Effectiveness, Immunogenicity and Safety of the Second Booster Dose of the Vaccine Against COVID-19 in the Elderly

COVID-19 Clinical Trial

— Plus_Booster  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05283902
• Other study ID #: FUES05
• Status: Not yet recruiting
• Start date: March 19, 2022
• Est. completion date: October 2022

Study information

• Verified date: March 2022
• Source: Federal University of Espirito Santo
• Contact: Valeria Valim, PhD
• Phone: 2733157899
• Email: val.valim[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 490000
• Est. completion date: October 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Vaccine Adverse Reaction

Intervention

Biological:
• ChAdOx1 nCoV-19 or Comirnaty or Janssen COVID-19 Vaccine
In a Technical Note, the State of Espírito Santo decided to recommend the application of the fourth dose with vaccines using messenger RNA (mRNA) technology or viral vector vaccine, for all people aged 60 years or older, with an interval of 90 days from of the third dose, considering that, while there is no availability of vaccines adapted to the new variants, boosters with available vaccines are still the most appropriate ways to prevent hospitalization and deaths.

Locations

Country	Name	City	State
Brazil	Valéria Valim	Vitória	Espírito Santo

Sponsors (3)

Lead Sponsor	Collaborator
Federal University of Espirito Santo	Instituto René Rachou/Fiocruz, Secretaria de Estado da Saúde do Espírito Santo - SESA

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of hospital admissions	number of hospital admissions for covid-19 recorded in the "e-SUS notifica"	Change from baseline at 6 months
Primary	Number of adverse events	Surveillance of adverse post-vaccine events (PVAE) and adverse events of special interest (EAIE) recorded in the "e-SUS notifica"	Change from baseline at 1 month
Secondary	number of deaths	Number of deaths with specific ICD for covid-19 recorded in the "e-SUS notifica"	Change from baseline at 6 months
Secondary	number of Covid-19 cases	number of Covid-19 cases confirmed by RT-PCR recorded in the "e-SUS notifica"	Change from baseline at 6 monhts
Secondary	Viral neutralization assay	Neutralizing antibody titers will be expressed by the ability of antibodies to neutralize up to 50% the number of plaques (PRNT50). Title > 1:50 will be considered positive.	Change from baseline at 1, 3, 5 and 6 months
Secondary	Serological assay	Serological test by chemiluminescence for qualitative and quantitative determination of specific IgG antibodies against the nucleocapsid protein of SARS-Cov-2. Results are expressed in U/mL and data interpretation will be done as follows: <0.8 U/mL = non-reactive sample; =0.8 U/mL = reactive sample.	Change from baseline at 1, 3, 5 and 6 months
Secondary	Soluble systemic factors	Dosage of soluble systemic factors (chemokines, cytokines and growth factors). Results will be expressed in pg/ml.	Change from baseline at 1, 3, 5 and 6 months
Secondary	Lymphocyte investigation	Investigation of memory T and B lymphocytes. The results will be expressed in percentage positive frequency for a specific cell phenotype.	Change from baseline at 1, 3, 5 and 6 months
Secondary	Cytokine investigation	Investigation of intracytoplasmic cytokines. The results will be expressed in percentage positive frequency for a specific cell phenotype.	Change from baseline at 1, 3, 5 and 6 months