Clinical Immunization Safety Assessment (CISA) Project: Pilot Study to Assess the Effect of Prophylactic Antipyretics on Immune Responses and Fever After IIV

NCT ID: NCT01946594

Last Updated: 2016-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2014-03-31

Brief Summary

The study team aims to conduct a double-blind, placebo-controlled, pilot study to assess the effect of prophylactic antipyretics on the immune responses and rates of fever after inactivated influenza vaccine (IIV) in children 12 through 35 months of age. In this pilot, 40 healthy children, 12 through 35 months of age, including some children at risk of febrile seizure, will be randomized to receive prophylactic acetaminophen or oral placebo immediately following and every 4 to 6 hours in the 24 hours after receipt of a dose of IIV. Data derived from the pilot study will be used to assess the feasibility of conducting a larger scale study. Feasibility will include assessments of the speed and ease of study recruitment and adherence to and completion of study assessments. 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 day following vaccination. Antibody to influenza antigens contained in the 2013-2014 vaccine 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 reactions, 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 receiving acetaminophen and placebo. Likewise geometric mean HAI titers (GMT) and corresponding 95% confidence intervals for each IIV antigen will be calculated for both vaccine groups.

Conditions

Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Acetaminophen Arm

Acetaminophen Suspension 160 mg / 5 mL:

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

Group Type: ACTIVE_COMPARATOR

Acetaminophen

Intervention Type: OTHER

Placebo Arm

Placebo Suspension:

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Interventions

Acetaminophen

Intervention Type: OTHER

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

To be eligible for inclusion in the study the following enrollment criteria must be met:

1. The child must be 12 through 35 months of age.

2. The child must only need a single dose of IIV during the current season. (Children only need 1 dose of vaccine in 2013-14 if they received a total of 2 or more doses of seasonal vaccine since July 1, 2010. Children who did not receive a total of 2 or more doses of seasonal vaccine since July 1, 2010 require 2 doses in 2013-14).[19]

3. The parent/guardian must be willing and capable of providing written informed consent for the child.

4. The parent/guardian must be available for follow-up and must at minimum have telephone access.

5. 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).

Exclusion Criteria

Participants must not have any of the following:

1. History of receipt of current year's licensed influenza vaccine.

2. 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.

3. History of a severe allergic reaction (e.g. anaphylaxis) following a prior dose of influenza vaccine.

4. History of an allergic reaction following acetaminophen or ingredients in the acetaminophen product.

5. History of an allergic reaction following ibuprofen or ingredients in the ibuprofen product.

6. History of liver disease.

7. Currently taking the blood thinning drug warfarin (Coumadin).

8. 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 vaccination in this study. Concomitant vaccinations are not allowed.

9. 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 receipt of the influenza vaccine.

10. 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).

11. A moderate to severe acute illness and/or a reported temperature greater than or equal to 100.0°F (37.8°C) within 72 hours prior to first dose of IIV or an axillary temperature greater than or equal to 100.0°F (37.8°C) at the time of enrollment. (This may result in a temporary delay of vaccination).

12. Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 72 hours prior to the first dose of IIV (This may result in a temporary delay of vaccination) or is already planning to administer a prophylactic antipyretic medication on the day of and the day following IIV (this exclusion does not apply if the caretaker indicates he/she might administer antipyretics after vaccination to reduce a fever).

13. Immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months.

14. Long term (at least 14 days of prednisone 2 mg/kg/day or equivalent other glucocorticoid), any parenteral steroids, high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (topical and nasal steroids are allowed).

15. History of Guillain-Barré syndrome within 6 weeks of a prior dose of influenza vaccine.

16. Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 35 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel B Walter, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Karen Broder, MD

Role: PRINCIPAL_INVESTIGATOR

Centers for Disease Control and Prevention

Locations

Duke University Health System

Durham, North Carolina, United States

Countries

United States

Other Identifiers

200-2012-53663

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Pro00048541

Identifier Type: -

Identifier Source: org_study_id