroz ATL, Bhosale R, Alexander M, Naik S, Kulkarni V, Andrade BB, Gupta A. Transcriptional Analysis for Tuberculosis in Pregnant Women From the PRegnancy Associated Changes In Tuberculosis Immunology (PRACHITi) Study. Clin Infect Dis. 2022 Dec 19;75(12):2239-2242. doi: 10.1093/cid/ciac437.
citation: Merle CS, Fielding K, Sow OB, Gninafon M, Lo MB, Mthiyane T, Odhiambo J, Amukoye E, Bah B, Kassa F, N'Diaye A, Rustomjee R, de Jong BC, Horton J, Perronne C, Sismanidis C, Lapujade O, Olliaro PL, Lienhardt C; OFLOTUB/Gatifloxacin for Tuberculosis Project. A four-month gatifloxacin-containing regimen for treating tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1588-98. doi: 10.1056/NEJMoa1315817.
citation: Moro RN, Scott NA, Vernon A, Tepper NK, Goldberg SV, Schwartzman K, Leung CC, Schluger NW, Belknap RW, Chaisson RE, Narita M, Machado ES, Lopez M, Sanchez J, Villarino ME, Sterling TR. Exposure to Latent Tuberculosis Treatment during Pregnancy. The PREVENT TB and the iAdhere Trials. Ann Am Thorac Soc. 2018 May;15(5):570-580. doi: 10.1513/AnnalsATS.201704-326OC.
citation: Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: observations in routine treatment. Tuber Lung Dis. 1996 Feb;77(1):37-42. doi: 10.1016/s0962-8479(96)90073-8.
citation: Bemer-Melchior P, Bryskier A, Drugeon HB. Comparison of the in vitro activities of rifapentine and rifampicin against Mycobacterium tuberculosis complex. J Antimicrob Chemother. 2000 Oct;46(4):571-6. doi: 10.1093/jac/46.4.571.
citation: Patel AM, McKeon J. Avoidance and management of adverse reactions to antituberculosis drugs. Drug Saf. 1995 Jan;12(1):1-25. doi: 10.2165/00002018-199512010-00001.
citation: Patel K, Goldman JL. Safety Concerns Surrounding Quinolone Use in Children. J Clin Pharmacol. 2016 Sep;56(9):1060-75. doi: 10.1002/jcph.715. Epub 2016 Mar 28.
citation: Peloquin CA, Namdar R, Dodge AA, Nix DE. Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids. Int J Tuberc Lung Dis. 1999 Aug;3(8):703-10.
citation: Pierfitte C, Royer RJ. Tendon disorders with fluoroquinolones. Therapie. 1996 Jul-Aug;51(4):419-20. No abstract available.
citation: Prideaux B, Dartois V, Staab D, Weiner DM, Goh A, Via LE, Barry CE 3rd, Stoeckli M. High-sensitivity MALDI-MRM-MS imaging of moxifloxacin distribution in tuberculosis-infected rabbit lungs and granulomatous lesions. Anal Chem. 2011 Mar 15;83(6):2112-8. doi: 10.1021/ac1029049. Epub 2011 Feb 18.
citation: Priftin package insert. National Institute of Allergy and Infectious Diseases. (2021, July). Rifapentine (Priftin) Prescribing Information. National Institute of Allergy and Infectious Diseases.https://rsc.niaid.nih.gov/sites/default/files/Rifapentine%20%28Priftin%29%20PI_dated%20July%202021.pdf
citation: Radtke KK, Hesseling AC, Winckler JL, Draper HR, Solans BP, Thee S, Wiesner L, van der Laan LE, Fourie B, Nielsen J, Schaaf HS, Savic RM, Garcia-Prats AJ. Moxifloxacin Pharmacokinetics, Cardiac Safety, and Dosing for the Treatment of Rifampicin-Resistant Tuberculosis in Children. Clin Infect Dis. 2022 Apr 28;74(8):1372-1381. doi: 10.1093/cid/ciab641.
citation: Reves R, Heilig CM, Tapy JM, Bozeman L, Kyle RP, Hamilton CD, Bock N, Narita M, Wing D, Hershfield E, Goldberg SV; Tuberculosis Trials Consortium. Intermittent tuberculosis treatment for patients with isoniazid intolerance or drug resistance. Int J Tuberc Lung Dis. 2014 May;18(5):571-80. doi: 10.5588/ijtld.13.0304.
citation: Rosenthal IM, Zhang M, Williams KN, Peloquin CA, Tyagi S, Vernon AA, Bishai WR, Chaisson RE, Grosset JH, Nuermberger EL. Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. PLoS Med. 2007 Dec;4(12):e344. doi: 10.1371/journal.pmed.0040344.
citation: Rosenthal IM, Zhang M, Almeida D, Grosset JH, Nuermberger EL. Isoniazid or moxifloxacin in rifapentine-based regimens for experimental tuberculosis? Am J Respir Crit Care Med. 2008 Nov 1;178(9):989-93. doi: 10.1164/rccm.200807-1029OC. Epub 2008 Aug 21.
citation: Rosenthal IM, Tasneen R, Peloquin CA, Zhang M, Almeida D, Mdluli KE, Karakousis PC, Grosset JH, Nuermberger EL. Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis. Antimicrob Agents Chemother. 2012 Aug;56(8):4331-40. doi: 10.1128/AAC.00912-12. Epub 2012 Jun 4.
citation: Rustomjee R, Lienhardt C, Kanyok T, Davies GR, Levin J, Mthiyane T, Reddy C, Sturm AW, Sirgel FA, Allen J, Coleman DJ, Fourie B, Mitchison DA; Gatifloxacin for TB (OFLOTUB) study team. A Phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis. 2008 Feb;12(2):128-38.
citation: Sanofi. Rifadin [rifampin] package insert. Sanofi. 2023, February. URL:https://products.sanofi.us/rifadin/rifadin.pdf.
citation: Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. Eur Respir J. 1996 Oct;9(10):2026-30. doi: 10.1183/09031936.96.09102026.
citation: Seddon JA, Garcia-Prats AJ, Purchase SE, Osman M, Demers AM, Hoddinott G, Crook AM, Owen-Powell E, Thomason MJ, Turkova A, Gibb DM, Fairlie L, Martinson N, Schaaf HS, Hesseling AC. Levofloxacin versus placebo for the prevention of tuberculosis disease in child contacts of multidrug-resistant tuberculosis: study protocol for a phase III cluster randomised controlled trial (TB-CHAMP). Trials. 2018 Dec 20;19(1):693. doi: 10.1186/s13063-018-3070-0.
citation: Segev S, Yaniv I, Haverstock D, Reinhart H. Safety of long-term therapy with ciprofloxacin: data analysis of controlled clinical trials and review. Clin Infect Dis. 1999 Feb;28(2):299-308. doi: 10.1086/515132.
citation: Snider DE Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle. 1980 Dec;61(4):191-6. doi: 10.1016/0041-3879(80)90038-0.
citation: Turkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A, Hissar S, Choo L, Musoke P, Mulenga V, Mave V, Joseph B, LeBeau K, Thomason MJ, Mboizi RB, Kapasa M, van der Zalm MM, Raichur P, Bhavani PK, McIlleron H, Demers AM, Aarnoutse R, Love-Koh J, Seddon JA, Welch SB, Graham SM, Hesseling AC, Gibb DM, Crook AM; SHINE Trial Team. Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children. N Engl J Med. 2022 Mar 10;386(10):911-922. doi: 10.1056/NEJMoa2104535.
citation: Turkova A, Waalewijn H, Chan MK, Bollen PDJ, Bwakura-Dangarembizi MF, Kekitiinwa AR, Cotton MF, Lugemwa A, Variava E, Ahimbisibwe GM, Srirompotong U, Mumbiro V, Amuge P, Zuidewind P, Ali S, Kityo CM, Archary M, Ferrand RA, Violari A, Gibb DM, Burger DM, Ford D, Colbers A; ODYSSEY Trial Team. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e627-e637. doi: 10.1016/S2352-3018(22)00160-6. Epub 2022 Jul 19.
citation: UNAIDS. (2022, March 24). Fact Sheet - Tuberculosis (TB) and HIV. https://www.unaids.org/sites/default/files/media_asset/20220324_TB_FactSheet_en.pdf
citation: Weiner M, Savic RM, Kenzie WR, Wing D, Peloquin CA, Engle M, Bliven E, Prihoda TJ, Gelfond JA, Scott NA, Abdel-Rahman SM, Kearns GL, Burman WJ, Sterling TR, Villarino ME; Tuberculosis Trials Consortium PREVENT TB Pharmacokinetic Group. Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection. J Pediatric Infect Dis Soc. 2014 Jun;3(2):132-45. doi: 10.1093/jpids/pit077. Epub 2014 Jan 16.
citation: Williamson B, Dooley KE, Zhang Y, Back DJ, Owen A. Induction of influx and efflux transporters and cytochrome P450 3A4 in primary human hepatocytes by rifampin, rifabutin, and rifapentine. Antimicrob Agents Chemother. 2013 Dec;57(12):6366-9. doi: 10.1128/AAC.01124-13. Epub 2013 Sep 23.
citation: Wirth S, Emil SGS, Engelis A, Digtyar V, Criollo M, DiCasoli C, Stass H, Willmann S, Nkulikiyinka R, Grossmann U; MOXIPEDIA Study Group. Moxifloxacin in Pediatric Patients With Complicated Intra-abdominal Infections: Results of the MOXIPEDIA Randomized Controlled Study. Pediatr Infect Dis J. 2018 Aug;37(8):e207-e213. doi: 10.1097/INF.0000000000001910.
citation: World Health Organization, Global Tuberculosis Programme, Maternal, Newborn, Child & Adolescent Health & Ageing (2006). Ethambutol efficacy and toxicity: literature review and recommendations for daily and intermittent dosage in children. WHO/HTM/TB/2006.365, WHO/FCH/CAH/2006.3.
citation: World Health Organization (WHO), and UNITAID. Toolkit for research and development of paediatric antiretroviral drugs and formulations. Geneva: World Health Organization; 2018. License: CC BY-NC-SA 3.0 IGO. URL: https://iris.who.int/bitstream/handle/10665/273151/9789241514361-eng.pdf?sequence=1
citation: World Health Organization (2022a) WHO Global Tuberculosis Report 2022. Global Tuberculosis Programme, Tuberculosis Vaccine Accelerator Council. October, 2022. ISBN: 978-92-4-006172-9.
citation: WHO consolidated guidelines on tuberculosis: Module 4: Treatment - Drug-susceptible tuberculosis treatment [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK581329/
citation: WHO consolidated guidelines on tuberculosis: Module 5: Management of tuberculosis in children and adolescents [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK579387/
citation: World Health Organization (2022). Growth reference data for 5-19 years. [April 19, 2022]. Available from: https://www.who.int/tools/growth-reference-data-for-5to19-years.
citation: World Health Organization (2022). Child growth standards. [April 19, 2022]. Available from: https://www.who.int/tools/child-growth-standards.
citation: World Health Organization (2022f). Global Tuberculosis Report 2022; 3.3 TB treatment and treatment coverage. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022/tb-diagnosis-treatment/3-3-tb-treatment-and-treatment-coverage. Last visited: November 1, 2023.
citation: Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003 Jun 1;167(11):1472-7. doi: 10.1164/rccm.200206-626OC. Epub 2003 Jan 31.
citation: Zent C, Smith P. Study of the effect of concomitant food on the bioavailability of rifampicin, isoniazid and pyrazinamide. Tuber Lung Dis. 1995 Apr;76(2):109-13. doi: 10.1016/0962-8479(95)90551-0.
citation: Zhang T, Li SY, Williams KN, Andries K, Nuermberger EL. Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med. 2011 Sep 15;184(6):732-7. doi: 10.1164/rccm.201103-0397OC. Epub 2011 Jun 9.
citation: Zierski M, Bek E. Side-effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis. A controlled clinical study. Tubercle. 1980 Mar;61(1):41-9. doi: 10.1016/0041-3879(80)90060-4.
citation: Zvada SP, Van Der Walt JS, Smith PJ, Fourie PB, Roscigno G, Mitchison D, Simonsson US, McIlleron HM. Effects of four different meal types on the population pharmacokinetics of single-dose rifapentine in healthy male volunteers. Antimicrob Agents Chemother. 2010 Aug;54(8):3390-4. doi: 10.1128/AAC.00345-10. Epub 2010 Jun 1.