INTRODUCTION
Over the five decades, Amphotericin B has been a cornerstone in treating invasive fungal infections and visceral leishmaniasis in India.[1] The traditional formulations were associated with nephrotoxicity and infusion-related side effects. The discovery of Liposomal Amphotericin B overcame this issue. In the aftermath of COVID-19, various formulations of Amphotericin B have been explored. This study aims to analyze amphotericin clinical trials registered in the Clinical Trial Registry of India (CTRI) over the past 17 years.
MATERIALS AND METHODS
A systematic search of the CTRI from July 2007 to December 2025 identified 60 amphotericin trials utilizing the keywords “Amphotericin B,” “Antifungal,” and “Amphotericin.” After excluding 11 irrelevant studies, 49 trials were analyzed for study design, formulation, therapeutic area, and funding source. Data were analyzed using the SPSS Version 25 (IBM Corporation, Armonk, New York, USA).
RESULTS
From July 2007 to December 2024, 80,912 studies were registered in the CTRI. Of these, only 49 studies (0.06%) focused on Amphotericin clinical trials. A marked surge in amphotericin trials was observed from 2020 to 2024 following COVID-19. Among the 49 studies, 34 (69.38%) were interventional, 4 (8.16%) were observational studies, 4 (8.16%) were BA/BE, and 7 were Postmarketing Surveillance (14.28%). Most Amphotericin trials registered on CTRI targeted visceral leishmaniasis (28.57%), followed by candidiasis (16.32%), COVID-19 (14.28%), invasive fungal therapy (12.24%), and chronic lower respiratory infection (10.20%), immunocompromised, eye disorders (8.16%), and stress incontinence (2.04%). Among the various formulations, intravenous (IV) administration remains the most widely studied, with Liposomal Amphotericin B accounting for 34 trials, primarily targeting visceral leishmaniasis and postkala-azar dermal leishmaniasis.
Among 34, a single trial compared the sonicated gel and unsonicated drop formulations of Liposomal Amphotericin B. Two trials investigated the use of conventional amphotericin for candidiasis and invasive fungal infections in the intensive care unit patients. Trials were also done in topical and localized drug delivery methods of Amphotericin. Lipid-based Amphotericin gel had been explored for mucocutaneous and cutaneous fungal infections, vulvovaginal candidiasis, and mucormycosis in four trials. In addition, intrastromal injection was evaluated for keratitis in two trials, while intravitreal injection was investigated for endophthalmitis in two trials. Other novel administration routes include nebulized amphotericin (1 trial) for aspergilloma, intranasal (1 trial), peribulbar (1 trial), intracameral (1 trial), and Amphotericin B lipid emulsion (1 trial), signifying a shift toward localized and less invasive treatment approaches. In terms of funding, the pharmaceutical companies sponsored 20 trials (40.81%), followed by 13 academic trials (26.53%), 8 by non-government organizations, and 8 by government-funded trials (16.32%).
DISCUSSION
Fungal infection is often underappreciated in clinical practice, with a prevalence ten times higher than tuberculosis, affecting approximately 4.1% of the population in India.[1] In 2020, India contributed 18% of the global kala-azar burden, this had been decreased with antifungal treatment.[2] Amphotericin has been the gold standard for fungal infections, with newer formulations and different routes of administration reducing systemic toxicity and improving efficacy.[3] Nanotechnology advancements have enabled targeted drug delivery, and several oral Amphotericin formulations at different stages of preclinical development are in the pipeline.[4,5]
The present study analyzed amphotericin trials registered in CTRI over 17 years. Only 0.06% of the trials were registered in CTRI. A surge in trials post-COVID-19 underscores its importance. Liposomal Amphotericin B dominated due to its efficacy and safety. Most trials were interventional, while some explored comparative drug delivery approaches. A notable trend is the shift toward localized delivery methods to enhance efficacy and minimize systemic toxicity. While IV formulations remain dominant, emerging strategies such as tracheoscopic instillation and intrapleural irrigation could revolutionize treatment.[6] These findings underscore the need for ongoing research to optimize Amphotericin formulations and improve the patient outcomes.
CONCLUSION
The present study highlights amphotericin trials in India. Post-COVID-19, trials increased, emphasizing its vital role. Liposomal Amphotericin B remains favored for safety, while amphotericin deoxycholate persists in the resource-limited settings. The shift toward localized delivery methods aims to enhance efficacy. Future research should explore comparative effectiveness, pharmacokinetics, cost-efficacy, and long-term safety to refine treatment approaches.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
I would like to thank my entire faculty, Department of Pharmacology, SRM Medical College for their unwavering support.
Funding Statement
Nil.
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