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

NCT04502381 | Completed Phase 2

• 1 other identifier: NK/6146/DM/452
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Mucormycosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• In-hospital mortality

  During hospital stay, approximately till 6 weeks from randomization (start of therapy)

• 90 day mortality

  90 days from the date of randomization

• Proportion of subjects requiring discontinuation or modification of therapy due to adverse events

  till 6 weeks from randomization (start of therapy)

Study Arms (2)

Intervention arm

EXPERIMENTAL

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)

Drug: Inhaled amp B deoxycholate+intravenous liposomal amp B; Drug: Intravenous liposomal amphotericin B alone

Conventional arm

ACTIVE COMPARATOR

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

Drug: Intravenous liposomal amphotericin B alone

Interventions

Inhaled amp B deoxycholate+intravenous liposomal amp B 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.

Intervention arm

Intravenous liposomal amphotericin B alone 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; Intervention arm

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Post graduate Institute medical education and research

Chandigarh, 160012, India

Location

Study Officials

• Ratnakara Rao, MBBS, MD

  Post Graduate Institute of Medical Education and Research, Chandigarh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 1, 2020
• First Posted: August 6, 2020
• Study Start: July 1, 2020
• Primary Completion: October 30, 2021
• Study Completion: December 30, 2021
• Last Updated: November 27, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)