Amphotericin Versus Posaconazole for Pulmonary Mucormycosis

NCT ID: NCT05468372

Last Updated: 2024-09-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2025-07-30

Brief Summary

Pulmonary mucormycosis is a serious illness with high morbidity and mortality (approximately 57%). Surgery and antifungal therapy are central in the management of mucormycosis. Unlike rhino-orbital mucormycosis, surgery is not feasible in several patients with pulmonary mucormycosis. Hence, treatment is primarily with antifungal therapy. Amphotericin B is the standard of care in the medical management of mucormycosis. However, amphotericin B is expensive, has significant adverse events, and is available only in parenteral formulation. Posaconazole is effective against Mucorales, and is currently approved for salvage therapy of mucormycosis. Recent evidence suggest that in several patients, posaconazole may be effective as a monotherapy upfront. In the current study posaconazole versus amphotericin B will be evaluated for the management of pulmonary mucormycosis in a randomized clinical trial.

Conditions

Mucormycosis; Pulmonary (Etiology)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Amphotericin B arm (standard of care)

Intravenous liposomal amphotericin B \[5 mg/kg per day\] for at least 4 weeks followed by maintenance therapy. Maintenance therapy (after four weeks of treatment initiation) will be continued for at least 12 weeks or longer as decided by the treating physician. The maintenance therapy will be posaconazole. However, if therapeutic drug monitoring is not possible or the participants opt to use isavuconazole or amphotericin, the same will be permitted and noted

Group Type: ACTIVE_COMPARATOR

Liposomal Amphotericin B

Intervention Type: DRUG

All study subjects will be administered intravenous liposomal amphotericin B [5 mg/kg/day infusion in 5% dextrose solution] over at least 2 hours, as per recommendations. Amphotericin B will be administered for the first seven days in the experimental arm, whereas it will be administered atleast for four weeks in the active comparator arm. Premedication or intravenous hydration will not be routinely administered. For patients experiencing chills, fever, hypotension, nausea, or other non-anaphylactic immediate infusion-related reactions, premedication (acetaminophen, diphenhyramine or hydrocortisone) will be administered 30 to 60 minutes prior to the next dose of amphotericin infusion.

The dose of intravenous amphotericin B will be modified further if required, based on the tolerability, and response to treatment.

Posaconazole arm

Combination of liposomal amphotericin B (5 mg/kg per day) and posaconazole for first 7 days followed by oral posaconazole only (for induction as well as maintenance therapy). The first four weeks of therapy will be called induction therapy

Group Type: EXPERIMENTAL

Posaconazole 600 mg followed by posaconazole 300 mg once daily

Intervention Type: DRUG

Posaconazole will be given as a delayed release tablet, the dose would be 600 mg in two divided doses on day 1, followed by 300 mg once a day from then on. If a subject vomits within 15 minutes of posaconazole tablet administration, the dosing should be repeated as soon as possible, following appropriate antiemetic treatment. The drug will be administered after a meal.

Liposomal Amphotericin B

Intervention Type: DRUG

All study subjects will be administered intravenous liposomal amphotericin B [5 mg/kg/day infusion in 5% dextrose solution] over at least 2 hours, as per recommendations. Amphotericin B will be administered for the first seven days in the experimental arm, whereas it will be administered atleast for four weeks in the active comparator arm. Premedication or intravenous hydration will not be routinely administered. For patients experiencing chills, fever, hypotension, nausea, or other non-anaphylactic immediate infusion-related reactions, premedication (acetaminophen, diphenhyramine or hydrocortisone) will be administered 30 to 60 minutes prior to the next dose of amphotericin infusion.

The dose of intravenous amphotericin B will be modified further if required, based on the tolerability, and response to treatment.

Interventions

Posaconazole 600 mg followed by posaconazole 300 mg once daily

Posaconazole will be given as a delayed release tablet, the dose would be 600 mg in two divided doses on day 1, followed by 300 mg once a day from then on. If a subject vomits within 15 minutes of posaconazole tablet administration, the dosing should be repeated as soon as possible, following appropriate antiemetic treatment. The drug will be administered after a meal.

Intervention Type: DRUG

Liposomal Amphotericin B

All study subjects will be administered intravenous liposomal amphotericin B [5 mg/kg/day infusion in 5% dextrose solution] over at least 2 hours, as per recommendations. Amphotericin B will be administered for the first seven days in the experimental arm, whereas it will be administered atleast for four weeks in the active comparator arm. Premedication or intravenous hydration will not be routinely administered. For patients experiencing chills, fever, hypotension, nausea, or other non-anaphylactic immediate infusion-related reactions, premedication (acetaminophen, diphenhyramine or hydrocortisone) will be administered 30 to 60 minutes prior to the next dose of amphotericin infusion.

The dose of intravenous amphotericin B will be modified further if required, based on the tolerability, and response to treatment.

Intervention Type: DRUG

Other Intervention Names

In the experimental arm, the first seven days of posaconazole will be overlapped with liposomal amphotericin B 5 mg/kg body weight intravenous infusion (similar to the active comparator arm); LAMB

Eligibility Criteria

Inclusion Criteria

Subjects with proven or probable pulmonary mucormycosis. Participants with a suspicion of pulmonary mucormycosis (as defined previously) based on compatible clinical presentation and compatible imaging will be screened for inclusion in the study.

Exclusion Criteria

• Failure to provide informed consent
• Contraindications or hypersensitivity to amphotericin B, posaconazole or their components
• Already received >4 days of antifungals prior to randomization into the study
• Pregnant women
• High chances of mortality within 48 hours of enrolment into the study

Subjects with possible pulmonary mucormycosis will also be excluded, if their diagnosis is not confirmed within four working days of enrollment

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: lead

Responsible Party

Ritesh Agarwal

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Postgraduate Institute of Medical Education and Research

Chandigarh, Chandigarh, India

Site Status: RECRUITING

Countries

India

Central Contacts

Valliappan Muthu

Role: CONTACT

muthu.valliappan@pgimer.edu.in

+917087001389

Facility Contacts

Akshay Raut, MBBS, MD

Role: primary

akshay136913@gmail.com

07087001389

Akshay Raut, MBBS, MD

Role: backup

Valliappan Muthu, MD, DM

Role: backup

Other Identifiers

IEC-INT/2022/DM-262

Identifier Type: -

Identifier Source: org_study_id