In the Journals

Nitazoxanide not beneficial for treatment of severe acute respiratory illness

Adding nitazoxanide to standard of care for the treatment of children and adults with severe acute respiratory infections was safe, but it did not reduce hospital stay, complications like pneumonia, or the shedding of influenza or other respiratory viruses, according to findings from a double-blind, placebo-controlled trial.

Although severe acute respiratory illnesses (SARIs) are in the top three causes of death and disability among children and adults worldwide, influenza is the only SARI-causing virus to have an effective treatment, noted M. Lourdes Guerrero, MD, MS, from the department of infectious diseases at the National Institute of Medical Sciences and Nutrition Salvador Zubirán in Mexico City, and colleagues.

According to Guerrero and colleagues, in 2012, WHO announced an “urgent need” for new and cost-effective therapies targeting specific respiratory viruses, as well as antivirals with broad-spectrum activity.

“Nitazoxanide (NTZ), in addition to antiparasitic activity, has broad-spectrum in vitro antiviral activity against influenza, [respiratory syncytial virus], norovirus, rotavirus, and hepatitis B and C viruses,” the researchers wrote. “The broad-spectrum antiviral activity of NTZ can be attributed to the fact that it targets host cell mechanisms rather than the virus. In recent studies, NTZ has shown to inhibit replication of a broad range of viruses, including influenza, but not rhinovirus.”

NTZ is approved by the FDA for the treatment of Cryptosporidium infections. Between March 2014 and March 2017, Guerrero and colleagues enrolled 260 participants aged 1 year or older who were hospitalized at six tertiary-care hospitals in Mexico with influenza-like illness in a double-blind, placebo-controlled trial. Of those, 257 participants received standard of care and were randomly assigned to also receive either NTZ or placebo for 5 days.

All age groups were dosed twice daily. Participants aged 12 years or older were given 600 mg, children aged 4 to 11 years were given 200 mg and children aged 1 to 3 years were given 100 mg. The primary end point was time from first dose to hospital discharge, according to the study.

The NTZ group consisted of 130 patients, with a median duration of hospitalization of 6.5 days compared with 7 days in the placebo group, which had 127 patients (P = .56). Guerrero and colleagues found that the duration of hospitalization between the two treatments was similar not only in adults (P = .62) and children (P = .29), but also in patients with influenza A and B (P = .32) and other respiratory viruses. They reported that 5.4% of participants in the NTZ group reported severe adverse events compared with 4.7% in the placebo group.

Even when the researchers conducted further analyses based on age and virus type, they found no benefit from NTZ.

“In this trial, treatment with nitazoxanide was safe in children and adults, but failed to show benefit in reducing duration of hospitalization or other endpoints in severe influenza-like illness,” Guerrero and colleagues concluded. “The totality of the evidence from all performed trials with NTZ should be evaluated prior to additional studies being commenced with this molecule in respiratory viral diseases.” - by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.

Adding nitazoxanide to standard of care for the treatment of children and adults with severe acute respiratory infections was safe, but it did not reduce hospital stay, complications like pneumonia, or the shedding of influenza or other respiratory viruses, according to findings from a double-blind, placebo-controlled trial.

Although severe acute respiratory illnesses (SARIs) are in the top three causes of death and disability among children and adults worldwide, influenza is the only SARI-causing virus to have an effective treatment, noted M. Lourdes Guerrero, MD, MS, from the department of infectious diseases at the National Institute of Medical Sciences and Nutrition Salvador Zubirán in Mexico City, and colleagues.

According to Guerrero and colleagues, in 2012, WHO announced an “urgent need” for new and cost-effective therapies targeting specific respiratory viruses, as well as antivirals with broad-spectrum activity.

“Nitazoxanide (NTZ), in addition to antiparasitic activity, has broad-spectrum in vitro antiviral activity against influenza, [respiratory syncytial virus], norovirus, rotavirus, and hepatitis B and C viruses,” the researchers wrote. “The broad-spectrum antiviral activity of NTZ can be attributed to the fact that it targets host cell mechanisms rather than the virus. In recent studies, NTZ has shown to inhibit replication of a broad range of viruses, including influenza, but not rhinovirus.”

NTZ is approved by the FDA for the treatment of Cryptosporidium infections. Between March 2014 and March 2017, Guerrero and colleagues enrolled 260 participants aged 1 year or older who were hospitalized at six tertiary-care hospitals in Mexico with influenza-like illness in a double-blind, placebo-controlled trial. Of those, 257 participants received standard of care and were randomly assigned to also receive either NTZ or placebo for 5 days.

All age groups were dosed twice daily. Participants aged 12 years or older were given 600 mg, children aged 4 to 11 years were given 200 mg and children aged 1 to 3 years were given 100 mg. The primary end point was time from first dose to hospital discharge, according to the study.

The NTZ group consisted of 130 patients, with a median duration of hospitalization of 6.5 days compared with 7 days in the placebo group, which had 127 patients (P = .56). Guerrero and colleagues found that the duration of hospitalization between the two treatments was similar not only in adults (P = .62) and children (P = .29), but also in patients with influenza A and B (P = .32) and other respiratory viruses. They reported that 5.4% of participants in the NTZ group reported severe adverse events compared with 4.7% in the placebo group.

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Even when the researchers conducted further analyses based on age and virus type, they found no benefit from NTZ.

“In this trial, treatment with nitazoxanide was safe in children and adults, but failed to show benefit in reducing duration of hospitalization or other endpoints in severe influenza-like illness,” Guerrero and colleagues concluded. “The totality of the evidence from all performed trials with NTZ should be evaluated prior to additional studies being commenced with this molecule in respiratory viral diseases.” - by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.