Combined Inhalational With Intravenous Amphotericin B Versus Intravenous Amphotericin B Alone for Pulmonary Mucormycosis

Pulmonary Mucormycosis Clinical Trial

Official title:

A Randomized Controlled Trial of Combined Inhalational With Intravenous Amphotericin B in Comparison With Intravenous Amphotericin B Alone for Treatment of Pulmonary Mucormycosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04502381
• Other study ID #: NK/6146/DM/452
• Status: Completed
• Phase: Phase 2
• Start date: July 1, 2020
• Est. completion date: December 30, 2021

Study information

• Verified date: November 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 30, 2021
• Est. primary completion date: October 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Mucormycosis
• Pulmonary Mucormycosis
• Zygomycosis

Intervention

Drug:
• Inhaled amp B deoxycholate+intravenous liposomal amp B
Intravenous liposomal amphotericin B (beginning with 3mg/kg) along with inhaled amphotericin as below: Amp-B deoxycholate 50 mg (Amphotret™ Bharat serums and vaccines limited), will be dissolved in 10 mL distilled water. 2 mL of the reconstituted amphotericin B solution will be transferred into the drug chamber of a breath actuated nebulizer (Lupineb Ultra kit breath actuated nebulize which contains aeroclipse XL Reusable Breath Actuated Nebulizer and DeVilbiss 3655 compressor). 3 mL of distilled water is added to 2 mL of the reconstituted amphotericin B. The nebulization is continued till the chamber is emptied of the drug or the patient does not tolerate the therapy. The first three doses of amphotericin B nebulization will be under the direct supervision of a physician. If tolerated, nebulization will be continued twice a day till tolerated or till response.The patient will complete a VAS score for cough after nebulization.
• Intravenous liposomal amphotericin B alone
Intravenous liposomal amphotericin B (beginning with 3mg/kg, up to 5 mg/kg), with or without surgery or other antifungals as clinically indicated

Locations

Country	Name	City	State
India	Post graduate Institute medical education and research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response (clinical and radiological improvement) at the end of six weeks of 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"	6 weeks after the start of therapy
Primary	Adverse events related to therapy	Adverse events related to therapy (especially, incidence of bronchospasm and acute kidney injury)	till 6 weeks from randomization (start of therapy)
Secondary	In-hospital mortality	Death due to any cause in-hospital	During hospital stay, approximately till 6 weeks from randomization (start of therapy)
Secondary	90 day mortality	Death due to any cause till 90 days of randomization	90 days from the date of randomization
Secondary	Proportion of subjects requiring discontinuation or modification of therapy due to adverse events	Number of participants withdrawing therapy in each arm, divided by the total number of patients in the same arm	till 6 weeks from randomization (start of therapy)