Dataset Information

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

ABSTRACT:

Background

Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding.

Methods

From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study. Eligible participants were randomized to receive oseltamivir 75 mg or placebo twice daily for 5 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at day 3.

Results

Of 716 adults screened for the study, 558 were randomized, and 501 were confirmed to have influenza. Forty-six participants in the pilot study were excluded, and 449 of the 455 participants in the population for the primary analysis had day 3 viral shedding results. Ninety-nine (45.0%) of 220 participants in the oseltamivir arm had virus detected at day 3 compared with 131 (57.2%) of 229 participants in the placebo arm (absolute difference of -12.2% [-21.4%, -3.0%], P =; .010). The median time to alleviation of symptoms was 79.0 hours for the oseltamivir arm and 84.0 hours for the placebo arm (P =; .34) in those with confirmed influenza infection.

Conclusions

Oseltamivir decreased viral shedding in this low-risk population. However, in the population enrolled in this study, it did not significantly decrease the time to resolution of clinical symptoms.

Clinical trials registration

NCT01314911.

SUBMITTER: Beigel JH

PROVIDER: S-EPMC7245154 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

Beigel John H JH Manosuthi Weerawat W Beeler Joy J Bao Yajing Y Hoppers Melanie M Ruxrungtham Kiat K Beasley Richard L RL Ison Michael M Avihingsanon Anchalee A Losso Marcelo H MH Langlois Nicholas N Hoopes Justin J Lane H Clifford HC Holley H Preston HP Myers Christopher A CA Hughes Michael D MD Davey Richard T RT

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200501 11

<h4>Background</h4>Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding.<h4>Methods</h4>From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the stud ...[more]

PMID: 31541242

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Project description:ObjectiveTo investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza.DesignDouble blind randomised trial.SettingThirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam.ParticipantsPatients aged ≥ 1 year admitted to hospital with confirmed severe influenza.InterventionsOral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent).Main outcome measureViral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five.ResultsOf 326 patients (including 246 (75.5%) children aged <15), 165 and 161 were randomised to double or standard dose oseltamivir, respectively. Of these, 260 (79.8%) were infected with influenza virus A (133 (40.8%) with A/H3N2, 72 (22.1%) with A/H1N1-pdm09, 38 (11.7%) with seasonal A/H1N1, 17 (5.2%) with A/H5N1) and 53 (16.2%) with influenza virus B. A further 3.9% (13) were false positive by rapid antigen test (negative by RT-PCR and no rise in convalescent haemagglutination inhibition titers). Similar proportions of patients were negative for RT-PCR on day five of treatment: 115/159 (72.3%, 95% confidence interval 64.9% to 78.7%) double dose recipients versus 105/154 (68.2%, 60.5% to 75.0%) standard dose recipients; difference 4.2% (-5.9 to 14.2); P=0.42. No differences were found in clearance of virus in subgroup analyses by virus type/subtype, age, and duration of illness before randomisation. Mortality was similar: 12/165 (7.3%, 4.2% to 12.3%) in double dose recipients versus 9/161 (5.6%, 3.0% to 10.3%) in standard dose recipients. No differences were found between double and standard dose arms in median days on supplemental oxygen (3 (interquartile range 2-5) v 3.5 (2-7)), in intensive care (4.5 (3-6) v 5 (2-11), and on mechanical ventilation (2.5 (1-16) v 8 (1-16)), respectively. No important differences in tolerability were found.ConclusionsThere were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital.RegistrationClinical Trials NCT00298233.

Project description:BackgroundEchinacea has antiviral activity against influenza viruses in vitro and has traditionally been used for treatment of colds and flu.ObjectivesThis randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new echinacea formulation with the neuraminidase inhibitor oseltamivir, the gold standard treatment for influenza.MethodsFollowing informed consent, 473 patients with early influenza symptoms (≤48 hours) were recruited in primary care in the Czech Republic and randomized to either 5 days of oseltamivir followed by 5 days of placebo, or 10 days of an Echinacea purpurea-based formulation called Echinaforce Hotdrink (A. Vogel Bioforce AG, Roggwil, Switzerland). The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for noninferiority between treatment groups using a generalized Wilcoxon test with significance level α = 0.05 (2-sided) and using a CI approach in the per-protocol sample.ResultsRecovery from illness was comparable in the 2 treatment groups at 1.5% versus 4.1% after 1 day, 50.2% versus 48.8% after 5 days, and 90.1% versus 84.8% after 10 days of treatment with Echinaforce Hotdrink and oseltamivir, respectively. Noninferiority was demonstrated for each day and overall (95% CI, 0.487-0.5265 by generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce Hotdrink than with oseltamivir (2.46% vs 6.45%; P = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink.ConclusionsEchinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive treatment option, particularly suitable for self-care. Clinical trial identifier: Eudra-CT: 2010-021571-88. (Curr Ther Res Clin Exp. 2015; 77:66-72).

Project description:BackgroundQuality of life outcomes have been used frequently in clinical trials of oral health interventions. This study assessed the effects of a randomized trial on oral health related quality of life comparing an individual-based oral hygiene intervention to a community-based intervention.MethodsParticipants were recruited from six low-income senior housing residences. Buildings were randomly assigned to receive the individual-based intervention followed by the community-based intervention or to receive the community-based intervention followed by the individual intervention. Participants' oral hygiene was assessed at baseline (T0), one month after the first intervention (T1) and one month after the second intervention (T2) and six months after the T2 assessment (T3). Oral hygiene was measured by the Gingival Index (GI) and Plaque scores (PS). Surveys collected data on beliefs, attitudes, behaviors and self-reported health status at T0, T1 and T2. Only oral hygiene and quality of life, measured by the General Oral Health Assessment Index (GOHAI), was assessed at all time points. general linear mixed models (GLMM) were used to assess changes in GOHAI over time, the interaction of condition by time and the contribution of psychosocial, behavioral, health status and background variables to changes in GOHAI.Results331 people completed T0 assessments; 306 completed T1; 285 completed T2 and 268 completed T3. Scores on GOHAI at T0 ranged from 10 to 48 with a mean of 39.7 (sd = 7.8) and a median of 42. At T1, mean GOHAI was 40.7 (sd = 8.2), at T2 mean GOHAI was 41.1 (sd = 7.8) and at T3, GOHAI was 42.3 (sd = 8.2). GLMM showed that GOHAI improved significantly from T0 to T3 (p = 0.01) but the time by intervention interaction was not significant indicating that both interventions were effective in improving GOHAI but one intervention was not better than the other. Ethnicity, health status, worries, self-efficacy, number of missing teeth and symptoms of dry mouth were related to improvements in GOHAI. Neither GI nor PS were related to GOHAI.ConclusionsThe participants reported relatively good oral health related quality of life which improved significantly over time. Improvement occurred among all participants regardless of condition, suggesting that either intervention would be effective in future studies.Trial registryClinicaltrials.gov, Clinical Trials ID #NCT02419144; Title: A Bi-level Intervention to Improve Older Adult Oral Health Status; Registered 04/07/2015 URL: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005H9X&selectaction=Edit&uid=U0000KBK&ts=2&cx=-rajj5q.

Project description:Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo.We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008-2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ, ?=192; O, n=176; Z, n=173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n=157), O (n=141), and Z (n=149) arms had RT-PCR<200 cgeq/µl (-13.0%, 95% confidence interval [CI] -23.1 to -2.9, p=0.025; +12.3%, 95% CI 2.39-22.2, p=0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p=0.060, p=0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0-4.0, p=0.018; +0.0, 95% CI -3.0 to 3.0, p=0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n=13; O, n=4; and Z, n=5 patients, respectively).In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice.www.ClinicalTrials.govNCT00799760.

Project description:ImportanceGuidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.ObjectiveTo evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression.Design, setting, and participantsThe Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred.InterventionsPatients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.Main outcomes and measuresThe primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years.ResultsAfter randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2.5%-17.9%]; P = .02).Conclusions and relevanceAmong patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.Trial registrationclinicaltrials.gov Identifier: NCT01560052.

Project description:ImportanceDisability among older adults is a strong predictor of health outcomes, health service use, and health care costs. Few interventions have reduced disability among older adults.ObjectiveTo determine whether a 10-session, home-based, multidisciplinary program reduces disability.Design, setting, and participantsIn this randomized clinical trial of 300 low-income community-dwelling adults with a disability in Baltimore, Maryland, between March 18, 2012, and April 29, 2016, 65 years or older, cognitively intact, and with self-reported difficulty with 1 or more activities of daily living (ADLs) or 2 or more instrumental ADLs (IADLs), participants were interviewed in their home at baseline, 5 months (end point), and 12 months (follow-up) by trained research assistants who were masked to the group allocation. Participants were randomized to either the intervention (CAPABLE) group (n = 152) or the attention control group (n = 148) through a computer-based assignment scheme, stratified by sex in randomized blocks. Intention-to-treat analysis was used to assess the intervention. Data were analyzed from September 2017 through August 2018.InterventionsThe CAPABLE group received up to 10 home visits over 5 months by occupational therapists, registered nurses, and home modifiers to address self-identified functional goals by enhancing individual capacity and the home environment. The control group received 10 social home visits by a research assistant.Main outcomes and measuresDisability with ADLs or IADLs at 5 months. Each ADL and IADL task was self-scored from 0 to 2 according to whether in the previous month the person did not have difficulty and did not need help (0), did not need help but had difficulty (1), or needed help regardless of difficulty (2). The overall score ranged from 0 to 16 points.ResultsOf the 300 people randomized to either the CAPABLE group (n = 152) or the control group (n = 148), 133 of the CAPABLE participants (87.5%) were women with a mean (SD) age of 75.7 (7.6) years; 126 (82.9%) self-identified as black. Of the controls, 129 (87.2%) were women with a mean (SD) age of 75.4 (7.4) years; 133 (89.9%) self-identified as black. CAPABLE participation resulted in 30% reduction in ADL disability scores at 5 months (relative risk [RR], 0.70; 95% CI, 0.54-0.93; P = .01) vs control participation. CAPABLE participation resulted in a statistically nonsignificant 17% reduction in IADL disability scores (RR, 0.83; 95% CI, 0.65-1.06; P = .13) vs control participation. Participants in the CAPABLE group vs those in the control group were more likely to report that the program made their life easier (82.3% vs 43.1%; P < .001), helped them take care of themselves (79.8% vs 35.5%; P < .001), and helped them gain confidence in managing daily challenges (79.9% vs 37.7%; P < .001).Conclusions and relevanceLow-income community-dwelling older adults who received the CAPABLE intervention experienced substantial decrease in disability; disability may be modifiable through addressing both the person and the environment.Trial registrationClinicalTrials.gov identifier: NCT01576133.

Dataset Information

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial.

Similar Datasets

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