Clinical trial NCT02979626: Evaluation of Moderate to Severe Influenza Outcomes in Children
Official title: Evaluation of Moderate to Severe Influenza Disease in Children 6 Months to 8 Years in Colorado
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Influenza
Otitis Media
Lower Resp Tract Infection
Encephalitic Infection
Myositis Viral
Fever
Keywords: hospitalization
intensive care unit
school absenteeism
work absenteeism
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2016-12-01
Enrollment: 1478
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children 6 months to 8 years of age and younger seeking evaluation and management of influenza-like illness (ILI) at any of the study sites will be eligible for participation in the study. The study will commence during the influenza season as determined by the department of microbiology and epidemiology at CHCO (the influenza season commences when there are 3 positive influenza PCR tests within a week), approximately from December 1, 2016 to April 30, 2017.

Brief summary: The purpose of this study was to determine whether moderate-severe endpoints (including high fever, lower respiratory tract disease, acute otitis media, or serious extra-pulmonary complications) were predictive of hospitalization, intensive care admission, antibiotic use and other complications in children under 8 years of age.

Detailed description: This prospective observational study aimed to determine the risk difference of hospitalization due to moderate to severe influenza compared with mild influenza among children aged 6 months to 8 years who were evaluated at Children's Hospital Colorado emergency department and urgent care during the 2016-2017 influenza season. In addition, the study intended to evaluate the risk difference for other health outcomes such as ICU admission, antibiotic and antiviral use, caregiver and child absenteeism and recurrent (\>1) healthcare visits, and to compare the healthcare costs associated with management of moderate to severe versus mild influenza in children. Children who presented to Children's Hospital Colorado Emergency Department (ED) and urgent care affiliated sites (North Campus urgent care) with an influenza-like illness from December 2016 to April 2017 and during the 2016-2017 influenza season, were eligible for the study. Once enrolled in the study, the investigators collected respiratory samples (nasal swab specimens) for influenza testing by PCR, sociodemographic and clinical data including variables of interest outlined above, and followed the clinical outcome of these children for 14 days after their initial presentation. Some of the variables of interest the investigators collected are shown below.

Eligibility criteria: Inclusion Criteria:

* Age 6 months to \< 8 years
* Presentation to one of the study sites with signs and symptoms of influenza-like illness (temperature of \>37.8⁰C and at least one of the following: cough, sore throat, runny nose or nasal congestion)
* Parents or guardians agreeing and consenting to medical information release, respiratory specimen collection and testing, email/phone call follow up and collection of leftover blood samples obtained during routine clinical care
* Patients seen during the 2016-2017 influenza season

Exclusion Criteria:

* Respiratory symptom duration \> 14 days
* Nurse only visit
* Enrollment in the study within prior 14 days

Primary outcomes:
measure: Hospitalization
timeFrame: 0-14 days
Secondary outcomes:
measure: ICU Admission
timeFrame: 0-14 days
measure: Antiviral Use
timeFrame: 0-14 days
measure: Antibiotic Use
timeFrame: 0-14 days
measure: Recurrent Visits
timeFrame: 0-14 days
measure: School Absenteeism
timeFrame: 0-14 days
measure: Work Absenteeism
timeFrame: 0-14 days
Other outcomes:
measure: Injectable Influenza Vaccine (IIV) Hospitalization
timeFrame: 0-14 days
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Broomfield
country: United States
facility: Children's Hospital North Campus Urgent Care
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Edwin J Asturias, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Suchitra Rao, MD
role: STUDY_DIRECTOR
References:
citation: Wilkes JJ, Leckerman KH, Coffin SE, Keren R, Metjian TA, Hodinka RL, Zaoutis TE. Use of antibiotics in children hospitalized with community-acquired, laboratory-confirmed influenza. J Pediatr. 2009 Mar;154(3):447-9. doi: 10.1016/j.jpeds.2008.09.026.
citation: Coffin SE, Zaoutis TE, Rosenquist AB, Heydon K, Herrera G, Bridges CB, Watson B, Localio R, Hodinka RL, Keren R. Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza. Pediatrics. 2007 Apr;119(4):740-8. doi: 10.1542/peds.2006-2679.
citation: Izurieta HS, Thompson WW, Kramarz P, Shay DK, Davis RL, DeStefano F, Black S, Shinefield H, Fukuda K. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med. 2000 Jan 27;342(4):232-9. doi: 10.1056/NEJM200001273420402.
citation: Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000 Jan 27;342(4):225-31. doi: 10.1056/NEJM200001273420401.
citation: Salo H, Kilpi T, Sintonen H, Linna M, Peltola V, Heikkinen T. Cost-effectiveness of influenza vaccination of healthy children. Vaccine. 2006 Jun 5;24(23):4934-41. doi: 10.1016/j.vaccine.2006.03.057. Epub 2006 Apr 7.
citation: Ferdinands JM, Olsho LE, Agan AA, Bhat N, Sullivan RM, Hall M, Mourani PM, Thompson M, Randolph AG; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012. J Infect Dis. 2014 Sep 1;210(5):674-83. doi: 10.1093/infdis/jiu185. Epub 2014 Mar 26.
citation: Heikkinen T, Silvennoinen H, Heinonen S, Vuorinen T. Clinical and socioeconomic impact of moderate-to-severe versus mild influenza in children. Eur J Clin Microbiol Infect Dis. 2016 Jul;35(7):1107-13. doi: 10.1007/s10096-016-2641-9. Epub 2016 Apr 16.
citation: Jain VK, Rivera L, Zaman K, Espos RA Jr, Sirivichayakul C, Quiambao BP, Rivera-Medina DM, Kerdpanich P, Ceyhan M, Dinleyici EC, Cravioto A, Yunus M, Chanthavanich P, Limkittikul K, Kurugol Z, Alhan E, Caplanusi A, Durviaux S, Boutet P, Ofori-Anyinam O, Chandrasekaran V, Dbaibo G, Innis BL. Vaccine for prevention of mild and moderate-to-severe influenza in children. N Engl J Med. 2013 Dec 26;369(26):2481-91. doi: 10.1056/NEJMoa1215817. Epub 2013 Dec 11.
citation: Rao S, Moss A, Lamb M, Innis BL, Asturias EJ. Vital sign predictors of severe influenza among children in an emergent care setting. PLoS One. 2022 Aug 12;17(8):e0272029. doi: 10.1371/journal.pone.0272029. eCollection 2022.
citation: Rao S, Moss A, Lamb MM, Asturias EJ. Evaluation of Influenza Vaccine Effectiveness Among Young Children Receiving Consecutive Versus Nonconsecutive Vaccination During Influenza A(H3N2)-Predominant Seasons. J Pediatric Infect Dis Soc. 2021 Apr 3;10(3):359-362. doi: 10.1093/jpids/piaa080.
citation: Rao S, Yanni E, Moss A, Lamb MM, Schuind A, Bekkat-Berkani R, Innis BL, Cotter J, Mistry RD, Asturias EJ. Evaluation of a New Clinical Endpoint for Moderate to Severe Influenza Disease in Children: A Prospective Cohort Study. J Pediatric Infect Dis Soc. 2020 Sep 17;9(4):460-467. doi: 10.1093/jpids/piz075.