Clinical trial NCT04725942: Posaconazole for Pulmonary Fungal Infection Prophylaxis in Hematopoietic Stem Cell Transplantation Patients
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pulmonary Fungal Infection
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Shanxi Bethune Hospital
name: The Second Hospital of Hebei Medical University
name: Tianjin Medical University Cancer Institute and Hospital
First posted: 2021-01-27
Enrollment: 360
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hematopoietic stem cell transplant patients treated with Posaconazole tablets

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.

Eligibility criteria: 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

Primary outcomes:
measure: UGT1A4*3 genotype and plasma concentration of posaconazole
timeFrame: From day 0 to day 22
Secondary outcomes:
measure: The incidence of invasive fungal disease (IFD) and the incidence of Aspergillus infection
timeFrame: 90 days posaconazole prophylaxis and 7 days after prophylaxis ending
measure: Plasma concentration of the patients who received different dosages of posaconazole as prophylaxis at different time points
timeFrame: Day 0, 4, 8, 15 and 22
measure: The influence of other combined medications for posaconazole plasma concentrations
timeFrame: Duration of 90-day posaconazole prophylaxis
measure: Effect of GVHD grading on absorption and utilization of posaconazole tablets (plasma concentration)
timeFrame: Duration of 90-day posaconazole prophylaxis
measure: Effect of diarrhea on absorption and utilization of posaconazole tablets (plasma concentration)
timeFrame: Duration of 90-day posaconazole prophylaxis
measure: Number/Proportion of patients with immunosuppressive agent application and adjustments
timeFrame: Duration of 90-day posaconazole prophylaxis
measure: Measurement and record of neutrophil counts
timeFrame: Duration of 90-day posaconazole prophylaxis
measure: Measurement and record of duration of neutropenia
timeFrame: Duration of 90-day posaconazole prophylaxis
measure: Adverse events
timeFrame: Duration of 90-day posaconazole prophylaxis
Other outcomes:
Locations:
city: Shijia Zhuang
country: China
facility: The Second Hospital of Hebei Medical University
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
Study officials:
References: