Comparative Evaluation of Effectiveness of Standard of Care Alone and in Combination With Homoeopathic Treatment in COVID-19-Related Rhino-Orbito-Cerebral Mucormycosis (ROCM): Protocol for a Single Blind, Randomized Controlled Trial

Abstract

Background: Rhino-orbital-cerebral mucormycosis (ROCM) is the most common (45%-74%) mucormycosis in India. With contemporary medical care, ROCM has a mortality rate of 40%-50% and 70% of survivors are left with residual defects. Recently, several cases of mucormycosis in people with COVID-19 have been increasingly reported worldwide, from India, due to immune dysregulation caused by SARS-CoV-2. To reduce the high mortality rate and residual defect in most survivors under the guidelines of the Ministry of AYUSH, the Government of India recommended homoeopathy as an add-on therapy to maximize the effectiveness of standard treatment in conventional therapy.

Objective: This study aimed to evaluate the role of existing homoeopathic treatment as an adjuvant therapy in patients with COVID-19-related ROCM and enhancing the survival of the patients hospitalized due to COVID-19 infection and to access the initial treatment response and duration required for significant or complete recovery in patients receiving adjuvant treatment.

Methods: This superiority, randomized controlled clinical trial would include two parallel comparator groups A and B. Group A would be the experimental group and would receive homoeopathic treatment along with the standard line of treatment as per investigational medicinal product (IMP) and group B would be the control arm and would receive standard line of treatment as per IMP along with identical placebo. Allocation would be 1:1 through randomization. Based on the inclusion and exclusion criteria, 36 participants per arm would be screened. Participants would be assessed clinically twice a day and magnetic resonance imagery or endoscopy cum-biopsy would be assessed on days 1, 14, and 28. Laboratory investigations may vary as per demand of disease conditions.

Results: In India, the COVID-19 pandemic, particularly during the second wave, resulted in a surge of mucormycosis cases among patients with COVID-19. At the time this protocol was being developed, there was a significant spike in mucormycosis cases in India, particularly in Mumbai (June 2021). However, by the time the Central Council for Research in Homoeopathy obtained the necessary approvals and ethical clearance for the study, the incidence of mucormycosis had drastically declined (September 2021). As a result, the study was not initiated and registered. The authors feel it is their ethical responsibility to share the reviewed protocol with the medical community as a reference for future work.

Conclusions: This study aims to evaluate the role of existing homoeopathic medicines as an adjuvant therapy in managing COVID-19-related ROCM, potentially contributing to the use of homoeopathy as an evidence-based medical approach. The protocol can also serve as a valuable resource for clinicians and researchers addressing mucormycosis cases unrelated to COVID-19, particularly in immunocompromised patients. It would help ensure preparedness, whether or not sufficient evidence is available, in the event of a future health emergency.

International registered report identifier (irrid): PRR1-10.2196/57905.

Keywords: India; Rhino-orbital-cerebral mucormycosis, randomized controlled trial, homoeopathy, fungus, CE-MRI PNS mucormycosis; conventional therapy; ethical; homoeopathic medicines; management; medical care; mortality; mortality rate; recovery; survival.

Figure 1

Flow diagram of study design. CEMRI PNS: Contrast-Enhanced Magnetic Resonance Imaging of Para Nasal sinus; CBC: complete blood count; CT: computed tomography; ESR: erythrocyte sedimentation rate; HbA1c: hemoglobin A1c; IMP: investigational medicinal product; KFT: kidney function test; KOH: potassium hydroxide; LFT: liver function test; PPBS: postprandial blood sugar; ROCM: rhino-orbital-cerebral mucormycosis.