Clinical trial NCT01690637: Panama and El Salvador Children's Oseltamivir Study
Official title: Efficacy of Early Oseltamivir Phosphate Treatment at Hospital Admission to Reduce Severity of Illness Among Children Aged Less Than 10 Years Hospitalized With Influenza in El Salvador and Panama
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Influenza
Human Influenza
Keywords: Oseltamivir
Tamiflu
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: Universidad del Valle, Guatemala
name: Hospital Nacional San Juan de Dios de Santa Ana, El Salvador
name: Hospital Nacional San Juan de Dios de San Miguel, El Salvador
name: Hospital Del Nino, Panama
name: Hospital de Especialidades Pediátricas Omar Torrijos Herrera, Panama
name: Hospital Jose Domingo de Obaldia, Panama
First posted: 2012-09-24
Enrollment: 721
Sex: ALL
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized, double-blind, placebo-controlled trial that will be conducted in tertiary care pediatric hospitals in El Salvador and Panama. The primary purpose of this study is to determine whether empiric oseltamivir phosphate treatment given at the time of hospital admission to children less than 10 years of age hospitalized with influenza can effectively reduce their illness severity. Additional objectives are to: 1) evaluate the tolerability of oseltamivir phosphate treatment, 2) evaluate the effect of oseltamivir treatment on viral clearance and development of oseltamivir-resistant influenza virus during and after treatment in children hospitalized with influenza, 3) estimate the direct and indirect costs of all-cause respiratory illness and influenza-associated respiratory illness requiring hospitalization, and 4) evaluate the effect of empiric oseltamivir treatment during the influenza season on these costs.

The primary study hypothesis is that children with laboratory-confirmed influenza receiving empiric oseltamivir phosphate treatment initiated at the time of hospital admission will have a shorter duration of hospitalization and a shorter time to resolution of signs of severe respiratory illness compared to children receiving placebo. The secondary study hypotheses are that children with laboratory-confirmed influenza receiving oseltamivir phosphate treatment will have a reduction in the time to non-detectable influenza virus and influenza viral RNA and children with all-cause respiratory illness receiving oseltamivir phosphate will not be more likely to experience severe adverse events than children receiving placebo.


Eligibility criteria: Inclusion Criteria:

* Age \<10 years
* Accompanied by a parent or guardian who has the capacity to grant and sign the written informed consent and who has consented to enrollment
* Has respiratory illness as defined by modified IMCI criteria for pneumonia:
* Cough or sore throat AND Fast breathing, defined as respiratory rate 60 breaths per minutes or greater for children 0 to \<2 months, OR respiratory rate 50 breaths per minute or greater for children 2 to \<12 months, OR respiratory rate 40 breaths per minute or greater for children 12 to \<60 months, OR respiratory rate 30 breaths per minute or greater for children 5-9 years
* Planned for hospital admission

Exclusion Criteria:

* Symptom onset 7 days or more at the time of study screening where day 1 is the day of symptom onset
* Concomitant severe vomiting illness prior to enrollment that would preclude ability to take medication orally defined as more than 3 vomiting episodes in the preceding 24 hours
* Prematurity (birth at less than 37 weeks gestation) for children aged less than 3 months
* Birth weight less than 2500 grams for children aged less than 3 months
* Chronic supplemental oxygen requirement at home
* Known history of renal dysfunction
* History of gastrointestinal resection resulting in gastrointestinal abnormality that might hinder absorption of oral medication (such as short-gut syndrome)
* History of previous serious adverse reaction to oseltamivir phosphate
* Receipt of oseltamivir phosphate during the 5 days prior to presentation at the admitting hospital
* Previous enrollment in this study during a hospitalization that ended less than 14 days prior to the current admission

Primary outcomes:
measure: Length of hospitalization
timeFrame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
measure: Time to resolution of increased work of breathing
timeFrame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
measure: Time to resolution of hypoxia
timeFrame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
Secondary outcomes:
measure: Incidence of new onset respiratory failure 24 hours or more after first dose of study medication
timeFrame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
measure: Incidence of admission to intensive care unit 24 hours or more after first dose of study medication
timeFrame: Participants will be followed for the duration of hospital stay, an expected median of 7 days
measure: Incidence of death 24 hours or more after first dose of study medication
timeFrame: Participants will be followed up through 7 days after hospital discharge
measure: Time to non-detectable influenza virus by viral culture and non-detectable influenza viral RNA by RT-PCR
timeFrame: Participants will be followed for the duration of hospital stay (an expected median of 7 days) or up through 21 days of hospitalization, whichever is shorter
measure: Proportion of children with oseltamivir resistant virus detected during or after oseltamivir phosphate treatment who had oseltamivir susceptible virus infection at enrollment
timeFrame: Participants will be followed for the duration of hospital stay (an expected median of 7 days) or up through 21 days of hospitalization, whichever is shorter
measure: Proportion of participants experiencing adverse events (including severe and non-severe)
timeFrame: Up through 7 days after hospital discharge
Other outcomes:
Locations:
city: San Miguel
country: El Salvador
facility: Hospital Nacional San Juan de Dios de San Miguel
city: Santa Ana
country: El Salvador
facility: Hospital Nacional San Juan de Dios de Santa Ana
city: David
country: Panama
facility: Hospital Jose Domingo de Obaldia
city: Panama City
country: Panama
facility: Hospital de Especialidades Pediátricas Omar Torrijos Herrera
city: Panama City
country: Panama
facility: Hospital Del Nino
Study officials:
affiliation: Centers for Disease Control and Prevention
name: Fatimah S Dawood, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad del Valle, Guatemala
name: Jorge Jara, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jara JH, Azziz-Baumgartner E, De Leon T, Luciani K, Brizuela YS, Estripeaut D, Castillo JM, Barahona A, Corro M, Cazares R, Vergara O, Rauda R, Gonzalez R, Franco D, Widdowson MA, Clara W, Alvis-Estrada JP, Murray CT, Ortega-Sanchez IR, Dawood FS. Costs associated with acute respiratory illness and select virus infections in hospitalized children, El Salvador and Panama, 2012-2013. J Infect. 2019 Aug;79(2):108-114. doi: 10.1016/j.jinf.2019.05.021. Epub 2019 May 31.