Evaluation of Antifungal Prophylaxis on Graft-versus-host Disease (GVHD) Patients (ITRAG)
Evaluation of Antifungal Prophylaxis Against Invasive Fungal Infections During Corticosteroid Containing Therapy for Graft-versus-host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Eligible patients who provided an informed consent form will be administered itraconazole oral solution (200mg bid initially, swash and swallow) in either an in patient or outpatient setting. Treatment can be initiated at the same time of or within 10 days after starting systemic immunosuppressive therapy.
Itraconazole oral solution dose can be adjusted according to the liver function test: 1) in case of - AST/ALT level 5-10 times UNL or bilirubin/ALP level 2-5 times UNL, itraconazole dose can be reduced to half (i.e. itraconazole 200mg po once daily or 100mg bid); 2) in case of - AST/ALT level > 10 times UNL or bilirubin/ALP level > 5 times UNL, itraconazole can be stopped.
GVHD treatment can be given per center's policy: With respect to acute GVHD, prednisone (1-2mg/Kg/day) oral or iv can be given on top of calcineurin inhibitor (CNI) GVHD prophylaxis. For chronic GVHD, various type of frontline regimen can be permitted including CNI+prednisone (PD), PD alone, CNI+PD+mycophenolate mofetil (MMF), or MMF+PD. Various dose of PD will be accepted if it is at least from 0.5mg/Kg/day. For example, at SMC, in case of mild grade cGVHD with high risk feature, or of moderate grade cGVHD, CNI plus PD, 0.5mg/kg/day can be given initially. In case of severe grade cGVHD, CNI plus PD, 1.0mg/Kg/day will be given.
Itraconazole will be maintained until PD is tapered to 10mg/day in case of PD alone therapy group, or until PD is stopped in case of CNI+PD or CNI+PD+MMF or MMF+PD group, etc. In addition, patients will receive itraconazole oral suspension until: 1) Development of proven or probable IFIs, 2) Severe toxicity (such as liver function abnormality - AST/ALT level > 10 times UNL or bilirubin/ALP level > 5 times UNL, 3) Worsening GVHD that requires second line therapy for steroid refractory GVHD (in this situation, investigator could stop itraconazole oral solution if there is a potential drug interaction between itraconazole oral solution and 2nd line GVHD drug or prolonged use of itraconazole oral solution could be hazardous to the patient), 4) Need to switch antifungal agent for the treatment of prolonged febrile episode related to systemic infection, thus requiring systemic antifungal treatment, 6) Withdrawal from study participation (patient's decision), or 7) Death.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 4
Contactos e Locais
Locais de estudo
-
-
-
Incheon, Republica da Coréia
- Inha University Hospital
-
Incheon, Republica da Coréia
- Gachon University Gil Hospital
-
Pusan, Republica da Coréia
- Inje University Pusan Paik Hospital
-
Seoul, Republica da Coréia
- Seoul National University Hospital
-
Seoul, Republica da Coréia, 135-710
- Samsung Medical Center
-
Seoul, Republica da Coréia
- Chung-Ang University Hospital
-
Seoul, Republica da Coréia
- Soonchunhyang University Seoul Hospital
-
-
Jeollanam-do
-
Hwasun, Jeollanam-do, Republica da Coréia
- Chonnam National University Hwasun Hospital
-
-
Kyounggi-do
-
Bucheon, Kyounggi-do, Republica da Coréia
- Soonchunhyang University Bucheon Hospital
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
Patients developing or developed acute or chronic GVHD within the last 10 days which require systemic immunosuppressive therapy of corticosteroids with- or-without other immunosuppressive agents including calcineurin inhibitors.
- acute GVHD, grade 2-4
- chronic GVHD, mild grade with high risk or moderate to severe grade
- Written informed consent form
Exclusion Criteria:
- Aspartate transaminase or alanine transaminase level > 10 times UNL or Bilirubin or alkaline phosphatase level > 5 times UNL
- Active or chronic hepatitis virus B or C infection requiring antiviral therapy
- Estimated life expectancy < 30 days
- History of allergy, sensitivity, or any serious reaction to itraconazole oral solution
- Previous history of Zygomycosis
- Evidence of active fungal disease including high galactomannan titer above 0.5, within 2 weeks.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: itraconazole, prophylaxis, Oral solution
For GVHD patients who are required systemic glucocorticoids therapy, itraconazole oral solution will be administered at a dose of 200mg every 12 hours.
|
200mg bid, oral solution, until a dose of prednisone was tapered to 10mg/day in case of prednisone alone therapy group, or until prednisone was stopped in case of CNIs plus prednisone, CNIs plus prednisone plus mycophenolate mofetil, or mycophenolate mofetil plus prednisone group, etc.
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
|---|---|
|
incidence of proven or probable invasive fungal infections
Prazo: at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis.
|
at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis.
|
Medidas de resultados secundários
Medida de resultado |
Prazo |
|---|---|
|
safety profiles of itraconazole oral solution
Prazo: during GVHD treatment with corticosteroids containing regimen
|
during GVHD treatment with corticosteroids containing regimen
|
|
GVHD-specific survival (GSS) of patients receiving corticosteroids based GVHD treatment together with antifungal prophylaxis with itraconazole oral solution
Prazo: from the onset of acute or chronic GVHD to death due to GVHD itself or GVHD-related complications
|
from the onset of acute or chronic GVHD to death due to GVHD itself or GVHD-related complications
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Dong Hwan Kim, M.D./Ph.D., Division of Hematology/Oncology, Department of Medicine
Publicações e links úteis
Publicações Gerais
- Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF; Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008 Feb 1;46(3):327-60. doi: 10.1086/525258. No abstract available.
- Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, Shadduck RK, Shea TC, Stiff P, Friedman DJ, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992 Mar 26;326(13):845-51. doi: 10.1056/NEJM199203263261301.
- Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL, Leitz GJ, Territo MC. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med. 2003 May 6;138(9):705-13. doi: 10.7326/0003-4819-138-9-200305060-00006.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Infecções
- Doenças do sistema imunológico
- Infecções Bacterianas e Micoses
- Micoses
- Infecções Fúngicas Invasivas
- Doença do Enxerto x Hospedeiro
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Anti-Infecciosos
- Inibidores Enzimáticos
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Inibidores do citocromo P-450 CYP3A
- Inibidores da enzima citocromo P-450
- Antagonistas Hormonais
- Antifúngicos
- Inibidores da Síntese de Esteróides
- Inibidores de 14-alfa desmetilase
- Itraconazol
Outros números de identificação do estudo
- 2009-08-099
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
produto fabricado e exportado dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .