Long-term Versus Short-term Sequential Therapy (Intravenous Itraconazole Followed by Oral Solution) of Itraconazole as Primary Prophylaxis in Patients Undergoing Allogeneic Stem Cell Transplantation

Phase 2

• Conditions: Hematological Diseases; Allogeneic Stem Cell Transplantation
• Interventions: Drug: itraconazole

• Registration Number: NCT01160952
• Lead Sponsor: Guangzhou General Hospital of Guangzhou Military Command

Brief Summary

* The primary objective of this study is to evaluate the efficacy and safety profile of itraconazole as in primary prophylaxis

* The second objective of this study is to find the difference between long-term versus short-term sequential therapy of Itraconazole (intravenous followed by oral itraconazole) as primary prophylaxis of invasive fungal infections (IFI) in patients undergoing allogeneic stem cell transplantation (allo-SCT)

* also to explore the relationship between the incidence of IFI with plasma concentrations of itraconazole and hydroxy-itraconazole

Detailed Description

Invasive fungal infections (IFI) remain the major cause of death among neutropenic patients receiving high dose chemotherapy or allo-SCT. Especially, patients undergoing allo-SCT generally receive intensive immunosuppressive therapy, which make those patients at high risk of developing IFI.

Prompt intensive antifungal therapy may increase the incidence rate of IFI and improved responses and survival. Antifungal prophylaxis has been recommended in patients undergoing allo-SCT by Infectious diseases society of America (IDSA) and Chinese guidelines for the diagnosis and management of IFI in patients with hematologic/malignant tumor (revised).

Few studies have addressed the role of previous IFI in the feasibility of stem cell transplant, or the secondary prophylaxis with antifungal drugs in preventing recurrence of infection after transplantation. However, given the lack of prospective studies, the role of primary antifungal prevention and the course of treatment remain unclear.

Itraconazole is a wide-spectrum triazole antifungal agent active against Candida albicans, non-albicans, Aspergillus spp., Blastomyces dermatitidis, Blastomyces coccidioides, Cryptococcus neoformans, Sporothrix schenkii, Paracoccidioides brasiliensis, Histoplasma spp. and various kinds of yeast fungi and mycetes.

The role of itraconazole in IFI prophylaxis has been proved by many interventional studies. However the optimal course of prophylaxis is still unknown，especially in China. In this prospective, multicentric study of primary antifungal prevention, long-term or short-term sequential therapy (intravenous followed by oral itraconazole) will be given at standard dose to patients undergoing allogeneic stem cell transplantation to assess the efficacy and safety of itraconazole in primary prophylaxis, and to analysis the relationship between the incidence rate of IFI with plasma concentrations of itraconazole and hydroxy-itraconazole.

Study Timeline

• Study Start: 2009-05
• Status Verified: 2010-07
• Study First Submitted: 2010-07-12
• Study First Submitted QC: 2010-07-12
• Study First Posted: 2010-07-13
• Last Update Submitted: 2010-07-23
• Last Update Posted: 2010-07-26
• Primary Completion: 2010-12
• Study Completion: 2011-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Man or woman between 14 and 60 years of age, inclusive
• Patients who affected by hematological diseases, receiving allo-SCT
• Patients with no previous proven or probable invasive fungal infections. Patients without microbiological evidence but with effective anti-fungal therapy history are inclusive
• Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria

• Currently taking the contra-indicated medications such as teldane, astemizol, cisapride and HMG-CoA reductase inhibitor（e.g. Simvastatin, lovastatin, oral Midazolam and Triazolam）
• History of allergy or intolerance to imidazole or azoles anti-fungal agents (e.g. Fluconazol, Itraconazole, Ketoconazole, Miconazole, Clotrimazole)
• Pregnant women, lactating women or women of child bearing potential without applying valid contraceptive measures
• Patients with current cardiac dysfunction (especially with congestive heart failure) or with the history of congestive heart failure
• Patients with severe liver dysfunction (aminotransferase levels >= 5 times the upper limit of normal and total bilirubin level >= 3mg/dL(51.3 μmol/L); or the severity of liver dysfunction does not match this criteria but the patient is in bad condition and not suitable for this trial( doctors make the decision);
• Patients with renal insufficiency having serum Ccr level <30ml/min, calculated from the following formula:

Male: Ccr (ml/min)=(140-age)×weight (kg) /(0.8136×Crea (μmol/L) ) Female:Ccr (ml/min)=(140-age)×weight (kg) ×0.85/(0.8136× Crea (μmol/L) )

• Patients received any experimental drug within 14 days before the planned start of treatment.
• Patients with bad whole body status and not suitable for the trial (doctors make the decision)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
short term group	itraconazole	short term group refers to prophylaxis by itraconazole for 30 days
long-term group	itraconazole	long-term group refers to prophylaxis by using itraconazole for up to 90 days

Primary Outcome Measures

Name	Time	Method
efficacy evaluation	90 days	the success rate of prophylaxis therapy by itraconazole

Secondary Outcome Measures

Name	Time	Method
group difference evaluation	90 days	efficacy difference between long-term and short-term groups per success rate at day 90

Trial Locations

Locations (1)

Guangzhou General Hospital of Guangzhou Military Command; 🇨🇳 Guangzhou, Guangdong, China