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
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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 di studio
Iscrizione (Effettivo)
Fase
- Fase 4
Contatti e Sedi
Luoghi di studio
-
-
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Incheon, Corea, Repubblica di
- Inha University Hospital
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Incheon, Corea, Repubblica di
- Gachon University Gil Hospital
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Pusan, Corea, Repubblica di
- Inje University Pusan Paik Hospital
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Seoul, Corea, Repubblica di
- Seoul National University Hospital
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Seoul, Corea, Repubblica di, 135-710
- Samsung Medical Center
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Seoul, Corea, Repubblica di
- Chung-Ang University Hospital
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Seoul, Corea, Repubblica di
- Soonchunhyang University Seoul Hospital
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-
Jeollanam-do
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Hwasun, Jeollanam-do, Corea, Repubblica di
- Chonnam National University Hwasun Hospital
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Kyounggi-do
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Bucheon, Kyounggi-do, Corea, Repubblica di
- Soonchunhyang University Bucheon Hospital
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-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Prevenzione
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: 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.
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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.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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incidence of proven or probable invasive fungal infections
Lasso di tempo: at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis.
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at day 100 after starting graft-versus-host disease (GVHD) treatment with corticosteroids based regimen in adjunction to itraconazole oral solution antifungal prophylaxis.
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Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
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safety profiles of itraconazole oral solution
Lasso di tempo: during GVHD treatment with corticosteroids containing regimen
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during GVHD treatment with corticosteroids containing regimen
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GVHD-specific survival (GSS) of patients receiving corticosteroids based GVHD treatment together with antifungal prophylaxis with itraconazole oral solution
Lasso di tempo: from the onset of acute or chronic GVHD to death due to GVHD itself or GVHD-related complications
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from the onset of acute or chronic GVHD to death due to GVHD itself or GVHD-related complications
|
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Dong Hwan Kim, M.D./Ph.D., Division of Hematology/Oncology, Department of Medicine
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Infezioni
- Malattie del sistema immunitario
- Infezioni batteriche e micosi
- Micosi
- Infezioni fungine invasive
- Malattia del trapianto contro l'ospite
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Inibitori enzimatici
- Ormoni, sostituti ormonali e antagonisti ormonali
- Inibitori del citocromo P-450 CYP3A
- Inibitori dell'enzima del citocromo P-450
- Antagonisti ormonali
- Agenti antimicotici
- Inibitori della sintesi di steroidi
- Inibitori della 14-alfa demetilasi
- Itraconazolo
Altri numeri di identificazione dello studio
- 2009-08-099
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
prodotto fabbricato ed esportato dagli Stati Uniti
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