Study of Safety and Efficacy of Different Regimes of Reintroduction of Anti-TB Drugs in Anti-TB Drugs Induced Liver Damage
14 de febrero de 2012 actualizado por: S.K.SHARMA, All India Institute of Medical Sciences, New Delhi
Study of Safety and Efficacy of Different Regimes of Reintroduction of Anti-TB Drugs in Antituberculosis Treatment Induced Hepatotoxicity
Purpose of the study is to evaluate the safety and efficacy of different re-introduction regimens in anti-TB drug induced liver damage.
There is no consensus how best to treat such patients who developed drug induced liver damage.
Descripción general del estudio
Estado
Terminado
Condiciones
Descripción detallada
Tuberculosis continues to be a major health problem in both the developing and developed countries because of its resurgence in the immunosuppressed patients. Short course chemotherapy containing isoniazid, rifampicin and pyrazinamide has proved to be highly effective in the treatment of tuberculosis. One of its adverse effect is liver damage which is the most common side effect leading to interruption of therapy.
There is lack of consensus guidelines for treatment of anti-TB drug induced liver damage Whether the re-introduction should take place with all the drugs given together in full doses (which reduces the chance of resistance and cost to the patient) or in a phased manner. There is lack of studies which compared different regimens of re-introduction of anti-TB drugs.
In this study, we will study three regimes of re-introduction of hepatotoxic anti-tuberculosis drugs (Rifampicin, Isoniazide, Pyrazinamide). These are potent anti-tuberculosis medications and need to be restarted in patients who developed liver toxicities attributed to these medications and became normal when these medicines were stopped. At the time of re-introduction the patients will be randomized in 3 groups.
- First group will receive Isoniazide(5mg/kg/day), Rifampicin(10mg/kg/day) and Pyrazinamide(25mg/kg/day) in full doses on day 1 and continued further.
- second group will receive Rifampicin(10mg/kg/day) in full dose on day 1 and continued, Isoniazide(5mg/kg/day)in full dose on day 8 and continued, Pyrazinamide(25mg/kg/day)on day 15 and continued.
- Third group will receive 100 mg/day of Isoniazide on day 1 which is gradually increased to maximum dose (5mg/kg/day) by day 4 and continued. Rifampicin is introduced on day 8 in a dose of 150 mg/day which is gradually increased to maximum dose (10mg/kg/day) by day 11 and continued. Pyrazinamide is introduced on day 15 in a dose of 500mg/day which is gradually increased to maximum dose (25mg/kg/day) by day 18 and continued.
All the three groups will be monitored for three months by analyzing weekly liver function tests. Any difference in the morbidity, deranged liver function or any other adverse effects will be monitored and treated appropriately.
Tipo de estudio
Intervencionista
Inscripción (Actual)
175
Fase
- Fase 4
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Andhra Pradesh
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Tirupati, Andhra Pradesh, India, 517507
- Sri Venkateswara Institute of Medical Sciences
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Delhi
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New Delhi, Delhi, India, 110029
- All India Institute of Medical Sciences
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
16 años a 65 años (Niño, Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- A rise of five times the upper limit of the normal levels (50 IU/L) of serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)
- A rise in the level of serum total bilirubin level > 1.5mg/dl
- Any increase in serum AST and or ALT above pretreatment values together with anorexia, nausea, vomiting and jaundice
- Absence of serological evidence of infection with hepatitis viruses A,B,C,or E
- Normalization of liver function tests after withdrawal of antituberculosis drugs For diagnosis of anti-TB drugs induced hepatitis, criteria 1 or 2 or 3 should be present along with criteria 4 and 5.
Exclusion Criteria:
- Patients with serological evidence of acute viral hepatitis A,B,C,or E and carriers for HBV & HCV
- Age < 15 year and age > 65 years
- HIV positive patients
- Presence of chronic liver disease or cirrhosis
- Co-administration of other potential hepatotoxic drugs (methotrexate, phenytoin, valproate)
- Chronic alcoholics who consume > 48 g of alcohol/day for at least one year
- Pregnant women
- Subjects not giving consent
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Otro: Arm 1
Arm 1: will receive Isoniazide(5mg/kg/day), Rifampicin(10mg/kg/day) and Pyrazinamide(25mg/kg/day) in full doses on day 1 and continued further
|
Patients who develop ATT drug induced hepatotoxicity will be divided into 3 arms .Arm 1,2,3 will be given drugs as described in detailed description of the title.
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Otro: Arm 2
Arm 2 : will receive Rifampicin(10mg/kg/day) in full dose on day 1 and continued, Isoniazide(5mg/kg/day)in full dose on day 8 and continued, Pyrazinamide(25mg/kg/day)on day 15 and continued
|
Patients who develop ATT drug induced hepatotoxicity will be divided into 3 arms .Arm 1,2,3 will be given drugs as described in detailed description of the title.
|
|
Otro: Arm 3
Arm 3 will receive 100 mg/day of Isoniazide on day 1 which is gradually increased to maximum dose (5mg/kg/day) by day 4 and continued.
Rifampicin is introduced on day 8 in a dose of 150 mg/day which is gradually increased to maximum dose (10mg/kg/day) by day 11 and continued.
Pyrazinamide is introduced on day 15 in a dose of 500mg/day which is gradually increased to maximum dose (25mg/kg/day) by day 18 and continued.
|
Patients who develop ATT drug induced hepatotoxicity will be divided into 3 arms .Arm 1,2,3 will be given drugs as described in detailed description of the title.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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To compare the safety of different regimens of re-introduction of anti-TB drugs in drug induced liver damage.
Periodo de tiempo: 24 months
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24 months
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Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
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To study the predictors of recurrence of drug induced liver damage
Periodo de tiempo: 24 months
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24 months
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To study the risk factors for development of drug induced liver injury
Periodo de tiempo: 24 months
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24 months
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Tahaoglu K, Atac G, Sevim T, Tarun T, Yazicioglu O, Horzum G, Gemci I, Ongel A, Kapakli N, Aksoy E. The management of anti-tuberculosis drug-induced hepatotoxicity. Int J Tuberc Lung Dis. 2001 Jan;5(1):65-9.
- Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med. 2002 Oct 1;166(7):916-9. doi: 10.1164/rccm.2108091.
- Singh J, Garg PK, Tandon RK. Hepatotoxicity due to antituberculosis therapy. Clinical profile and reintroduction of therapy. J Clin Gastroenterol. 1996 Apr;22(3):211-4. doi: 10.1097/00004836-199604000-00012.
- Singh J, Arora A, Garg PK, Thakur VS, Pande JN, Tandon RK. Antituberculosis treatment-induced hepatotoxicity: role of predictive factors. Postgrad Med J. 1995 Jun;71(836):359-62. doi: 10.1136/pgmj.71.836.359.
- Sharma SK. Antituberculosis drugs and hepatotoxicity. Infect Genet Evol. 2004 Jun;4(2):167-70. doi: 10.1016/j.meegid.2003.01.001. No abstract available.
- Sharma SK, Singla R, Sarda P, Mohan A, Makharia G, Jayaswal A, Sreenivas V, Singh S. Safety of 3 different reintroduction regimens of antituberculosis drugs after development of antituberculosis treatment-induced hepatotoxicity. Clin Infect Dis. 2010 Mar 15;50(6):833-9. doi: 10.1086/650576.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de diciembre de 2006
Finalización primaria (Actual)
1 de junio de 2008
Finalización del estudio (Actual)
1 de diciembre de 2008
Fechas de registro del estudio
Enviado por primera vez
27 de noviembre de 2006
Primero enviado que cumplió con los criterios de control de calidad
29 de noviembre de 2006
Publicado por primera vez (Estimar)
30 de noviembre de 2006
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
16 de febrero de 2012
Última actualización enviada que cumplió con los criterios de control de calidad
14 de febrero de 2012
Última verificación
1 de febrero de 2012
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Infecciones
- Infecciones bacterianas
- Infecciones bacterianas y micosis
- Infecciones por bacterias grampositivas
- Infecciones por Actinomycetales
- Infecciones por micobacterias
- Tuberculosis
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes antibacterianos
- Agentes leprostáticos
- Inductores de enzimas de citocromo P-450
- Inductores de citocromo P-450 CYP3A
- Agentes antituberculosos
- Antibióticos, Antituberculosos
- Inductores de citocromo P-450 CYP2B6
- Inductores de citocromo P-450 CYP2C8
- Inductores del citocromo P-450 CYP2C19
- Inductores de citocromo P-450 CYP2C9
- Rifampicina
- Pirazinamida
Otros números de identificación del estudio
- AIIMS/MED/2006/10
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