Posaconazole Tablet As Primary Prophylaxis of HSCT Patients with Gastrointestinal GVHD

Evaluation of Posaconazole Tablet As Primary Prophylaxis of Hematopoietic Stem Cell Transplant Patients with Gastrointestinal GVHD

This is a prospective investigation using a nonrandomized, single-arm design. Posaconazole tablet will be given at a dose of 300mg q12h on day 1 and 300mg qd from day 2 for patients who receive HSCT as the primary prophylaxis of IFD, after which the Posaconazole plasma concentration on day 5 will be examined.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hematopoietic Stem Cell Transplantation; Graft Versus Host Disease; Invasive Fungal Disease
• Intervention / Treatment: Drug: Posaconazole tablet

Detailed Description

This is a prospective investigation using a nonrandomized, single-arm design. Posaconazole tablet will be given at a dose of 300mg q12h on day 1 and 300mg qd from day 2 for patients who receive HSCT as the primary prophylaxis of IFD, after which the Posaconazole plasma concentration on day 5 will be examined. Once patients developed GI GVHD, first line therapy and second line treatment will be reviewed according to the condition, besides which the Posaconazole plasma concentration would be detected again on the first, third and fifth day after onset of GI GVHD symptoms to monitor the impact of GI GVHD on the Posaconazole plasma concentration. The primary endpoint was the incidence of breakthrough fungal infection (BFI) including proven, probable and possible fungal infection

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

Study Locations

• China
  • Tianjin, China, 300020
    • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

1. Patient undergoing Hematopoietic stem cell transplantation who meet the inclusion criteria and do not meet the exclusion criteria can enroll in this study.
2. Ages eligible for study: 18-75
3. Sexes eligible for study: All
4. Race: Chinese
5. Ethnicity: All

Description

Inclusion Criteria:

1. Patients with hematologic diseases who undergoes hematopoietic stem cell transplantation.
2. Patients who receive Posaconazole tablet as primary prophylaxis of invasive fungal disease.

3. Patients developing or developed acute gastrointestinal GVHD which require systemic immunosuppressive therapy of corticosteroids with- or-without other immunosuppressive agents including calcineurin inhibitors.

   Gastrointestinal GVHD grades (I-IV) were recorded according to the Glucksberg criteria.

4. Patients themselves or their authorized clients agree to participate in the clinical study and sign the informed consent

Exclusion Criteria:

1. refuse to enroll
2. patients have known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study medication used.
3. pregnant or lactating females
4. take drugs known to interfere with azole antifungal agents, including terfenadine, cisapride and ebastine, within 24h before Posaconazole application; astemizole at enrollment or within 10 days before Posaconazole application; or cimetidine, rifampin, carbamazepine, phenytoin, rifamycin, barbiturates, isoniazid, catharanthine and anthracyclines within 24 h before Posaconazole application
5. have an ECG with a prolonged QTc interval (QTc greater than 500 ms);
6. have severe renal insufficiency, alanine transaminase, aspartate transaminase, alkaline phosphatase or total bilirubin levels more than two-times the upper limit of normal;
7. patients are expected to survive no more than 72 h;
8. Those with evidence of active fungal infection within 3 weeks prior to enrollment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Posaconazole tablet; Posaconazole tablet will be given at a dose of 300mg q12h on day 1 and 300mg qd from day 2 for patients who receive HSCT as the primary prophylaxis of IFD, after which the Posaconazole plasma concentration on day 5 will be examined.

Drug: Posaconazole tablet; Posaconazole tablet will be given at a dose of 300mg q12h on day 1 and 300mg qd from day 2 for patients who receive HSCT as the primary prophylaxis of IFD, after which the Posaconazole plasma concentration on day 5 will be examined. Once patients developed GI GVHD, first line therapy and second line treatment will be reviewed according to the condition, besides which the Posaconazole plasma concentration would be detected again on the first, third and fifth day after onset of GI GVHD symptoms to monitor the impact of GI GVHD on the Posaconazole plasma concentration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
primary endpoint	1. The incidence of breakthrough fungal infection (BFI) including proven, probable and possible fungal infection	From 7 days after starting posaconazole prophylaxis post-transplant to 7 days after the end of prophylaxis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2	Posaconazole plasma concentration	Day 5 after posaconazole administration, and Days 1, 3, and 7 after the onset of gastrointestinal GVHD
3	Gastrointestinal GVHD grade, diarrhea status (frequency, volume), use and adjustment of immunosuppressants, neutrophil count	From the first day of posaconazole prophylaxis for IFD post-transplant to the end of prophylaxis.
4	Adverse events	From the first day of posaconazole prophylaxis for IFD post-transplant to the end of prophylaxis.

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Aiming Pang, doctor, Hematopoietic stem cell transplantation Center

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Estimated): November 20, 2024

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; graft versus host disease; primary prophylaxis; invasive fungal disease
• Additional Relevant MeSH Terms: Immune System Diseases; Infections; Bacterial Infections and Mycoses; Invasive Fungal Infections; Mycoses; Graft vs Host Disease; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: QTJC2024039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing is not considered for the time being due to patient privacy concerns.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes