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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

Primary Purpose

Hematological Diseases, Allogeneic Stem Cell Transplantation

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

itraconazole

About this trial

This is an interventional prevention trial for Hematological Diseases focused on measuring primary prophylaxis, itraconazole, stem cell transplantation

Eligibility Criteria

14 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Guangzhou General Hospital of Guangzhou Military CommandRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

long-term group

short term group

Arm Description

long-term group refers to prophylaxis by using itraconazole for up to 90 days

short term group refers to prophylaxis by itraconazole for 30 days

Outcomes

Primary Outcome Measures

efficacy evaluation

the success rate of prophylaxis therapy by itraconazole

Secondary Outcome Measures

group difference evaluation

efficacy difference between long-term and short-term groups per success rate at day 90

Full Information

NCT ID

NCT01160952

First Posted

July 12, 2010

Last Updated

July 23, 2010

Sponsor

Guangzhou General Hospital of Guangzhou Military Command

Collaborators

Nanfang Hospital, Southern Medical University, First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Renmin Hospital of Zhongshan Guangdong, Zhujiang Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01160952

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2010

Overall Recruitment Status

Unknown status

Study Start Date

May 2009 (undefined)

Primary Completion Date

December 2010 (Anticipated)

Study Completion Date

March 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Guangzhou General Hospital of Guangzhou Military Command

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematological Diseases, Allogeneic Stem Cell Transplantation

Keywords

primary prophylaxis, itraconazole, stem cell transplantation

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

long-term group

Arm Type

Other

Arm Description

long-term group refers to prophylaxis by using itraconazole for up to 90 days

Arm Title

short term group

Arm Type

Other

Arm Description

short term group refers to prophylaxis by itraconazole for 30 days

Intervention Type

Drug

Intervention Name(s)

itraconazole

Intervention Description

the two groups are defined by different treatment duration

Primary Outcome Measure Information:

Title

efficacy evaluation

Description

the success rate of prophylaxis therapy by itraconazole

Time Frame

90 days

Secondary Outcome Measure Information:

Title

group difference evaluation

Description

efficacy difference between long-term and short-term groups per success rate at day 90

Time Frame

90 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yonghua Li, MD

Phone

8613751880527

lyhood@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Xiaohui Zeng, Pharm D

Phone

8613560327666

gzlcyljd@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yang Xiao, MD

Organizational Affiliation

Guangzhou General Hospital of Guangzhou Military Command

Official's Role

Principal Investigator

Facility Information:

Facility Name

Guangzhou General Hospital of Guangzhou Military Command

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510010

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yonghua Li, MD

Phone

8613751880527

lyhood@163.com

First Name & Middle Initial & Last Name & Degree

Xiaohui Zeng, Pharm D

Phone

8613560327666

gzlcyljd@163.com

First Name & Middle Initial & Last Name & Degree

Yang Xiao, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

14525770

Citation

Marr KA, Crippa F, Leisenring W, Hoyle M, Boeckh M, Balajee SA, Nichols WG, Musher B, Corey L. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood. 2004 Feb 15;103(4):1527-33. doi: 10.1182/blood-2003-08-2644. Epub 2003 Oct 2.

Results Reference

background

PubMed Identifier

12729424

Citation

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.

Results Reference

background

Citation

Chinese guideline for the diagnosis and management of IFI in patients with hematologic/maliglant tumor (revised). Chinese journal of internal medicine 2007，46(7):607-610.

Results Reference

background

PubMed Identifier

24593273

Citation

Lin R, Xu X, Li Y, Sun J, Fan Z, Jiang Q, Huang F, Zhou H, Nie D, Guo Z, Mao Y, Xiao Y, Liu Q. Comparison of long-term and short-term administration of itraconazole for primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation: a multicenter, randomized, open-label trial. Transpl Infect Dis. 2014 Apr;16(2):286-94. doi: 10.1111/tid.12192. Epub 2014 Mar 5.

Results Reference

derived

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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

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