Clinical trial NCT05283902: Effectiveness, Immunogenicity and Safety of the Second Booster Dose of the Vaccine Against COVID-19 in the Elderly
Official title: Effectiveness, Immunogenicity and Safety of the Second Booster Dose (Fourth Dose) of the Vaccine Against COVID-19 in the Elderly: Study Reforça Mais (Plus Booster)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: COVID-19
Vaccine Adverse Reaction
Vaccine-Preventable Diseases
Lead sponsor: Federal University of Espirito Santo
Sponsor class: OTHER
Collaborators: name: Secretaria de Estado da Saúde do Espírito Santo - SESA
name: Centro de Pesquisas René Rachou
First posted: 2022-03-17
Enrollment: 490000
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and forty participants, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection for the immunogenicity study, in a health unit in Cariacica-ES. This sub-sample will be compared with 240 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers.

Brief summary: The objective of this observational case-crossover study is to evaluate the effectiveness, safety and immunogenicity of the second booster dose in the elderly. There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and forty participants will be invited to participate in biological sample for the immunogenicity study. This sub-sample will be compared with 240 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers. The main effectiveness outcome will be the number of hospitalizations; and secondary outcomes will be deaths, number of reported cases, number of cases confirmed by RT-PCR. The safety assessment will be carried out by monitoring adverse events. The cellular and humoral immune response will be evaluated by viral neutralization assay (search for neutralizing antibodies), serological assay by chemiluminescence, determination of specific IgM and IgG profile, dosage of soluble systemic factors (chemokines, cytokines and growth factors), stimulation in vitro antigen-specific peripheral blood mononuclear cells and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. The study hypothesis is that elderly people who received the second booster dose have a lower incidence rate of hospitalizations and death than those who received the primary regimen (two doses or one of Janssen) or a booster dose, and that the immune response humoral and cellular function of the elderly is similar to those who are immunosuppressed.

Detailed description: Faced with the new scenario of high transmission of the Ômicron variant of SARS-COV-2, in which the elderly over 60 years and immunosuppressed even vaccinated with three doses have become a population vulnerable to a greater probability of serious illness by Covid-19, demanding an increase in risk of hospitalization and deaths, the application of the fourth dose (second booster dose) has become an alternative to increase protection for these individuals. The general objective of this study is to evaluate the effectiveness, safety and immunogenicity of the second booster dose in the elderly. This is an observational, case-crossover study, based on databases with notification and vaccination records and a cohort study for the analysis of immunogenicity. Elderly people of both sexes aged 60 years or older, residents of Espírito Santo, will be included. There are an estimated 490,000 eligible individuals aged 60 and over statewide for the effectiveness study. Two hundred and forty participants, with quotas distributed by sex (50% male and 50% female) and age group, will be invited to participate in biological sample collection on the day of application of the second booster dose (T1) , 28 days after the second booster dose (T2), at the follow-up visit after 3 months (T3), 150 days (T4) and 180 days (T5), for follow-up of vaccine response and follow-up of duration of immunity, in a health unit in Cariacica-ES. This sub-sample will be compared with 240 biorepository samples from a cohort of immunosuppressed patients with autoimmune diseases who received the fourth dose, in a study conducted by the same team of researchers. The main effectiveness outcome will be the number of hospitalizations, weighted by protection time, 90 days after complete immunization (14th day after second booster dose); and secondary outcomes will be deaths, number of reported cases, number of cases confirmed by RT-PCR. The safety assessment will be carried out by monitoring adverse events. The cellular and humoral immune response will be evaluated by viral neutralization assay (search for neutralizing antibodies), serological assay by chemiluminescence, determination of specific IgM and IgG profile, dosage of soluble systemic factors (chemokines, cytokines and growth factors), stimulation in vitro antigen-specific peripheral blood mononuclear cells and investigation of memory T and B lymphocytes and intracytoplasmic cytokines. The study hypothesis is that elderly people who received the second booster dose have a lower incidence rate of hospitalizations and death than those who received the primary regimen (two doses or one of Janssen) or a booster dose, and that the immune response humoral and cellular function of the elderly is similar to those who are immunosuppressed.

Eligibility criteria: Inclusion Criteria:

* Age equal to or greater than 60 years
* Residents of Espírito Santo, Brazil

Exclusion Criteria:

* Being under active treatment (chemotherapy and/or radiotherapy) for the treatment of any type of neoplasm
* Being admitted to an institutionalization establishment for the elderly (hospitals, nursing homes, shelters or similar).
* Patients with mental illness with inability to understand the consent form

Primary outcomes:
measure: number of hospital admissions
timeFrame: Change from baseline at 6 months
measure: Number of adverse events
timeFrame: Change from baseline at 1 month
Secondary outcomes:
measure: number of deaths
timeFrame: Change from baseline at 6 months
measure: number of Covid-19 cases
timeFrame: Change from baseline at 6 monhts
measure: Viral neutralization assay
timeFrame: Change from baseline at 1, 3, 5 and 6 months
measure: Serological assay
timeFrame: Change from baseline at 1, 3, 5 and 6 months
measure: Soluble systemic factors
timeFrame: Change from baseline at 1, 3, 5 and 6 months
measure: Lymphocyte investigation
timeFrame: Change from baseline at 1, 3, 5 and 6 months
measure: Cytokine investigation
timeFrame: Change from baseline at 1, 3, 5 and 6 months
Other outcomes:
Locations:
city: Vitória
country: Brazil
facility: Valéria Valim
state: Espírito Santo
Study officials:
References: