Posaconazole for Pulmonary Fungal Infection Prophylaxis in Hematopoietic Stem Cell Transplantation Patients

Pulmonary Fungal Infection Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04725942
• Other study ID #: 20200909
• Status: Not yet recruiting
• Start date: January 2021
• Est. completion date: April 2023

Study information

• Verified date: January 2021
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Aiming Pang
• Phone: +86-13820398091
• Email: pangaiming[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 360
• Est. completion date: April 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Lung Diseases, Fungal
• Mycoses
• Pulmonary Fungal Infection

Intervention

Drug:
• Oral Posaconazole tablets
Posaconazole tablets (300 mg Q12h D1) taken orally on the day of transplantation, and followed by 300mg Qd, until 90 days after transplantation.

Locations

Country	Name	City	State
China	The Second Hospital of Hebei Medical University	Shijia Zhuang
China	Shanxi Bethune Hospital	Taiyuan
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin

Sponsors (4)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital	Shanxi Bethune Hospital, The Second Hospital of Hebei Medical University, Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	UGT1A4*3 genotype and plasma concentration of posaconazole	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.	From day 0 to day 22
Secondary	The incidence of invasive fungal disease (IFD) and the incidence of Aspergillus infection	Patients who developed invasive fungal infections, aspergillus infections or death related with IFD infections during posaconazole prophylaxis treatment were recorded in accordance with IFD diagnostic guidelines (Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2020 Sep 12;71(6):1367-1376).	90 days posaconazole prophylaxis and 7 days after prophylaxis ending
Secondary	Plasma concentration of the patients who received different dosages of posaconazole as prophylaxis at different time points	Blood samples were drawn from patients at day 0, 4, 8, 15, and 22 after receiving posaconazole.	Day 0, 4, 8, 15 and 22
Secondary	The influence of other combined medications for posaconazole plasma concentrations	Blood samples were drawn at day 0, 4, 8, 15 and 22 after receiving posaconazole, while all combined medications during posaconazole prophylaxis were recorded and IFD cases were monitored during the study period.	Duration of 90-day posaconazole prophylaxis
Secondary	Effect of GVHD grading on absorption and utilization of posaconazole tablets (plasma concentration)	Gastrointestinal GVHD grades (I-IV) were recorded according to patient symptoms and posaconazole plasma concentrations were measured using blood samples of each patient after receiving posaconazole tablets at day 0, 4, 8, 15 and 22.	Duration of 90-day posaconazole prophylaxis
Secondary	Effect of diarrhea on absorption and utilization of posaconazole tablets (plasma concentration)	Diarrhea (acute watery diarrhea, acute hemorrhagic diarrhea, persistent diarrhea, and diarrhea with severe malnutrition) was recorded according to patient symptoms, and posaconazole plasma concentrations were measured using blood samples of each patient after receiving posaconazole tablets at day 0, 4, 8, 15 and 22.	Duration of 90-day posaconazole prophylaxis
Secondary	Number/Proportion of patients with immunosuppressive agent application and adjustments	Recording of the number/proportion of patients who received immunosuppressive agents or adjustments of agents.	Duration of 90-day posaconazole prophylaxis
Secondary	Measurement and record of neutrophil counts	Measurement of neutrophils in blood samples of patients.	Duration of 90-day posaconazole prophylaxis
Secondary	Measurement and record of duration of neutropenia	Measurement of duration of neutropenia in blood samples of patients.	Duration of 90-day posaconazole prophylaxis
Secondary	Adverse events	Record of the number, incidence and frequency of adverse events (AE) during the study period and judge whether the AE is drug related, serious, or special interest AE. AE severity is determined according to MedDRA v23.1.	Duration of 90-day posaconazole prophylaxis