Early treatment with the FDA-approved antiparasitic drug nitazoxanide prevents mild or moderate COVID-19 symptoms from progressing to severe illness and hospitalization, a clinical study co-led by USF Health’s Christian Bréchot, MD, PhD, indicates.

The Phase 3 randomized, double-blind, controlled clinical trial, conducted at 36 centers in the U.S. and Puerto Rico, was led by Jean-Francois Rossignol, MD, PhD, executive chairman of Tampa-based Romark LLC, and Christian Brechot, MD, PhD, president of the Global Virus Network; associate vice president for International Partnerships and Innovation at USF; and professor, Division of Infectious Disease, Department of Internal Medicine at the USF Health Morsani College of Medicine.

The findings posted April 20 to medRxiv, a preprint server for health sciences.

USF Health’s Christian Brechot, MD, PhD, co-led the multicenter clinical study.

“Combining safe, potent therapies with vaccination programs will be critical to controlling this pandemic,” study principal investigator Dr. Brechot said. “Despite the remarkable advances in developing effective COVID-19 vaccines, we still urgently need new treatments to help prevent severe disease and hospitalizations.”

This is particularly the case earlier in the disease – before the COVID-19 virus replicates extensively and infection spreads from the lungs, potentially triggering an immune system-induced “cytokine storm” that damages other organs. Monoclonal antibodies, while achieving promising results when infused early enough, are costly, prone to resistance by viral mutations, and must be administered in a hospital or clinic, Dr. Brechot added.

Nitazoxanide, an existing drug widely prescribed to treat intestinal parasites, has a proven safety record in children and adults. In cell culture studies, it has been shown to inhibit replication of several different respiratory viruses, including the human coronavirus MERS, influenza viruses, and rhinoviruses. Researchers attribute the drug’s broad-spectrum antiviral activity to its interference with cell pathways that the virus exploits to multiply. Recently, nitazoxanide was identified as a promising candidate for early treatment of SARS-CoV-2.

With this in mind, the team led by Dr. Rossignol and Dr Brechot investigated whether nitazoxanide, could be repurposed to stop mild or moderate COVID-19 from worsening.

In the latest clinical trial, the researchers tested the effectiveness of nitazoxanide in 379 outpatients, ages 12 to 83, with laboratory-confirmed mild or moderate COVID-19. Study participants (whose COVID respiratory symptoms began no more than 72 hours before entering the trial) were randomized into one of two groups, both treated for five days. One group received 300 mg. extended release nitazoxanide tablets twice daily (a 600 mg dose); the second group received placebo tablets matching the real drug’s appearance twice daily.

Monoclonal antibodies, which have shown promise for early COVID-19 treatment, are costly, administered at a hospital or clinic, and prone to resistance by viral mutations.

Among the findings of the efficacy analysis:

• Time to sustained response (a measure of how long COVID mild or moderate symptoms lasted) was not reduced by nitazoxanide.

• Nitazoxanide treatment was associated with an 85% decrease in progression to severe illness, compared to placebo. Only one of all 184 outpatients in the nitazoxanide group progressed to severe disease (a rate of 0.5%), while seven out of 195 (3.6%) in the placebo group did.

• A subgroup of 238 study participants (63% of the total 379) were at high risk of developing severe COVID illness based on Centers for Disease Control and Prevention (CDC) criteria (age, underlying medical conditions, etc.). Of these higher-risk individuals the rate of progression to severe disease was significantly lower for the nitazoxanide-treated group (0.9%), than for the placebo group (5.6%).

• Treatment reduced the rate of hospitalization by 79% in the nitazoxanide group (0.5%), compared to the placebo group (2.6%).

The researchers emphasize that larger studies are needed to confirm their results.

New, easily accessible antiviral treatments are still urgently needed to prevent the progression of mild or moderate COVID-19 to severe illness and hospitalizations.

“The availability of a safe, oral, scalable, host-directed antiviral for the early treatment of COVID-19 in persons at high risk of severe illness could play an important role in reducing the number of severe illnesses and hospitalizations during this ongoing major public health crisis,” they concluded.

The study was funded by the Romark Institute for Medical Research.