Efficacy and Safety of Systematic Therapy and Bronchoscopic Interventional Treatment for Pulmonary Mucormycosis

Evaluation of the Effectiveness and Safety of Transbronchoscopic Infusion of Amphotericin B + Inhalation of Amphotericin B + Transbronchoscopic Debridement + Systematic Antifungal Multimodal Treatment of Pulmonary Mucormycosis

Evaluation of the effectiveness and safety of transbronchoscopic local precision infusion of amphotericin B + transoral nebulized inhalation of amphotericin B + transbronchoscopic interventional debridement + liposomal amphotericin B + posaconazole or Isavuconazole multimodal treatment of pulmonary mucormycosis

Study Overview

• Status: Enrolling by invitation
• Conditions: Pulmonary Mucormycosis
• Intervention / Treatment: Procedure: transbronchoscopic interventional debridement

Detailed Description

Key rationale for the treatment of mucormycosis is early surgical intervention, including local debridement and removal of infected tissues or organs if possible. Systemic antifungal therapy is also necessary for mucormycosis, including amphotericin B liposomes and deoxycholates, Isavuconazole, posaconazole, and so on. Antifungal drug therapy has a mortality rate of up to 40%, which can be reduced to 23% when combined with surgical treatment. However, some patients who are unable to tolerate surgical procedures on the chest when in bad condition, especially patients with hematological malignancies undergoing hematopoietic stem cell transplantation, are susceptible to multiple mucormycosis of the lungs, and the mortality rate of untreated systemically disseminated mucormycosis infections is high at 80%. Isavuconazole, so we aim to explore the multimodal treatment of liposomal amphotericin B + posaconazole or esaconazole + transbronchoscopic localized precise instillation of amphotericin B + oral nebulized inhalation of amphotericin B + transbronchoscopic interventional debridement to alleviate the pulmonary mucormycosis in chest imaging and reduce the mortality rate of patients with mucormycosis infection.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Tsinghua Changgung Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects suspected of pulmonary mucormycosis by clinical radiology will be enrolled in the study if the pathologic or microbiological diagnosis of mucormycosis (smear showing sterile mycelium, culture or molecular evidence of mucormycosis) is confirmed.
• Cases of diffuse mucormycosis will only be included if lung infection is confirmed pathologically or microbiologically by respiratory secretions or biopsy samples.
• Ability to tolerate bronchoscopy.

Exclusion Criteria:

• Pregnant and breastfeeding female patients
• Age <18 years
• Patients with HIV infection
• Contraindications to bronchoscopy (including platelet count < 100 x 109/L, active hemoptysis, severe respiratory or heart failure, severe arrhythmia, unstable angina or hypertension, severe pneumothorax or mediastinal emphysema, patients with acute myocardial infarction, cerebral infarction, and cerebral hemorrhage within 3 months
• Patients unable to tolerate bronchoscopy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Multimodal Treatment; combination drug therapy：liposomal amphotericin B + posaconazole or Isavuconazole：3-5mg/kg/day+ Posaconazole 300 mg once daily; target blood trough concentration is >1ug/mL; if posaconazole is unavailable, Isavuconazole 200 mg once daily may be an alternative.; transbronchoscopic local precision infusion of amphotericin B: Maximum dose not more than 30mg per session; transoral nebulized inhalation of amphotericin B：amphotericin B 10mg + 5ml of sterilized water for injection, inhalation 2/day. 4)transbronchoscopic interventional debridement

Procedure: transbronchoscopic interventional debridement; combination drug therapy：liposomal amphotericin B + posaconazole or Isavuconazole：3-5mg/kg/day+ Posaconazole 300 mg once daily; target blood trough concentration is >1ug/mL; if posaconazole is unavailable, Isavuconazole 200 mg once daily may be an alternative.; transbronchoscopic local precision infusion of amphotericin B: Maximum dose not more than 30mg per session; transoral nebulized inhalation of amphotericin B：amphotericin B 10mg + 5ml of sterilized water for injection, inhalation 2/day. 4)transbronchoscopic interventional debridement; Other Names: transbronchoscopic local precision infusion of amphotericin B; transoral nebulized inhalation of amphotericin B; liposomal amphotericin B + posaconazole or Isavuconazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of complete or partial response at 4 weeks	Complete response: Resolution of all clinical signs and symptoms and more than 90% of lesions visible on radiology; Partial response: Clinical improvement and >50% improvement in findings on radiology	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of complete or partial response at 12 weeks	Complete response: Resolution of all clinical signs and symptoms and more than 90% of lesions visible on radiology; Partial response: Clinical improvement and >50% improvement in findings on radiology	12 weeks
Survival rate at 6 months	estimates using all-cause mortality at 12 months	6 months
the incidence of adverse reactions related to this comprehensive treatment at 4 weeks	The adverse reactions were assessed based on the Common Terminology Criteria for Adverse Events 5.0(CTCAE5.0)	4 weeks

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Investigators: Principal Investigator: Manting Liu, MD, Tsinghua University

Study record dates

Study Major Dates

• Study Start (Estimated): July 30, 2024
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 24, 2024
• First Submitted That Met QC Criteria: July 3, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: treatment; bronchoscopy; pulmonary mucormycosis
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Mucormycosis; Zygomycosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole; Isavuconazole; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: ST&BITPM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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