Safety and Immunogenicity Study of Influenza Vaccines in HIV-infected and HIV-uninfected Pregnant Women in Western Kenya
This study is not yet open for participant recruitment.
Verified March 2013 by Centers for Disease Control and Prevention
Sponsor:
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01810731
First received: March 12, 2013
Last updated: March 15, 2013
Last verified: March 2013
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Purpose
In 2012, the WHO Strategic Advisory Group of Experts (SAGE) concluded that pregnant women are the most important risk group for season influenza vaccination based upon "compelling evidence of substantial risk of severe disease in this group and evidence that seasonal influenza vaccine is safe and effective in preventing disease in pregnant women as well as their young infants, in whom disease burden is also high". Recent data from Kenya, similarly suggest rates of influenza-associated hospitalizations in children under age 1 to be as high, or higher, than those observed in the United States. However, TIV may have reduced immunogenicity in HIV-infected adults, and HIV infection has been shown to reduce placental transfer of both tetanus and measles antibodies. Adjuvanted influenza vaccine has been shown to induce higher antibody titers in children and older adults. Therefore, we propose to conduct a double-blind randomized controlled trial of influenza vaccines stratified by HIV status in up to 720 pregnant women in their second and third trimesters and their infants residing in health and demographic surveillance sites (HDSS) in Nyanza Province, Western Kenya. We propose to assess the safety, immunogenicity, and efficacy of traditional TIV and an adjuvanted TIV product in HIV-infected and HIV-uninfected pregnant women. Findings will inform maternal influenza vaccination policies in Kenya and other African countries.
| Condition | Intervention | Phase |
|---|---|---|
|
Influenza, Human HIV Malaria Tetanus Polio |
Biological: Trivalent Inactivated Influenza Vaccine Biological: Adjuvanted Trivalent Inactivated Influenza Vaccine Biological: Inactivated Polio Vaccine |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention |
| Official Title: | A Double-Blind, Randomized, Controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of Trivalent Inactivated Influenza Vaccine and Adjuvanted Trivalent Inactivated Influenza Vaccine in HIV-Infected and HIV-Uninfected Pregnant Women in a Malaria-Endemic Area of Rural Western Kenya |
Resource links provided by NLM:
Further study details as provided by Centers for Disease Control and Prevention:
Primary Outcome Measures:
- Proportion of women with an appropriate rise in Hemagglutination Inhibition (HI) titers [ Time Frame: Enrollment (Day 0) vs. Day 28 for each study arm ] [ Designated as safety issue: No ]The proportion of TIV and aTIV recipients with a fourfold rise in HI titers or HI titers ≥40 if baseline HI titer <10 compared to the same proportion in controls
- Proportion of infants born to TIV and aTIV recipients with HI titers greater than or equal to 40 in cord blood compared to same in controls. [ Time Frame: At delivery ] [ Designated as safety issue: No ]
- Number of solicited and unsolicited adverse events post-vaccination by study arm [ Time Frame: During follow-up period, approx. 9 months ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Vaccine efficacy of TIV and aTIV in mothers and infants compared to control mothers and infants. [ Time Frame: Entire follow-up period, approx. 9 months ] [ Designated as safety issue: No ]Incidence of influenza infection will be measured in all participants by surveillance for influenza-like illness (ILI) throughout the study period. Women with fever and cough will be tested for influenza via rRT-PCR of NP/OP swabs. Infants with fever, hypothermia, or any respiratory symptom will also be tested for influenza via rRT-PCR of NP/OP swabs.
- HIV infection and placental antibody transfer [ Time Frame: Delivery ] [ Designated as safety issue: No ]Compare geometric mean HI titers and geometric mean tetanus antibody titers at delivery in HIV-infected and HIV-uninfected mothers with titers in cord blood.
- Birth weight [ Time Frame: Delivery ] [ Designated as safety issue: No ]Compare birth weight adjusted for gestational age among TIV and a TIV recipients compared to controls.
- Peripheral and placental parasitemia impact on vaccination [ Time Frame: Day 0 and delivery ] [ Designated as safety issue: No ]Compare change in geometric mean HI titers from day 0 to day 28 in women with and without peripheral parasitemia at the time of vaccination. Compare amount of passive antibody transfer to infants in cord blood in mothers with and without placental parasitemia
- baseline polio immunity and polio antibody transfer [ Time Frame: day 0 and delivery ] [ Designated as safety issue: No ]Assess baseline immunity to polio types 1, 2, 3 among all study participants. Assess polio antibody transfer to infants from mothers who did and did not receive IPV.
| Estimated Enrollment: | 720 |
| Study Start Date: | August 2013 |
| Estimated Study Completion Date: | April 2016 |
| Estimated Primary Completion Date: | December 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Trivalent Influenza Vaccine (TIV)
15µg of each of 2 influenza A strains (H1N1 and H3N2) and 1 influenza B strain in a buffer solution totaling 0.5mL which is administered intramuscularly. Administered as a single dose on the day of enrollment. |
Biological: Trivalent Inactivated Influenza Vaccine
Other Names:
|
|
Experimental: Adjuvanted TIV (aTIV)
15 µg of each of 2 influenza A strains and 1 influenza B strain with a proprietary adjuvant, M59™, in a volume of 0.5mL administered intramuscularly. M59 is an oil-in-water emulsion composed of squalene, polysorbate 80, and sorbitan trioleate in a citrate buffer. Administered as a single dose on the day of enrollment. |
Biological: Adjuvanted Trivalent Inactivated Influenza Vaccine
Other Name: Fluad, Novartis Vaccines and Diagnostics, Inc.
|
|
Active Comparator: Inactivated Polio Vaccine
A sterile suspension of three types of poliovirus: Type 1 (Mahoney), Type 2 (MEF1) and Type 3 (Saukett). This vaccine is prepared from types 1, 2 and 3 of poliomyelitis virus cultured on Vero cells, purified and then inactivated by formaldehyde and administered as a 0.5ml intramuscular or subcutaneous injection. A single dose of vaccine will be administered upon enrollment.
|
Biological: Inactivated Polio Vaccine
Other Name: Imovax, Sanofi Pasteur SA
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 13 Years to 49 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Resident of HDSS village
- Singleton pregnancy
- Second or third trimester (after quickening) but before 33 weeks of gestation by fundal height
- Does not plan to relocate out of the HDSS area or population-based surveillance site in the next 12 months and agrees to all follow-up visits/contact by phone
- Is not currently enrolled in another intervention study
- Provides informed consent by signature or thumb print
- Consents to HIV testing and counseling as required
- Willing to deliver in the labor ward of the study hospital
- No history of chronic illness requiring multiple hospitalizations or prolonged medical therapy (except HIV on ART)
Exclusion Criteria:
- History of allergic reaction to any component of the study vaccines
- Residence outside the study area or planning to relocate out in the 9 months following enrollment
- Received immunoglobulin or blood products within 45 days of study entry
- Used immunosuppressive medication within 45 days of study entry (inhaled and topical corticosteroids permitted)
- High risk pregnancy including any pre-existing condition likely to cause complications of pregnancy (hypertension, diabetes, current asthma, eclampsia or pre-eclampsia, epilepsy, heart disease, renal disease, liver disease, fistula repair, leg or spine deformity)
- Unable to give informed consent (for example due to mental disability)
- Previous enrollment in a study with similar interventions
- Gestational age >32 weeks by last menstrual period or fundal height
- Acutely ill with temperature ≥37.5°C on the day of randomization/vaccination
- Hemoglobin <7.0 g/dL
- Influenza vaccination in previous 12 months
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01810731
Contacts
| Contact: Meredith L McMorrow, MD, MPH | 404-639-4973 | bwe3@cdc.gov |
Locations
| Kenya | |
| Siaya District Hospital | Not yet recruiting |
| Siaya, Kenya | |
Sponsors and Collaborators
Investigators
| Study Director: | Meredith L McMorrow, MD, MPH | Centers for Disease Control and Prevention |
| Principal Investigator: | Joshua A Mott, PhD | Centers for Disease Control and Prevention Kenya Country Office |
| Principal Investigator: | Nancy Otieno, MS | Kenya Medical Research Institute |
| Study Director: | Marc-Alain Widdowson, VetMB, MSc | Centers for Disease Control and Prevention |
More Information
No publications provided
| Responsible Party: | Centers for Disease Control and Prevention |
| ClinicalTrials.gov Identifier: | NCT01810731 History of Changes |
| Other Study ID Numbers: | CDC-NCIRD-6393 |
| Study First Received: | March 12, 2013 |
| Last Updated: | March 15, 2013 |
| Health Authority: | United States: Federal Government Kenya: Ethical Review Committee Kenya: Institutional Review Board Kenya: Pharmacy and Poisons Board United States: Data and Safety Monitoring Board United States: Institutional Review Board |
Keywords provided by Centers for Disease Control and Prevention:
|
influenza vaccine immunogenicity HIV pregnancy influenza vaccine safety adjuvanted influenza vaccine |
Additional relevant MeSH terms:
|
Influenza, Human Malaria Poliomyelitis Tetanus Orthomyxoviridae Infections RNA Virus Infections Virus Diseases Respiratory Tract Infections Respiratory Tract Diseases Protozoan Infections Parasitic Diseases Myelitis |
Central Nervous System Viral Diseases Enterovirus Infections Picornaviridae Infections Central Nervous System Infections Central Nervous System Diseases Nervous System Diseases Spinal Cord Diseases Neuromuscular Diseases Clostridium Infections Gram-Positive Bacterial Infections Bacterial Infections |
ClinicalTrials.gov processed this record on May 16, 2013