Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19

Abstract

Background Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro . Objective We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. Methods This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. Results Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). Conclusion Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. Clinicaltrials.gov Identifier NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569 .

Treatments for COVID-19: Lessons from 2020 and new therapeutic options

“… Low (small sample size) In all the study population, the incidence of clinical deterioration was below 3%. NCT04716569 [ 50 ] Mild Egypt 57 IVR significantly reduced durations of fever, cough, dyspnea, and anosmia, as well as the duration of detectable virus in the upper respiratory tract. Low (small sample size) Larger studies in patients with COVID-19 are needed to further investigate the therapeutic potential of IVR (eg, NCT04529525).…”

“…Other repurposed drugs potentially targeting multiple steps of the SARS-CoV-2 life cycle are currently being tested, such as ivermectin (IVM), a broad-spectrum antiparasitic agent with previously reported antiviral activity in vitro [ 47 , 48 , 49 ]. Although a small study on 57 patients with mild COVID-19 showed a reduction in symptom duration and viral detection in the URT of treated patients [ 50 ], no robust evidence to support its clinical use was provided by other studies [ 51 , 52 ] or by a recent Cochrane meta-analysis [ 53 ].…”

Can the Nasal Cavity Help Tackle COVID-19?

“…In a paper published by Aref et al [129] the nasal delivery of Ivermectin was discussed. Mucoadhesive nanosuspension was developed as a drug delivery platform to investigate possible effects in mild COVID-19 patients.…”

Characteristics of published/registered clinical trials on COVID-19 treatment: A systematic review

“…Multiple RCTs have studied ivermectin use in COVID-19 patients. Some RCTs could not found any clinical efficacy of ivermectin [63][64][65], while others have reported faster time to recovery of COVID-19 disease [66][67][68][69][70], a remarkable decrease of cytokines and inflammatory markers [67,68], faster viral clearance [71], or decrease in mortality rate [67,68] in participants who received ivermectin in comparison with the standard treatment protocol. Nevertheless, the majority of these RCTs had methodological issues like small sample sizes, various ivermectin dosages, and different concomitant drugs given to the patients.…”