Combined Inhalational With Intravenous Amphotericin B Versus Intravenous Amphotericin B Alone for Pulmonary Mucormycosis
- Conditions
- Pulmonary Mucormycosis
- Interventions
- Drug: Intravenous liposomal amphotericin B aloneDrug: Inhaled amp B deoxycholate+intravenous liposomal amp B
- Registration Number
- NCT04502381
- Lead Sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Brief Summary
To assess the safety and feasibility of combined inhalational and intravenous amphotericin B therapy for the treatment of pulmonary mucormycosis. And compare the efficacy of combined therapy with that of intravenous amphotericin B alone.
- Detailed Description
Pulmonary mucormycosis is a relatively a rare disease with a high mortality. The angioinvasion associated with mucormycosis prevents efficient drug delivery at the diseased site. Inhaled amphotericin B achieves drug levels in lung tissue and has been shown to be useful in several diseases including chronic pulmonary and allergic bronchopulmonary aspergillosis. Further inhaled forms of amphotericin B are associated with less nephrotoxicity and other systemic adverse effects. The role of inhaled amphotericin B in pulmonary mucormycosis has been previously demonstrated in murine models and anecdotal reports. The study hypothesis is that combined therapy with inhalational and intravenous amphotericin B is likely to result in better outcomes as compared with intravenous amphotericin B alone for treatment of pulmonary mucormycosis
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Subjects with a clinicoradiologic suspicion of pulmonary mucormycosis will be enrolled if the diagnosis of mucormycosis is pathologically or microbiologically (smear showing aseptate hyphae, culture or molecular evidence showing Mucorales) confirmed. Cases of disseminated mucormycosis will be included, only if the pulmonary infection is confirmed pathologically or microbiologically from respiratory secretions or biopsy samples
- Lack of informed consent
- Hypersensitivity to amphotericin B or any component of the formulation
- Pregnancy
- High likelihood of death within 48 h of enrolment
- Suspected pulmonary mucormycosis without histological or microbiologic proof
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Conventional arm Intravenous liposomal amphotericin B alone Participants will receive treatment with only intravenous liposomal amphotericin B (3 to 5 mg/kg body weight) Intervention arm Inhaled amp B deoxycholate+intravenous liposomal amp B The study participants in the intervention arm will receive nebulization with amphotericin B deoxycholate (10 mg twice a day every alternate day, as described below) along with intravenous liposomal amphotericin B (3 to 5 mg/kg body weight) Intervention arm Intravenous liposomal amphotericin B alone The study participants in the intervention arm will receive nebulization with amphotericin B deoxycholate (10 mg twice a day every alternate day, as described below) along with intravenous liposomal amphotericin B (3 to 5 mg/kg body weight)
- Primary Outcome Measures
Name Time Method Overall response (clinical and radiological improvement) at the end of six weeks of start of therapy 6 weeks after the start of therapy Complete response: Survival and resolution of all attributable symptoms and signs of disease plus Resolution of radiological lesion(s); persistence of only a scar or postoperative changes can be equated with complete radiological response Partial response: Survival and improvement of attributable symptoms and signs of disease plus At least 25% reduction in diameter of radiological lesion OR In cases of radiological stabilization (defined as 0%-25% reduction in the diameter), resolution of all attributable symptoms and signs of fungal disease can be equated with a partial response Stable response: Survival and minor or no improvement in attributable symptoms and signs; plus Radiological stabilization (defined as 0%-25% reduction in diameter) Progression: Worsening clinical symptoms or signs plus New sites of disease or radiological worsening Death Complete and partial response will be called "success"
Adverse events related to therapy till 6 weeks from randomization (start of therapy) Adverse events related to therapy (especially, incidence of bronchospasm and acute kidney injury)
- Secondary Outcome Measures
Name Time Method 90 day mortality 90 days from the date of randomization Death due to any cause till 90 days of randomization
Proportion of subjects requiring discontinuation or modification of therapy due to adverse events till 6 weeks from randomization (start of therapy) Number of participants withdrawing therapy in each arm, divided by the total number of patients in the same arm
In-hospital mortality During hospital stay, approximately till 6 weeks from randomization (start of therapy) Death due to any cause in-hospital
Trial Locations
- Locations (1)
Post graduate Institute medical education and research
🇮🇳Chandigarh, India