Comparison of Full-dose Flu Vaccine to Half-dose Flu Vaccine

• Sponsor: U.S. Army Medical Research and Development Command (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00283283
• Collaborator: Walter Reed Army Medical Center (U.S. Fed), United States Army Medical Materiel Development Activity (U.S. Fed), Centers for Disease Control and Prevention (U.S. Fed), Uniformed Services University of the Health Sciences (U.S. Fed), Walter Reed Army Institute of Research (WRAIR) (U.S. Fed), U.S. Air Force Office of the Surgeon General (U.S. Fed)
• Enrollment: 1,316
• Locations: 2
• Arms: 8
• Actual Duration (Months): 17.9
• Patients Per Site: 658
• Patients Per Site Per Month: 36.7

Study Details

Study Description

Brief Summary

This study compared full-dose Flu vaccine to half-dose Flu-vaccine during the 2004-2005 flu season.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine)	Phase 2

Detailed Description

This was a Phase II prospective, single-blind to dose, randomized study that compared the immunogenicity of subjects receiving half-dose Fluzone® compared to full-dose Fluzone®, 2004-2005 formulation. 1440 healthy subjects, ages 18-64 years old and not currently indicated for influenza vaccination under the interim ACIP guidelines, were divided into 8 strata based on age, gender, and previous exposure to influenza vaccine, and randomized to receive either half-dose (0.25mL) Fluzone® or full-dose (0.5mL) Fluzone® by intramuscular injection into the deltoid muscle.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1316 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Clinical Study to Compare the Immune Response of Half Dose Trivalent Inactivated Influenza Vaccine (TIV) to Full Dose
• Actual Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Nov 1, 2004
• Actual Study Completion Date: May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Male, Age 18 -49, Full Dose 0.5ml, 15µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Experimental: Male, Age 50 -64, Half Dose 0.25ml, 7.5µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinia per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Experimental: Female, Age 18 - 49, Full Dose 0.5ml, 15µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Experimental: Female, Age 18 - 49, Half Dose 0.25ml, 7.5µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinia per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Experimental: Male, Age 18 - 49, Half Dose 0.25ml, 7.5µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinia per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Experimental: Male, Age 50 -64, Full Dose 0.5ml, 15µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Experimental: Female, Age 50 -64, Full Dose 0.5ml, 15µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Experimental: Female, Age 50 -64, Half Dose 0.25ml, 7.5µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain	Biological: Fluzone® (Aventis Pasteur inactivated influenza vaccine); A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002

Outcome Measures

Primary Outcome Measures

1. Immune Response: Age 18-49 [21 days post-vaccincation]

   Immune response as measured by viral strain specific hemaggluttination inhibition (HAI) antibody levels for subjects ages 18-49

2. Immune Response: Age 50-64 [21 days post-vaccincation]

   Immune response as measured by viral strain specific hemaggluttination inhibition (HAI) antibody levels for subjects ages 50-64

Secondary Outcome Measures

1. Medical Events: Unsolicited Adverse Events [3 - 6 months following vaccination]

   Assessed through following subjects' recording of oral body temperature, completion of a 21-day symptom diary; subjects' completion of longer-term follow-up surveys to track respiratory symptoms; and a review of the Defense Medical Surveillance System (DMSS) hospitalization and outpatient medical visits database in order to track ICD-9 codes relevant to flu-like illness.

Other Outcome Measures

1. Race/Ethnicity Baseline Measure [Enrollment Day]

   Race/ethnicity data was only collected by age and cannot be separated out by dose as per the other Baseline Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Able to understand and comply with all study procedures including availability for all study visits and follow up surveys within 6 months following study enrollment.

• DEERS eligible beneficiaries eligible for influenza vaccination and able to give informed consent.

• Age 18-49

• Patients presenting to travel clinic with no exclusion criteria;

• Household contacts and out-of-home caretakers of infants from 6-23 months of age;

• Hospital and/or employees providing service to the public who are not eligible for the post-October 5th recommendations for priority immunization;

• DOD employees eligible for influenza vaccination prior to October 5th but excluded in the post October 5th guidelines;

• People living in dormitories or under other crowded conditions, to prevent outbreaks;

• Ages 50-64 years of age who are not eligible for the post-October 5th recommendations for priority immunization and with no standard of care contraindications to vaccination.

• Eligible in the Department of Defense for influenza vaccination

Exclusion Criteria:

• all children aged < 18 years (includes children aged 6 months-18 years on chronic aspirin therapy);

• adults aged >65 years;

• persons aged 2-64 years with underlying chronic medical conditions:

• includes persons with chronic cardiac or pulmonary disease, diabetes mellitus, hemoglobinopathy, or immunosuppressive illness;

• any acute or chronic condition that, in the opinion of the investigator, would render vaccination unsafe or interfere with the evaluation of response.

• use of experimental vaccines or medications within 30 days of study entry;

• receipt of parenteral immunoglobulin within 60 days of study entry;

• all women who will be pregnant during the influenza season;

• residents of nursing homes and long-term care facilities;

• health-care workers involved in direct patient care and included in DOD priority 1; and;

• military recruits;

• out-of-home caregivers and household contacts of children aged <6 months.

• Anyone with clinical contraindications for receiving the inactivated influenza vaccine such as a history of severe allergic reaction to prior influenza vaccinations, severe allergy to egg and/or egg proteins and gelatin.

• DOD Priority 1: Deployed or deploying (with orders) service members and others designated as critical to national defense.

• DOD Priority 2: Medically high risk in accordance with ACIP guidelines (includes health-care workers with direct patient contact)

• Any acute or chronic condition that, in the opinion of the investigator or her provider designee would render vaccination unsafe or interfere with the evaluation of the response.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pentagon	Washington	District of Columbia	United States	20050
2	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307

Sponsors and Collaborators

• U.S. Army Medical Research and Development Command
• Walter Reed Army Medical Center
• United States Army Medical Materiel Development Activity
• Centers for Disease Control and Prevention
• Uniformed Services University of the Health Sciences
• Walter Reed Army Institute of Research (WRAIR)
• U.S. Air Force Office of the Surgeon General

Investigators

• Principal Investigator: Renata J Engler, M.D, Walter Reed Army Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT00283283
• Other Study ID Numbers: A-13205
• First Posted: Jan 27, 2006
• Last Update Posted: Feb 12, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by U.S. Army Medical Research and Development Command: Influenza
• Additional relevant MeSH terms: Influenza, Human

Study Results

Participant Flow

Recruitment Details	Study participants were recruited at the Walter Reed Army Medical Center Allergy-Immunization Clinic, the Fort Belvoir DeWitt Allergy-Immunization Clinic and the Pentagon Health Clinic during the annual influenza immunization program.
Pre-assignment Detail	Enrollment was expanded to include subs with a history of flu vacs. From the originally enrolled subjects (1316), the final data analysis includes only members of the baseline re-vaccination population (1114).

Arm/Group Title	Full Dose, Age 18-49	Half Dose, Age 18-49	Full Dose, Age 50-64	Half Dose, Age 50-64
Arm/Group Description	Subjects age 18-49 receiving full dose	Subjects age 18-49 receiving half dose	Subjects age 50-64 receiving full dose	Subjects age 50-64 receiving half dose
Period Title: Overall Study
STARTED	274	284	280	276
COMPLETED	274	284	280	276
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Full Dose, Age 18-49	Half Dose, Age 18-49	Full Dose, Age 50-64	Half Dose, Age 50-64	Total
Arm/Group Description	Previously Vaccinated Subjects Receiving Full Dose Aged 18-49 Years	Previously Vaccinated Subjects Receiving Half Dose Aged 18-49 Years	Previously Vaccinated Subjects Receiving Full Dose Aged 50-64 Years	Previously Vaccinated Subjects Receiving Half Dose Aged 50-64 Years	Total of all reporting groups
Overall Participants	274	284	280	276	1114
Age, Customized (years) [Number]
Number [years]	274	284	280	276	1114
Sex: Female, Male (Count of Participants)
Female	126 46%	121 42.6%	119 42.5%	118 42.8%	484 43.4%
Male	148 54%	163 57.4%	161 57.5%	158 57.2%	630 56.6%
Region of Enrollment (participants) [Number]
United States	274 100%	284 100%	280 100%	276 100%	1114 100%

Outcome Measures

1. Primary Outcome

Title	Immune Response: Age 18-49
Description	Immune response as measured by viral strain specific hemaggluttination inhibition (HAI) antibody levels for subjects ages 18-49
Time Frame	21 days post-vaccincation

Outcome Measure Data

Analysis Population Description

From the 1263 subjects enrolled, final analysis includes baseline re-vaccinated subs who fit all inc/exc criteria and whose serum specimens were usable. Data summarizes the differences in influenza strain specific serologic responses according to vaccine dose and age. Antibodies were measured by Hemagglutination Inhibition. GMT=Geometric Mean Titer

Arm/Group Title	Age 18 - 49, Full Dose	Age 18 - 49, Half Dose
Arm/Group Description	0.5ml, 15µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain Fluzone® (Aventis Pasteur inactivated influenza vaccine): A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002	0.25ml, 7.5µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinia per strain Fluzone® (Aventis Pasteur inactivated influenza vaccine): A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Measure Participants	274	284
H1N1 - GMT	28.8	21.3
H3N2 - GMT	55.2	45.0
B - GMT	69.6	54.8

2. Primary Outcome

Title	Immune Response: Age 50-64
Description	Immune response as measured by viral strain specific hemaggluttination inhibition (HAI) antibody levels for subjects ages 50-64
Time Frame	21 days post-vaccincation

Outcome Measure Data

Analysis Population Description

From the 1263 subjects enrolled, final analysis includes baseline re-vaccinated subs who fit all inc/exc criteria and whose serum specimens were usable. Data summarizes the differences in influenza strain specific serologic responses according to vaccine dose and age. Antibodies were measured by Hemagglutination Inhibition. GMT=Geometric Mean Titer

Arm/Group Title	Age 50 - 64, Full Dose	Age 50 - 64, Half Dose
Arm/Group Description	0.5ml, 15µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain Fluzone® (Aventis Pasteur inactivated influenza vaccine): A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002	0.25ml, 7.5µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinia per strain Fluzone® (Aventis Pasteur inactivated influenza vaccine): A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
Measure Participants	280	276
H1N1 - GMT	21.4	14.2
H3N2 - GMT	59.0	39.1
B - GMT	52.1	36.8

3. Secondary Outcome

Title	Medical Events: Unsolicited Adverse Events
Description	Assessed through following subjects' recording of oral body temperature, completion of a 21-day symptom diary; subjects' completion of longer-term follow-up surveys to track respiratory symptoms; and a review of the Defense Medical Surveillance System (DMSS) hospitalization and outpatient medical visits database in order to track ICD-9 codes relevant to flu-like illness.
Time Frame	3 - 6 months following vaccination

Outcome Measure Data

Analysis Population Description

Of the original population, 1203 previously vaccinated subjects completed the 3-day post vaccination side effects diary and have been included in the this analysis.

Arm/Group Title	Mild	Moderate	Severe, Able to Work	Severe, Lost Productivity	No Events
Arm/Group Description	Mild AE	Moderate AE	Severe but able to work	Severe and lost productivity	No adverse events recorded
Measure Participants	1203	1203	1203	1203	1203
Body as a Whole	0	6	1	3	1193
Cardiovascular System	2	2	0	0	1199
Digestive Sytem	12	3	2	4	1182
Hematological and Lymphatic System	2	0	1	0	1200
Musculoskeletal System	6	5	1	1	1190
Respiratory System	10	18	5	3	1167
Skin and Appendages	14	8	1	0	1180
Special Senses	2	2	0	1	1198
Urogenital System	0	4	0	0	1199
Symptions in Arm Given Shot	13	1	0	0	1189
Headache	0	2	1	1	1199

4. Other Pre-specified Outcome

Title	Race/Ethnicity Baseline Measure
Description	Race/ethnicity data was only collected by age and cannot be separated out by dose as per the other Baseline Measures
Time Frame	Enrollment Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aged 18-49 y (n=558)	Aged 50-64 y (n=556)
Arm/Group Description	Race/Ethnicity stratified by age 18-49	Race/Ethnicity stratified by age 50-64
Measure Participants	558	556
White	454 165.7%	491 172.9%
African American	54 19.7%	46 16.2%
Hispanic	16 5.8%	6 2.1%
Asian	14 5.1%	7 2.5%
Other/unknown	10 3.6%	6 2.1%

Adverse Events

Time Frame	3 - 6 months following vaccination
Adverse Event Reporting Description	Of the original study population, 1203 previously vaccinated subjects completed the 3-day post vaccination side effects diary and have been included in this analysis. AEs were collected with diary cards, health surveys, and VAERS forms and listed by subject Grading of AE's: 1 = Mild; 2 = Moderate; 3 = Severe, able to work; 4 = Severe, lost productivity; 5 = Life-threatening; 6 = Fatal
Arm/Group Title	Full Dose		Half Dose
Arm/Group Description	0.5ml, 15µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinin antigen per strain Fluzone® (Aventis Pasteur inactivated influenza vaccine): A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002		0.25ml, 7.5µg Fluzone® (Aventis Pasteur inactivated influenza vaccine) hemagglutinia per strain Fluzone® (Aventis Pasteur inactivated influenza vaccine): A/H1N1, A/New Caledonia/20/99; A/H3N2, A/Fujian/411/2002; B, B/Shanghai/361/2002
All Cause Mortality
	Full Dose		Half Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/554 (0%)		0/556 (0%)
Serious Adverse Events
	Full Dose		Half Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/554 (0.4%)		1/556 (0.2%)
Cardiac disorders
Carotid endarterectomey	0/554 (0%)	0	1/556 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/554 (0.2%)	1	0/556 (0%)	0
Surgical and medical procedures
Melanoma exised	1/554 (0.2%)	1	0/556 (0%)	0
Other (Not Including Serious) Adverse Events
	Full Dose		Half Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/554 (3.2%)		17/556 (3.1%)
Blood and lymphatic system disorders
Swollen lymph nodes	0/554 (0%)	0	1/556 (0.2%)	1
Swollen lymph nodes in neck, sore throat, chills, body aches	0/554 (0%)	0	1/556 (0.2%)	1
Gastrointestinal disorders
Diarrhea	2/554 (0.4%)	2	0/556 (0%)	0
Irritable bowel syndrome	1/554 (0.2%)	1	0/556 (0%)	0
Nausea	0/554 (0%)	0	1/556 (0.2%)	1
Nausea and body aches	0/554 (0%)	0	1/556 (0.2%)	1
General disorders
Fever, chills, flu-like symptoms	1/554 (0.2%)	1	0/556 (0%)	0
Flu-like symptoms	0/554 (0%)	0	1/556 (0.2%)	1
Flu-like symptoms	0/554 (0%)	0	1/556 (0.2%)	1
Immune system disorders
Idiopathic urticaria	0/554 (0%)	0	1/556 (0.2%)	1
Infections and infestations
Outbreak of HSV on face, also nasal lesions	1/554 (0.2%)	1	0/556 (0%)	0
Injury, poisoning and procedural complications
Brusing at injection site	4/554 (0.7%)	4	1/556 (0.2%)	1
Bruising at injection site	0/554 (0%)	0	1/556 (0.2%)	1
Aching at injection site	1/554 (0.2%)	1	0/556 (0%)	0
Arm sore at injection site	1/554 (0.2%)	1	0/556 (0%)	0
Hurt at injection site	0/554 (0%)	0	1/556 (0.2%)	1
Ichiness at injection site	0/554 (0%)	0	1/556 (0.2%)	1
Injection site soreness	3/554 (0.5%)	3	2/556 (0.4%)	2
Itching, distil to injection site	1/554 (0.2%)	1	1/556 (0.2%)	1
Pain in right antecubital area after venipuncture	1/554 (0.2%)	1	0/556 (0%)	0
Tender at injection site	1/554 (0.2%)	1	0/556 (0%)	0
Tingling in fingers of vaccinated arm	1/554 (0.2%)	1	0/556 (0%)	0
Very sore at injection site	0/554 (0%)	0	1/556 (0.2%)	1
Musculoskeletal and connective tissue disorders
Body aches	0/554 (0%)	0	1/556 (0.2%)	1
Right shoulder pain	1/554 (0.2%)	1	0/556 (0%)	0
Sore, achy shoulder	0/554 (0%)	0	1/556 (0.2%)	1
Skin and subcutaneous tissue disorders
Rash on right calf	1/554 (0.2%)	1	0/556 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.