- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00130247
Tuberculosis Treatment Shortening Trial
A Prospective Study of Shortening the Duration of Standard Short Course Chemotherapy From 6 Months to 4 Months in HIV-non-infected Patients With Fully Drug-Susceptible, Non-cavitary Pulmonary Tuberculosis With Negative Sputum Cultures After 2 Months of Anti-TB Treatment
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 3
Kontakte und Standorte
Studienorte
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Espírito Santo
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Vitória, Espírito Santo, Brasilien, 29040-091
- Universidade Federal do Espirito Santo - Duke Hubert-Yeargan Center
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National Capital Region
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Makati, National Capital Region, Philippinen, 1229
- Makati Medical Center
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Kampala, Uganda, 99999
- Mulago Hospital Complex
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
-Adults, male or female, aged 18-60. -Newly diagnosed initial episodes of pulmonary tuberculosis. Sputum smear-positive and -negative patients are eligible for enrollment. The diagnosis of tuberculosis must be confirmed by culture. Acid fast bacteria (AFB) smear positive patients found later not to have tuberculosis (TB) (i.e. those with non-tuberculous mycobacterial disease) and those without culture confirmation [at least one culture on solid media growing > 10 colonies of Mycobacterium tuberculosis (MTB) or a positive BACTEC or Mycobacteria growth indicator tube (MGIT) enriched liquid culture growing MTB] will be removed from the study. -Chest X-ray and clinical findings consistent with tuberculosis. -Hemoglobin greater than or equal to 8 gm/dL (greater than or equal to 5.0 mmol/L). -Serum creatinine < 2 mg/dL (< 177 micro mol/L). -Serum aspartate aminotransferase (AST) < 1.5 times the upper limit of normal for the testing laboratory, and serum total bilirubin < 1.3 mg/dL (22.2 micro mol/L). -Random serum glucose less than or equal to 150 mg/dl (8.3 mmol/L). -Ambulatory. -Willing to provide informed consent for study participation, provide required specimens for examination, and to undergo and receive results of human immunodeficiency virus (HIV) testing. -Willing to receive supervised anti-TB treatment. -Completion of the required 112 doses of chemotherapy within 18 weeks of starting treatment.
Exclusion Criteria:
-Human immunodeficiency virus (HIV)-infected. -History of prior tuberculosis or history of previous tuberculosis treatment. -Pregnant or breastfeeding. -Cavitary tuberculosis on initial chest X-ray (taken within 14 days of study entry). -Exposure to person(s) with known drug resistant tuberculosis. -Patients receiving chronic steroids or other immunosuppressive medications. -Extra-pulmonary tuberculosis. -Patients with drug resistant tuberculosis (resistance to isoniazid (INH), rifampicin, pyrazinamide or ethambutol). -Professional sex worker, alcoholic and/or intravenous (IV) drug abuser. -Silicosis or other serious chronic medical problems including diabetes mellitus or chronic renal failure. Final determination of eligibility will be made after review of drug susceptibility testing results on an initial sputum isolate and results of all sputum cultures. Pregnant patients may not be enrolled in the study. Patients in the 4 month arm who become pregnant during months 5 and 6 of study participation will be dropped from the study and receive an additional 2 months of treatment with INH and rifampicin.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: 2EHRZ/2HR arm
Daily treatment with isoniazid (INH), rifampicin, ethambutol and pyrazinamide for 2 months followed by 2 months of daily INH plus rifampicin over a maximum time period of 18 weeks.
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Mycobacteriostatic agent given to prevent emergence of drug resistance to other 1st line drugs; dosages are 15-25 milligram (mg)/ kilogram (kg)/day (d).
Hydrazide of isonicotininc acid; antimicrobial activity is limited to mycobacteria where it inhibits the synthesis of mycolic acids.
1st line bactericidal agent; dosages are 15-30 mg/kg/d, up to 2 grams (gm)/d.
1st line bactericidal agent which inhibits deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase; dosages are 10 mg/kg/d (up to 600 mg/d).
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Aktiver Komparator: 2EHRZ/4HR arm
Daily treatment with Isoniazid (INH), rifampicin, ethambutol and pyrazinamide for 2 months followed by 4 months of daily INH plus rifampicin over a maximum time period of 28 weeks.
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Mycobacteriostatic agent given to prevent emergence of drug resistance to other 1st line drugs; dosages are 15-25 milligram (mg)/ kilogram (kg)/day (d).
Hydrazide of isonicotininc acid; antimicrobial activity is limited to mycobacteria where it inhibits the synthesis of mycolic acids.
1st line bactericidal agent; dosages are 15-30 mg/kg/d, up to 2 grams (gm)/d.
1st line bactericidal agent which inhibits deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase; dosages are 10 mg/kg/d (up to 600 mg/d).
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-tuberculosis (TB) Treatment - Intention-to-treat
Zeitfenster: 30 months
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Patients who presented with TB after completion of study phase treatment but before the end of follow-up were classified as relapses.
A bacteriologic relapse was defined as a patient who became consistently culture-positive [defined as at least 1 of the following]: (a) at least 1 sputum mycobacterial culture growing at least 10 colonies of MTB on solid medium; (b) 2 or more respiratory secretion cultures that are positive for MTB in liquid media; or (c) any culture from an extrapulmonary site that is positive for MTB during follow-up after successful completion of initial anti-TB treatment.
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30 months
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Bacteriologic or Clinical Relapse at 30 Months After Onset of Initial Anti-TB Treatment - Per-protocol
Zeitfenster: 30 months
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Patients who presented with TB after completion of study phase treatment but before the end of follow-up were classified as relapses.
A bacteriologic relapse was defined as a patient who became consistently culture-positive [defined as at least 1 of the following]: (a) at least 1 sputum mycobacterial culture growing at least 10 colonies of MTB on solid medium; (b) 2 or more respiratory secretion cultures that are positive for MTB in liquid media; or (c) any culture from an extrapulmonary site that is positive for MTB during follow-up after successful completion of initial anti-TB treatment.
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30 months
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Intention to Treat
Zeitfenster: 2 years
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A culture-positive treatment failure was defined as initial culture conversion but subsequent reversion to culture positivity.
A clinical treatment failure was defined as a patient with clinical and/or radiographic evidence of progressive tuberculosis not confirmed by a positive culture after 4 or more months of anti-TB treatment while still receiving treatment.
Patients who defaulted before completing study treatment and returned later with culture-positive tuberculosis were termed failures after non-adherence.
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2 years
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Treatment Failures or Relapses at 2 Years After Completion of TB Treatment: Per Protocol
Zeitfenster: 2 years
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A culture-positive treatment failure was defined as initial culture conversion but subsequent reversion to culture positivity.
A clinical treatment failure was defined as a patient with clinical and/or radiographic evidence of progressive tuberculosis not confirmed by a positive culture after 4 or more months of anti-TB treatment while still receiving treatment.
Patients who defaulted before completing study treatment and returned later with culture-positive tuberculosis were termed failures after non-adherence.
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2 years
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Relapses at 1 and 2 Years
Zeitfenster: 1 and 2 years after successful completion of initial anti-TB treatment
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1 and 2 years after successful completion of initial anti-TB treatment
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Acquired Drug Resistance in Patients Who Relapsed
Zeitfenster: 2 years
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2 years
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Immunologic: Changes in Cytokine Levels in Mycobacterium Tubercolosis (MTB) Antigen-stimulated Whole Blood Culture Supernatants - Results Are Pending
Zeitfenster: After 2 and 6 months of anti-TB treatment and upon relapse
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After 2 and 6 months of anti-TB treatment and upon relapse
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Immunologic: Store Peripheral Blood Mononuclear Cells (PBMC) - Results Are Pending
Zeitfenster: Pre-treatment and serum pre-treatment after 2 and 6 months of anti-TB treatment, and at the time of relapse for future immunologic analysis
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Pre-treatment and serum pre-treatment after 2 and 6 months of anti-TB treatment, and at the time of relapse for future immunologic analysis
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Immunologic: Changes in Sputum Cytokine Levels - Results Are Pending
Zeitfenster: After 1 and 2 months of anti-TB treatment
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After 1 and 2 months of anti-TB treatment
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Microbiologic: Changes in Sputum Mycobacterial mRNA - Results Are Pending
Zeitfenster: At 1 and 2 months of anti-TB treatment, and upon relapse
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At 1 and 2 months of anti-TB treatment, and upon relapse
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Microbiologic: Time After Inoculation Until Culture Positive in BACTEC 460 or MGIT 960 Enriched Liquid Media After 2 Months in Treatment - Results Are Pending
Zeitfenster: Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 24, and 30
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Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 24, and 30
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Mitarbeiter und Ermittler
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- Johnson JL, Thiel BA. Time until relapse in tuberculosis treatment trials: implication for phase 3 trial design. Am J Respir Crit Care Med. 2012 Sep 1;186(5):464. doi: 10.1164/ajrccm.186.5.464. No abstract available.
- Palaci M, Dietze R, Hadad DJ, Ribeiro FK, Peres RL, Vinhas SA, Maciel EL, do Valle Dettoni V, Horter L, Boom WH, Johnson JL, Eisenach KD. Cavitary disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J Clin Microbiol. 2007 Dec;45(12):4064-6. doi: 10.1128/JCM.01780-07. Epub 2007 Oct 10.
- Bark CM, Dietze R, Okwera A, Quelapio MI, Thiel BA, Johnson JL. Clinical symptoms and microbiological outcomes in tuberculosis treatment trials. Tuberculosis (Edinb). 2011 Nov;91(6):601-4. doi: 10.1016/j.tube.2011.05.007. Epub 2011 Aug 2.
- Colangeli R, Jedrey H, Kim S, Connell R, Ma S, Chippada Venkata UD, Chakravorty S, Gupta A, Sizemore EE, Diem L, Sherman DR, Okwera A, Dietze R, Boom WH, Johnson JL, Mac Kenzie WR, Alland D; DMID 01-009/Tuberculosis Trials Consortium Study 22 Teams. Bacterial Factors That Predict Relapse after Tuberculosis Therapy. N Engl J Med. 2018 Aug 30;379(9):823-833. doi: 10.1056/NEJMoa1715849.
- Bark CM, Thiel BA, Johnson JL. Pretreatment time to detection of Mycobacterium tuberculosis in liquid culture is associated with relapse after therapy. J Clin Microbiol. 2012 Feb;50(2):538. doi: 10.1128/JCM.06193-11. Epub 2011 Nov 23. No abstract available.
- Johnson JL, Hadad DJ, Dietze R, Maciel EL, Sewali B, Gitta P, Okwera A, Mugerwa RD, Alcaneses MR, Quelapio MI, Tupasi TE, Horter L, Debanne SM, Eisenach KD, Boom WH. Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion. Am J Respir Crit Care Med. 2009 Sep 15;180(6):558-63. doi: 10.1164/rccm.200904-0536OC. Epub 2009 Jun 19.
- Maciel EL, Brioschi AP, Peres RL, Guidoni LM, Ribeiro FK, Hadad DJ, Vinhas SA, Zandonade E, Palaci M, Dietze R, Johnson JL. Smoking and 2-month culture conversion during anti-tuberculosis treatment. Int J Tuberc Lung Dis. 2013 Feb;17(2):225-8. doi: 10.5588/ijtld.12.0426.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Infektionen
- Bakterielle Infektionen
- Bakterielle Infektionen und Mykosen
- Grampositive bakterielle Infektionen
- Actinomycetales-Infektionen
- Mycobacterium-Infektionen
- Tuberkulose
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Inhibitoren der Nukleinsäuresynthese
- Enzym-Inhibitoren
- Antimetaboliten
- Hypolipidämische Mittel
- Lipidregulierende Mittel
- Antibakterielle Mittel
- Leprostatische Mittel
- Cytochrom P-450-Enzyminduktoren
- Cytochrom P-450 CYP3A-Induktoren
- Antituberkulöse Mittel
- Antibiotika, Antituberkulose
- Cytochrom P-450 CYP2B6-Induktoren
- Cytochrom P-450 CYP2C8-Induktoren
- Cytochrom P-450 CYP2C19-Induktoren
- Cytochrom P-450 CYP2C9-Induktoren
- Inhibitoren der Fettsäuresynthese
- Rifampin
- Isoniazid
- Pyrazinamid
- Ethambutol
Andere Studien-ID-Nummern
- 01-009
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Produkt, das in den USA hergestellt und aus den USA exportiert wird
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