An early clinical trial of a drug commonly used to treat parasitic infections cut the length of flu symptoms by about a day in patients who didn't have severe disease, a result that appears to be on par with neuraminidase inhibitors, the gold standard for treatment.
The drug studied—nitazoxanide—has a different mechanism of action than neuraminidase inhibitors and could be useful alone or in combination with other drugs as an option for treating antiviral-resistant flu strains, according to the research team, who reported their findings today in an early online edition of Lancet Infectious Diseases.
Currently, the drug is licensed in the United States to treat Cryptosporidium and Giardia infections, and it is widely used in Latin America for treating intestinal parasitic illnesses. It can inhibit flu virus replication by blocking the maturation of viral hemagglutinin and has also been shown in cell culture studies to inhibit other respiratory viruses, including parainfluenza virus, coronaviruses, and respiratory syncytial virus.
The goal of the study was to explore the safety and efficacy of a 300-mg controlled-release tablet designed to deliver blood concentrations needed for treating viral respiratory illnesses. The study was sponsored by Romark Laboratories, the maker of the drug.
The study group included 624 patients aged 12 to 65 years who were treated at 74 primary care clinics between Dec 27, 2010, and Apr 30, 2011. Researchers recruited those who had fever, at least one respiratory symptom, and at least one other symptom of flu, such as muscle aches or chills within 48 hours of symptom onset.
The randomized trial compared the time from initiation of treatment to alleviation of symptoms for two different dosages of nitazoxanide, 300 mg or 600 mg, or placebo, all taken twice a day for 5 days. Patients were asked to record their symptoms along with any adverse events twice a day in a diary. A nurse checked in with patients on study days 2 through 5 to ask about symptoms and any complications. Patients were asked not to take antiviral drugs, but they were allowed to take acetaminophen for fever.
Patients were followed for 28 days. They returned to their respective clinics at two different times for a physical exam, blood tests, urine tests, and respiratory swabs.
The median time to alleviation of symptoms in patients with confirmed influenza was roughly 1 day (21.2 hours) shorter in those who received the larger dose of nitazoxanide than in those who received placebo, a statistically significant difference. The effect of this dosage was comparable to the benefit typical for neuraminidase inhibitor treatment, say the authors.
The 300-mg dose of nitazoxanide reduced the duration of flu symptoms by a median of 7.6 hours in comparison with placebo but this difference was not statistically significant.
Though the 600-mg nitazoxanide dosage was 20% higher and the duration 67% longer than the approved dosage for treatment of intestinal infections, the researchers found no significant change in the side-effect pattern. Also, the frequency and severity of adverse effects didn't vary significantly between any of the three groups in the study.
The researchers said limitations of the study included that the patients were enrolled during a single flu season and that the trial enrolled only60% of the intended number of participants, because of the end of the flu season. They said the next steps are to explore possible benefits in children, severely ill patients, resistant infections, and in combination with other therapies.
In a commentary that accompanied the study, two epidemiology professors from the London School of Hygiene and Tropical Medicine, Krishnan Bhaskaran, MSc, PhD, and Sara Thomas, MBBS, MSc, PhD, wrote that the group's investigation is a welcome attempt to broaden the options for fighting influenza. .
Though the study found benefit in nitazoxanide treatment for relatively healthy flu patients, current guidelines don't typically recommend any treatment in this group, and a bigger benefit could be reducing the burden of flu in vulnerable patients, the two authors wrote. "This recruitment was understandable for an early-stage placebo-controlled study, but because at present trials of high-risk individuals are only at the preparation stage, we will probably have to wait some time to understand the full public health relevance of this drug."
Among other interesting findings were no development of resistance in viral isolates from swabs taken 5 days into treatment and reduction of symptoms in patients in whom no flu virus was ultimately found, which hints at a possible broader use for the drug, the commentators wrote
Bhaskaran and Thomas wrote that a phase 3 trial is under way to look at the possible benefits of combining nitazoxanide with oseltamivir (Tamiflu).
They concluded that the early findings are promising and the drug seems worth pursuing but that the trial was small and the treatment is at an early stage of evaluation, so it's impossible to say now whether nitazoxanide will someday have a role in the fight against flu.
Haffizulla J, Hartman A, Hoppers M, et al. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomized, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis 2014 May 19 [Abstract]
Bhaskaran K, Thomas SL. Fighting influenza—a new weapon in the armoury? (Commentary) Lancet Infect Dis 2014 May 19 [Extract]