Clinical Immunization Safety Assessment (CISA) Project Current Studies

CISA studies use the most current methods and technology to investigate questions of key importance to vaccine safety.

2014

• Utilizing Outcomes-based, Case-Centered Analytic Methods for Assessments of the Causality of Adverse Events Following Immunization
  Scientists use various epidemiological and statistical methods to study possible links between vaccines and the occurrence of adverse events after vaccination. One such method is the case-centered analytic method, in which scientists search for a rare or unusual medical diagnosis of interest among all diagnoses in a large patient database that includes thousands or even millions of vaccine administration records. Scientists use statistical methods to look at the potential relationships, such as patterns in time, between administration of any vaccines and the diagnosis of interest. CISA will apply case-centered statistical analytic methods to assess whether specific adverse outcomes might be associated with an increased likelihood of receipt of one of more vaccines.  The results of the analysis will supplement other information we review for CISA clinical case consultations: medical records, scientific literature, manufacturer package inserts, similar adverse event reports from the Vaccine Adverse Event Reporting System (VAERS), and expert opinion. We plan to assess the feasibility and usefulness of applying case-centered analyses to vaccine adverse event causality assessments.
  Lead CISA Site: Kaiser Permanente Northern California
  Collaborator: CDC
• Oral Water Hydration to Prevent Post-Vaccination Presyncope Study
  Receiving a vaccine can cause syncope (fainting), usually within 15 minutes of vaccination(s). Syncope is uncommon after vaccination, but may lead to injuries when it occurs. Some people experience symptoms of “presyncope”, including feeling lightheaded, after vaccination; some people who have pre-syncope will then lose consciousness.  The American Academy of Pediatrics (AAP) recommends that all adolescents be sitting or lying down, and observed for at least 15 minutes after vaccination to prevent potential injuries related to fainting after vaccination.  Drinking 500 ml of water within fifteen minutes before blood is drawn has been shown to help prevent syncope and presyncope among blood donors.  It is not known if drinking water would also prevent presyncope and syncope after vaccination.  We plan to conduct a randomized study in adolescents and young adults (aged 11-21 years) receiving at least one intramuscular (IM) vaccine to evaluate the acceptability and impact of oral hydration to prevent presyncope following vaccination. The primary goals of this study are: 1) To determine if drinking water before vaccination  decreases the rate of presyncope in adolescents and young adults receiving at least one IM vaccine; and 2) To determine if  drinking water before vaccination is acceptable to adolescents and young adults. Our secondary objectives are: 1) To describe the rates of presyncope (and syncope) in adolescents and young adults receiving at least one IM vaccine; and 2) To evaluate the association between characteristics, such as age of the person vaccinated and  type of vaccine(s) received, and presyncope signs and symptoms.  Information from this study has the potential to help us prevent presyncope and syncope after vaccination.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT02353390).
  Lead CISA Site: Duke University
  Contributing CISA Site: Boston Medical Center
  Collaborator: CDC
• Fever and Wheezing Events in Children After US Influenza Vaccines Using Text Messaging Study
  Text messaging is a useful way to monitor persons for vaccine adverse events because it is inexpensive and can gather information rapidly from many people at the same time. It also allows for monitoring of health issues that often don’t lead to medical visits, such as fever or wheezing. The person vaccinated or their caregiver reports symptoms using text messaging. In this study, we are assessing the feasibility of using text messaging to assess fever rates and asthma/wheezing rates in healthy children aged 2 through 11 years on vaccination day and during the next 42 days (days 0-42) after administration of influenza vaccines. Demonstrating the feasibility of using text messaging to assess wheezing episodes could provide important new information since previous studies using text message monitoring after vaccination have been for fever only. Also to date, in the United States, text messaging has only been used to assess vaccine safety at Columbia University in New York. Expanding use of text messaging to monitor adverse events in another part of the country can provide additional information. This study could provide information that would help plan for vaccine safety monitoring during an influenza pandemic or other emergency vaccination program.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT02295007).
  Lead CISA Site: Columbia University
  Contributing CISA Site: Boston Medical Center
  Collaborator: CDC
• The Effect of Prophylactic Antipyretics on Immune Responses and Fever After 2014-2015 Inactivated Influenza Vaccine Study
  Using prophylactic (preventive) antipyretics (fever reducers) immediately after vaccination and during the next 24 hours reduces the rate of fever following vaccination. However, giving these medicines, such as acetaminophen or ibuprofen, to prevent fever after vaccination may also blunt immune responses to the vaccine. CISA is conducting a study to assess the effect of prophylactic antipyretics on the immune responses and rates of fever after inactivated influenza vaccine (IIV) in healthy children 6 through 47 months of age, during the 2014-15 influenza season. This study builds on lessons learned from a CISA pilot study on antipyretics and influenza vaccine, conducted during the 2013-14 influenza season (see below). Children are randomized to receive prophylactic acetaminophen or oral placebo without the patient/parent or provider knowing which they are receiving (blinded) or open-label (not blinded) ibuprofen for 24 hours starting immediately after receipt 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 day following vaccination. Antibody to influenza antigens contained in the 2014-2015 vaccine will also be assessed at baseline and four weeks following vaccination. Information from this study will be used to better understand potential risks and benefits of using prophylactic antipyretics to prevent fever or febrile seizure after IIV and design future studies.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT02212990).
  Lead CISA Site: Duke University
  Collaborator: CDC

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2013

• Pilot Study to Assess the Effect of Prophylactic Antipyretics on Immune Responses and Fever After IIV
  Using prophylactic (preventive) antipyretics, such as acetaminophen,immediately after the vaccination and during the next 24 hours reduces the rate of fever after vaccination. However, giving antipyretics to prevent fever after vaccination may also blunt immune responses to the vaccine. CISA conducted a double-blind, pilot study to assess the effect of prophylactic antipyretics on the immune responses and rates of fever after inactivated influenza vaccine (IIV) in healthy children 12 through 35 months of age. Children were randomized to receive prophylactic acetaminophen or oral placebo for 24 hours starting immediately after receipt of IIV. Information from this pilot study was used to design a larger study (above) to better understand potential risks and benefits of using prophylactic antipyretics to prevent fever or febrile seizure after IIV.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT01946594).
  Lead CISA Site: Duke University
  Collaborator: CDC
• PregText: Feasibility of Monitoring Influenza Vaccine Safety in Pregnant Women Using Text Messaging
  Text messaging may be a convenient and cost-efficient way to monitor vaccine safety in pregnant women, but it has not been studied. CISA is conducting a study to assess the feasibility of using text messaging to monitor the safety of inactivated influenza vaccine (IIV) in pregnant women. Pregnant women <20 weeks gestation receiving IIV as part of usual care are included. These women receive periodic text messages after IIV throughout their pregnancy to 1) monitor rates of fever shortly after IIV and 2) assess pregnancy outcomes. Results of this study may help enhance future vaccine safety monitoring efforts in pregnant women and preparedness for an influenza pandemic.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT01974050).
  Lead CISA Site: Columbia University
  Collaborator: CDC
• Immune and Hormone Response to Influenza Vaccine
  Influenza vaccine is routinely recommended for people 6 months of age and older, including women of reproductive age. Giving inactivated influenza vaccine (IIV) induces an early immune or germ-fighting response and changes the body’s level of cytokines. Cytokines are substances that are secreted by immune cells and act on other cells to coordinate appropriate immune responses. It is not known whether this cytokine response might affect female reproductive hormone levels. CISA is conducting a pilot study to assess whether women’s reproductive hormone levels change during the menstrual cycle after receiving IIV. Healthy women 18-39 years of age are participating during 2 menstrual cycles. In one cycle the women receive IIV during the week before ovulation, and in the other cycle (control cycle) they do not receive any vaccines. The level of reproductive hormones and cytokines are being measured during these menstrual cycles at several time points. This study is assessing the feasibility of conducting further research in this area in order to better understand the effects of vaccination on women’s reproductive hormones.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT01978262).
  Lead CISA Site: Johns Hopkins University
  Collaborator: CDC
• Clinical Study of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine (Tdap) Safety in Pregnant Women
  Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) is routinely recommended during each pregnancy (MMWR, February 22, 2013 / 62(07); 131-135). When a woman receives Tdap during pregnancy she makes antibodies against pertussis (whooping cough) that are transferred to the baby across the placenta. These antibodies provide some protection to infants from pertussis until they are old enough to be vaccinated themselves. CISA is conducting a multisite study to evaluate health outcomes in women who receive Tdap during pregnancy. Pregnant women ≥20 weeks gestational age and non-pregnant women receiving Tdap vaccine as part of routine care are participating. The study is comparing rates of injection site and systemic reactions, such as fever, after Tdap in pregnant women versus non-pregnant women. It is also assessing rates of preterm birth and small for gestational age (SGA) in women who receive Tdap during pregnancy, compared with background rates of these conditions. Pregnant women enrolled in the study are participating through delivery. Their infants are also being evaluated for health outcomes and growth parameters through age 6 months. Non-pregnant women are participating for one month after vaccination. This study will provide additional information about the safety of using Tdap in pregnant women, including repeated Tdap doses.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT02209623.)
  Lead CISA Site: Vanderbilt University
  Contributing CISA Site: Duke University
  Collaborator: CDC, National Vaccine Program Office
• Enhancing an Online Tool for Assessing the Causality of Adverse Events Following Immunization
  The U.S. National Vaccine Plan has an objective to improve causality assessments of vaccines and associated adverse events following immunization (AEFI). CISA created an algorithm and an online test tool to guide healthcare providers through the steps necessary to evaluate whether a vaccine might have been associated in a causal way with the development of an AEFI in an individual patient. The purpose of this project is to enhance the online causality test tool for AEFI and determine how useful it might be to clinicians and public health professionals, outside the CISA Project.
  Lead CISA Site: Johns Hopkins University
  Collaborator: CDC

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2012

• Assessing Fever Rates in Children ages 24 to 59 months after Live Attenuated Influenza Vaccine(LAIV) or Inactivated Influenza Vaccines (IIV) Using Text Messaging for U.S. influenza vaccines in 2012–13 & 2013-2014
  Some children have fevers after receiving vaccines, including influenza vaccines.  In recent years there have been 4 main kinds of influenza vaccines for children: trivalent inactivated influenza vaccine (IIV3) (3 strain, flu shot), trivalent live attenuated influenza vaccine (LAIV3) (3 strain, nasal spray), IIV4 (4 strain, flu shot) and LAIV4 (4 strain, nasal spray). CISA is conducting a study that is assessing the rates of fever in healthy children 24-59 months of age after they receive pediatric influenza vaccines. The child’s temperature is taken on vaccination day (day 0) and for the next 10 days. These temperature readings are sent to study staff using text messaging each day. The main objective is to compare rates of fever after LAIV vs IIV in the 0-2 days after vaccination, when rates of fever are expected to be highest. Information from this study will help healthcare providers and parents better understand the risk for fever in young children after different kinds of influenza vaccines.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT01764269).
  Lead CISA Site: Columbia University
  Collaborator: CDC
• Pilot Study to Assess Flares of Illness Following Receipt of Inactivated Influenza Vaccine in Youth with Systemic Lupus Erythematosus (SLE)
  Vaccines stimulate the immune system to develop protection against diseases. The effect of vaccination on disease progression among people with autoimmune diseases who are immunosuppressed is not well studied. CISA is conducting a pilot study of inactivated influenza vaccine (IIV) safety in children/adolescents with systemic lupus erythematosus (SLE) who are immunosuppressed, in order to inform methods for a larger study assessing association of IIV and SLE flares.
  More information about this study can be found at ClinicalTrials.gov (Identifier: NCT02006784).
  Lead CISA Site: Vanderbilt University, with subcontract to the Baylor Institute for Immunology Research (BIIR)
  Collaborator: CDC

Projects/Studies initiated under the CISA Network (2001-2012)

The CISA Network has published numerous studies and technical reports on vaccine safety.

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