Virological Clearance Rate of High-Dose Oseltamivir or Triple-Combination Antiviral Therapy in Complicated 2009 Pandemic Influenza A (H1N1) Infection

Kang, Seung-Ji; Park, Kyung‐Hwa; Kee, Seung‐Jung; Shin, Jong‐Hee; Jung, Sook-In; Kwon, Yong Soo; Jang, Hee Chang

doi:10.7883/yoken.66.425

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…A third study retrospective review of 6 patients with severe H1N1 treated with combination antivirals, and compared to 8 patients treated with high-dose oseltamivir. 24 The clinical outcomes and viral shedding was not significantly different in the treatment arm.…”

Section: Figurementioning

confidence: 86%

“…Another retrospective review of 14 patients with complicated H1N1 influenza compared the viral shedding seen in high-dose oseltamivir (150 mg twice a day) in 8 patients to 6 patients treated with combination antiviral drugs (150 mg oseltamivir twice a day, 100 mg amantadine twice a day, and 300 mg ribavirin three times a day). 24 The authors concluded that combination antivirals could be useful to achieve virologic clearance, though viral shedding after 5 days was seen in 1 of 6 participants treated with oseltamivir monotherapy, and 2 of 6 of those treated with combination antivirals.…”

Section: Discussionmentioning

confidence: 99%

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Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial

Beigel¹,

Bao²,

Beeler³

et al. 2017

The Lancet Infectious Diseases

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Summary Background Influenza continues to have a significant socioeconomic and health impact despite a long established vaccine program and approved antivirals. Preclinical data suggest combination antivirals might be more effective than oseltamivir alone in the treatment of influenza. Methods We conducted a randomized, double-blinded, multicenter phase 2 trial of combination antivirals versus monotherapy for the treatment of influenza. Participants ≥18 years with influenza at increased risk of complications from influenza were randomized by an online computer-generated randomization system to receive either oseltamivir, amantadine, and ribavirin or oseltamivir alone for 5 days, and followed for 28 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at Day 3. Among the secondary outcomes, there were safety and time to alleviation of influenza clinical symptoms. ClinicalTrials.gov Identifier: NCT01227967. Findings Between March 2011 and April 2016 we randomized 633 participants. Seven participants were excluded from analysis: 3 were given treatment without randomization, 3 withdrew before taking any medication, and 1 was lost to follow-up. The primary analysis included 394 participants, excluding 47 in the pilot phase, 172 without confirmed influenza, and 13 without an endpoint sample. 80 of 200 (40.0%) participants in the combination arm had virus detectable at Day 3 compared to 97 of 194 (50.0%) (95%C.I. 0.2–19.8%, p=0.046) in the control arm. There was no benefit, however, in multiple clinical secondary endpoints, such as median duration of symptoms (4.5 days in the combination arm vs 4.0 days in the oseltamivir arm; p = 0.21). Interpretation Although oseltamivir, amantadine, and ribavirin showed a statistically significant decrease in viral shedding at Day 3 relative to oseltamivir, this difference was not associated with improved clinical benefit. More work is needed to understand the lack of clinical benefit when a difference in virologic outcome was identified. Funding National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States.

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Section: Figurementioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial

Beigel¹,

Bao²,

Beeler³

et al. 2017

The Lancet Infectious Diseases

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“…Luo et al reported an adult case of severe RSV infection progressing to ARDS that was successfully treated with inhaled ribavirin (137), but overall effectiveness in treatment of viral pediatric ARDS has yet to be determined. In addition to its use in RSV, ribavirin has also been used in treatment of severe influenza A (H1N1) virus infection (138). Ribavirin can be given orally but is typically aerosolized when used for respiratory viral infections.…”

Section: Treatment Options Available For Rsv and Influenza A (H1n1) Vmentioning

confidence: 99%

Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome

2016

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Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.

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“…Kim et al [10] reported that an oseltamivir administration at a high dose, which was two times more than the standard dose, showed a clinical improvement in a pediatric severe influenza patient who had a graft-versus-host disease. Kang et al [11] evaluated the therapeutic reactions of high dose oseltamivir treatment in severe adult patients who were infected by the pandemic influenza in 2009 and reported that six out of the eight severe patients with accompanying pneumonia survived and no virus was detected in five out of the six surviving patients on the fifth day after starting the treatment.…”

Section: Antiviral Agentsmentioning

confidence: 99%

Severe Influenza Treatment Guideline

et al. 2014

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Virological Clearance Rate of High-Dose Oseltamivir or Triple-Combination Antiviral Therapy in Complicated 2009 Pandemic Influenza A (H1N1) Infection

Cited by 8 publications

References 21 publications

Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial

Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial

Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome

Severe Influenza Treatment Guideline

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