Panama and El Salvador Children's Oseltamivir Study

NCT01690637 | Terminated Phase 4 DMC

• 1 other identifier: CDC-NCIRD-6330
• Study Type: interventional
• Target: 721
• Locations: 2 countries
• Sites: 5

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.

Conditions

Influenza; Human Influenza

Keywords

Oseltamivir; Tamiflu

Outcome Measures

Primary Outcomes (3)

• Length of hospitalization

  Day 1 is defined as the day of arrival at the emergency department

  Participants will be followed for the duration of hospital stay, an expected median of 7 days

• Time to resolution of increased work of breathing

  Increased work of breathing is defined as presence of 1 or more of the following: supraclavicular retractions, subcostal or intercostal retractions, nasal flaring, grunting, or need for noninvasive or invasive mechanical ventilation, and resolution is defined as 12 hours or more without increased work of breathing in a child with increased work of breathing at enrollment

  Participants will be followed for the duration of hospital stay, an expected median of 7 days

• Time to resolution of hypoxia

  Hypoxia is defined as O2 saturation less than 92% measured by pulse oximetry while breathing room air or need for noninvasive or invasive mechanical ventilation and resolution is defined as 12 hours or more without hypoxia in a child with hypoxia at enrollment

  Participants will be followed for the duration of hospital stay, an expected median of 7 days

Secondary Outcomes (6)

• Incidence of new onset respiratory failure 24 hours or more after first dose of study medication

  Participants will be followed for the duration of hospital stay, an expected median of 7 days

• Incidence of admission to intensive care unit 24 hours or more after first dose of study medication

  Participants will be followed for the duration of hospital stay, an expected median of 7 days

• Incidence of death 24 hours or more after first dose of study medication

  Participants will be followed up through 7 days after hospital discharge

• Time to non-detectable influenza virus by viral culture and non-detectable influenza viral RNA by RT-PCR

  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

• Proportion of children with oseltamivir resistant virus detected during or after oseltamivir phosphate treatment who had oseltamivir susceptible virus infection at enrollment

  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

Study Arms (2)

Oseltamivir phosphate suspension

ACTIVE COMPARATOR

Participants assigned to the oseltamivir phosphate treatment arm will receive the appropriate weight-based dose of oseltamivir phosphate every 12 hours for 10 doses. For children 0-11 months of age, oseltamivir phosphate will be dosed as 3mg/kg/dose every 12 hours. For children 12 months and older, oseltamivir phosphate will be dosed as follows: 30 mg every 12 hours for children up to 15kg, 45mg every 12 hours for children greater than 15kg up to 23 kg, 60mg every 12 hours for children greater than 23 up to 40kg, and 75mg every 12 hours for children greater than 40kg.

Drug: Oseltamivir phosphate suspension

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Oseltamivir phosphate suspension DRUG

Also known as: Tamiflu

Oseltamivir phosphate suspension

Placebo DRUG

Placebo

Eligibility Criteria

• Age: Up to 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Universidad del Valle, Guatemala: collaborator
• Hospital Nacional San Juan de Dios de Santa Ana, El Salvador: collaborator
• Hospital Nacional San Juan de Dios de San Miguel, El Salvador: collaborator
• Hospital Del Nino, Panama: collaborator
• Hospital de Especialidades Pediátricas Omar Torrijos Herrera, Panama: collaborator
• Hospital Jose Domingo de Obaldia, Panama: collaborator

Study Sites (5)

Hospital Nacional San Juan de Dios de San Miguel

San Miguel, El Salvador

Location

Hospital Nacional San Juan de Dios de Santa Ana

Santa Ana, El Salvador

Location

Hospital Jose Domingo de Obaldia

David, Panama

Location

Hospital de Especialidades Pediátricas Omar Torrijos Herrera

Panama City, Panama

Location

Hospital Del Nino

Panama City, Panama

Location

Related Publications (1)

• 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.

  PMID: 31153920 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Oseltamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Fatimah S Dawood, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

• Jorge Jara, MD

  Universidad del Valle, Guatemala

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Epidemiologist

Study Record Dates

• First Submitted: September 17, 2012
• First Posted: September 24, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: July 1, 2014

Record last verified: 2014-06

Locations

PA (3); EL (2)