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

January 22, 2021 updated by: Erlie Jiang, Institute of Hematology & Blood Diseases Hospital

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

360

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shijia Zhuang, China
        • The Second Hospital of Hebei Medical University
        • Contact:
      • Taiyuan, China
      • Tianjin, China
        • Tianjin Medical University Cancer Institute and Hospital
        • Contact:
      • Tianjin, China
        • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Hematopoietic stem cell transplant patients treated with Posaconazole tablets

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From day 0 to day 22

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The incidence of invasive fungal disease (IFD) and the incidence of Aspergillus infection
Time Frame: 90 days posaconazole prophylaxis and 7 days after prophylaxis ending
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
Plasma concentration of the patients who received different dosages of posaconazole as prophylaxis at different time points
Time Frame: Day 0, 4, 8, 15 and 22
Blood samples were drawn from patients at day 0, 4, 8, 15, and 22 after receiving posaconazole.
Day 0, 4, 8, 15 and 22
The influence of other combined medications for posaconazole plasma concentrations
Time Frame: Duration of 90-day posaconazole prophylaxis
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
Effect of GVHD grading on absorption and utilization of posaconazole tablets (plasma concentration)
Time Frame: Duration of 90-day posaconazole prophylaxis
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
Effect of diarrhea on absorption and utilization of posaconazole tablets (plasma concentration)
Time Frame: Duration of 90-day posaconazole prophylaxis
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
Number/Proportion of patients with immunosuppressive agent application and adjustments
Time Frame: Duration of 90-day posaconazole prophylaxis
Recording of the number/proportion of patients who received immunosuppressive agents or adjustments of agents.
Duration of 90-day posaconazole prophylaxis
Measurement and record of neutrophil counts
Time Frame: Duration of 90-day posaconazole prophylaxis
Measurement of neutrophils in blood samples of patients.
Duration of 90-day posaconazole prophylaxis
Measurement and record of duration of neutropenia
Time Frame: Duration of 90-day posaconazole prophylaxis
Measurement of duration of neutropenia in blood samples of patients.
Duration of 90-day posaconazole prophylaxis
Adverse events
Time Frame: Duration of 90-day posaconazole prophylaxis
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Hematology & Blood Diseases Hospital

Collaborators

The Second Hospital of Hebei Medical University
Tianjin Medical University Cancer Institute and Hospital
Shanxi Bethune Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2021

Primary Completion (Anticipated)

April 1, 2023

Study Completion (Anticipated)

April 1, 2023

Study Registration Dates

First Submitted

January 12, 2021

First Submitted That Met QC Criteria

January 22, 2021

First Posted (Actual)

January 27, 2021

Study Record Updates

Last Update Posted (Actual)

January 27, 2021

Last Update Submitted That Met QC Criteria

January 22, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20200909

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pulmonary Fungal Infection

Clinical Trials on Oral Posaconazole tablets

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United States

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe