The Effect of Prophylactic Antipyretics on Immune Responses and Fever After 2014-2015 and 2015-2016 Inactivated Influenza Vaccine

NCT02212990 | Completed

• 2 other identifiers: Pro00056213200-2012-53663
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to conduct a double-blind, placebo-controlled study to assess the effect of prophylactic antipyretics on the immune responses and rates of fever after inactivated influenza vaccine (IIV) in children 6 through 47 months of age. In this study, 160 healthy children, 6 through 47 months of age, including some children at risk of febrile seizure, will be randomized to one of three different treatment arms. Children will receive either blinded therapy with prophylactic acetaminophen or placebo immediately following and every 4 to 6 hours in the 24 hours after receipt of a dose of IIV or open-label ibuprofen every 6 to 8 hours in the 24 hours after receipt of a dose of IIV. Children will be followed for the occurrence of fever, fussiness, changes in appetite and sleep patterns, and use of medical services on the day of and for two days following vaccination. Antibody to influenza antigens contained in the respective 2014-2015 and 2015-2016 vaccines as measured by hemagglutination inhibition (HAI) antibody will be assessed at baseline and four weeks following vaccination. The proportions of children experiencing fever, having solicited side effects, using medical services, demonstrating a serologic response corresponding to seroprotection and seroconversion to each of the IIV antigens will be determined for groups of children in each of the three treatment arms. Likewise geometric mean HAI titers (GMTs) and corresponding 95% confidence intervals for each IIV antigen will be calculated for the three treatment arms. The investigators hope to learn whether or not prophylactic antipyretics affect the immune response and fever rates following IIV.

Conditions

Fever

Keywords

Fever; Antipyretics; Acetaminophen; Ibuprofen; Influenza vaccine; Influenza; Body temperature changes; Signs and symptoms

Outcome Measures

Primary Outcomes (1)

• Seroconversion

  Seroconversion (an HAI titer ≥ 1:40 four weeks post- vaccination if the baseline titer is \< 1:10 or a four-fold rise in HAI titer if the baseline titer is ≥ 1:10) for each IIV antigen

  One month following the last dose of IIV

Secondary Outcomes (2)

• Seroprotection

  One month following the last dose of IIV

• Geometric mean HAI titer

  One month following the last dose of IIV

Other Outcomes (3)

• Fever

  Days 0, 1, and 2 following IIV

• Systemic symptoms following IIV

  Days 0, 1, and 2 following IIV

• Receipt of medical attention

  Days 0, 1, and 2 following IIV

Study Arms (3)

Acetaminophen Arm

ACTIVE COMPARATOR

Acetaminophen Suspension 160mg / 5mL Oral dose immediately following IIV and every 4 to 6 hours up to 24 hours (Maximum 5 oral doses)

Other: Acetaminophen Arm

Placebo Arm

PLACEBO COMPARATOR

Placebo Suspension Oral dose immediately following IIV and every 4 to 6 hours up to 24 hours (Maximum 5 oral doses)

Other: Placebo Arm

Ibuprofen Arm

ACTIVE COMPARATOR

Ibuprofen Suspension 100mg / 5mL Oral dose immediately following IIV and every 6 to 8 hours up to 24 hours (Maximum 4 oral doses)

Other: Ibuprofen Arm

Interventions

Acetaminophen Arm OTHER

Blinded Therapy

Acetaminophen Arm

Placebo Arm OTHER

Blinded Therapy

Placebo Arm

Ibuprofen Arm OTHER

Open Label Therapy

Ibuprofen Arm

Eligibility Criteria

• Age: 6 Months - 47 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• The child must be 6 through 47 months of age.
• The child must weigh 5.4 kilograms.
• The child must be receiving IIV this season.
• If the child is two years of age or older and needs two doses of influenza vaccine this season the parent/guardian intends for the child to receive IIV for the second dose.
• The parent/guardian must be willing and capable of providing written informed consent for the child.
• The parent/guardian must be available for follow-up and must at minimum have telephone access.
• The parent/guardian must agree to sign a medical release for the child so that study personnel may obtain medical information about the child's health (if needed).

You may not qualify if:

• History of receipt of current year's licensed influenza vaccine.
• Planned receipt of the live attenuated nasally administered influenza vaccine this year
• History of a severe allergic reaction (e.g. anaphylaxis) to any component of influenza vaccine, including egg protein, formaldehyde, octylphenol ethoxylate, gelatin, or thimerosal if using thimerosal containing vaccine.
• History of a severe allergic reaction (e.g. anaphylaxis) following a prior dose of influenza vaccine.
• History of an allergic reaction following acetaminophen or ingredients in the acetaminophen product.
• History of an allergic reaction following ibuprofen or ingredients in the ibuprofen product.
• History of an allergic reaction following aspirin or other pain reliever or fever reducer.
• History of liver disease.
• Currently taking the blood thinning drug warfarin (Coumadin) or other blood thinners.
• History of recent or planned heart surgery within the past 3 months or next 3 months.
• History of stomach ulcer or bleeding problem.
• Currently already routinely taking prescription or nonprescription non-steroidal anti-inflammatory drugs or NSAIDs (aspirin, ibuprofen, naproxen, or others)
• Received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to vaccination in this study or expects to receive a licensed vaccine during the 28 days following the last influenza vaccination in this study. Concomitant vaccinations are not allowed.
• Routine immunizations are delayed or will be delayed by not being able to receive a concomitantly administered vaccine or a needed vaccine in the 28 days following the last influenza vaccination in this study.
• Received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to vaccination in this study, or expects to receive an experimental/investigational agent within the follow-up time period (28 days after the last vaccination in this study).

Sponsors & Collaborators

• Duke University: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Fever; Influenza, Human; Body Temperature Changes; Signs and Symptoms

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Emmanuel B Walter, MD, MPH

  Duke Unviersity School of Medicine

  PRINCIPAL INVESTIGATOR

• Karen Broder, MD

  Centers for Diseaes Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 11, 2014
• Study Start: September 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: February 7, 2018

Record last verified: 2016-04

Locations

US (1)