Efficacy, Safety and Serum Concentration of Posaconazole Tablets for Prevention of Pulmonary Fungal Infections in Patients With Hematopoietic Stem Cell Transplantation: An Open, Prospective, Observational, Multicenter Cohort Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 360
- Locations
- 4
- Primary Endpoint
- UGT1A4*3 genotype and plasma concentration of posaconazole
Study Overview
Brief Summary
This open, prospective, observational multicenter cohort study aims to evaluate the efficacy, safety as well as the effective serum concentration of Posaconazole for prevention of pulmonary fungal infections in patients with hematopoietic stem cell transplantation. The correlation of UGT1A4*3 genotype and Cmin of Posaconazole, as well as invasive fungal disease (IFD) breakthrough rates will be utilized to evaluate the efficacy while the safety of Posaconazole will be assessed by the overall incidence and severity of adverse events in patients.
Detailed Description
This open, prospective, observational multicenter cohort study aims to study the efficacy, safety and effective concentration of Posaconazole tablets for prevention of pulmonary fungal infection in patients with hematopoietic stem cell transplantation. A total of 360 hematopoietic stem cell transplantation patients receiving Posaconazole tablets are expected to be enrolled. Posaconazole tablets will be taken orally from the day of transplantation (300 mg Q12h D1) followed by 300 mg Qd, until 90 days after transplantation. The total duration of the study is estimated to be 24 months, with each patient participating for an estimated 3 months. The relationships between UGT1A4*3 genotype and drug serum concentration, IFD incidence, Aspergillus infection rate, IFD-related mortality rate, IFD-free survival rate, and overall survival rate will be used to evaluate the effectiveness of Posaconazole tablets in preventing invasive pulmonary fungal infection in patients with hematopoietic stem cell transplantation. Safety of Posaconazole tablet will be validated by the overall incidence and severity of adverse events in patients.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 13 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 13 years old
- •The primary causes of hematopoietic stem cell transplantation include aplastic anemia, acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, or other hematologic diseases in patients pretreated for hematopoietic stem cell transplantation. The types of transplantation include autologous transplantation, syngeneic transplantation, matched sibling donor transplantation, unrelated donor transplantation and haploidentical transplantation
- •The patients themselves or their authorized clients agree to participate in the clinical study and sign the informed consent
Exclusion Criteria
- •Those with evidence of active fungal infection within 3 weeks prior to enrollment
- •Allergic to azole drugs
- •Severe abnormal liver function
- •Rifampicin, isoniazid, phenytoin, carbamazepine, and long-acting barbiturates were used in combination during the study
- •Any predictably increased patient risk or other factors that might interfere with the outcome of a clinical trial
Outcomes
Primary Outcomes
UGT1A4*3 genotype and plasma concentration of posaconazole
Time Frame: From day 0 to day 22
Blood samples were drawn at baseline (day 0) for analysis of patients' UGT1A4\*3 genotypes and assigned to homozygous, wild-type, and heterozygous genotypes. For posaconazole serum concentrations, blood samples were collected at day 0, 4, 8, 15 and 22.
Secondary Outcomes
- Measurement and record of duration of neutropenia(Duration of 90-day posaconazole prophylaxis)
- The influence of other combined medications for posaconazole plasma concentrations(Duration of 90-day posaconazole prophylaxis)
- Measurement and record of neutrophil counts(Duration of 90-day posaconazole prophylaxis)
- Plasma concentration of the patients who received different dosages of posaconazole as prophylaxis at different time points(Day 0, 4, 8, 15 and 22)
- Effect of GVHD grading on absorption and utilization of posaconazole tablets (plasma concentration)(Duration of 90-day posaconazole prophylaxis)
- Effect of diarrhea on absorption and utilization of posaconazole tablets (plasma concentration)(Duration of 90-day posaconazole prophylaxis)
- Number/Proportion of patients with immunosuppressive agent application and adjustments(Duration of 90-day posaconazole prophylaxis)
- The incidence of invasive fungal disease (IFD) and the incidence of Aspergillus infection(90 days posaconazole prophylaxis and 7 days after prophylaxis ending)
- Adverse events(Duration of 90-day posaconazole prophylaxis)
Investigators
Erlie Jiang
Director
Institute of Hematology & Blood Diseases Hospital, China