Clinical trial

A Randomized Controlled Trial of Amphotericin B Versus Posaconazole for Treating Pulmonary Mucormycosis

Name

IEC-INT/2022/DM-262

Description

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.

Trial arms

Trial start

2022-07-01

Estimated PCD

2023-12-31

Trial end

2024-06-30

Status

Recruiting

Phase

Early phase I

Treatment

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.

Arms:

Posaconazole arm

Other 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)

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.

Arms:

Amphotericin B arm (standard of care), Posaconazole arm

Other names:

LAMB

Size

Primary endpoint

The proportion of participants achieving a successful outcome (complete response or partial response) at the completion of six weeks. The response assessment will be a composite of clinical and radiological as adjudged by a multidisciplinary team

six weeks after randomization

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 30, 'type': 'ESTIMATED'}}

Updated at

2023-11-27

1 organization

2 products

1 indication

Organization

Post Graduate Institute of Medical Education and Research, Chandigarh

Product

Posaconazole

Indication

Mucormycosis

Product

Liposomal Amphotericin B