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

NCT ID: NCT04502381

Last Updated: 2023-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2021-12-30

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

Conditions

Pulmonary Mucormycosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention arm

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)

Group Type: EXPERIMENTAL

Inhaled amp B deoxycholate+intravenous liposomal amp B

Intervention Type: DRUG

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

Intervention Type: DRUG

Intravenous liposomal amphotericin B (beginning with 3mg/kg, up to 5 mg/kg), with or without surgery or other antifungals as clinically indicated

Conventional arm

Participants will receive treatment with only intravenous liposomal amphotericin B (3 to 5 mg/kg body weight)

Group Type: ACTIVE_COMPARATOR

Intravenous liposomal amphotericin B alone

Intervention Type: DRUG

Intravenous liposomal amphotericin B (beginning with 3mg/kg, up to 5 mg/kg), with or without surgery or other antifungals as clinically indicated

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 12 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

Principal Investigators

Ratnakara Rao, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

Post graduate Institute medical education and research

Chandigarh, , India

Countries

India

Other Identifiers

NK/6146/DM/452

Identifier Type: -

Identifier Source: org_study_id