SARS-CoV-2 (COVID-19) Vaccine Tolerability and Clinical Outcome Among Hospital Staff

Sponsor

Serge Thal (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05076227

Collaborator

(none)

1,206

Enrollment

Location

Anticipated Duration (Months)

86.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Evaluation of the clinical tolerance after the first and second administration of an mRNA vaccine, and depending on the availability of further vaccines, against SARS-CoV-2 for hospital employees.

Retrospective analysis of available antibodies against SARS-CoV-2 and results of collected nasopharyngeal specimens for the detection of SARS-CoV-2 (PCR and antigen tests) in hospital employees.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV2 Infection Immunisation Reaction Antibody Hypersensitivity Tolerance	Drug: IM injection of vaccination (mRNA vaccination) Drug: IM injection of vaccination (vector based vaccination)

Detailed Description

Employees of the Helios Hospital Hildesheim received a vaccination offer from January 2021 in accordance with the current prioritization.

Taking into account the national vaccination recommendation by the Ständige Impfkommission (STIKO), the mRNA vaccine BNT162b2 (Comirnaty, BioNTech/Pfizer) and the vector-based vaccine AZD1222/ChAdOx1-S (Vaxzevria, AstraZeneca) are used.

Four vaccine-groups can be distinguished:

Group 1 received BNT162b2 with the boost vaccination 3 weeks after the initial vaccination.

Vaccinees of groups 2 and 3 received AZD1222/ChAdOx1-S as prime vaccination and could choose after 12 weeks whether boost vaccination with BNT162b2 or AZD1222/ChAdOx1-S should be carried out. This results in homologous (prime: AZD1222/ChAdOx1-S, boost: AZD1222/ChAdOx1-S) and heterologous (prime: AZD1222/ChAdOx1-S, boost: BNT162b2) vaccine combinations.

Group 4 received BNT162b2 with the boost vaccination 6 weeks after prime vaccination.

All subjects evaluate the vaccination reactions within one week using a standardized questionnaire.

In addition, demographic data (age, gender, occupational group, allergies) are collected, local and systemic vaccination reactions are differentiated and the need for medication and inability to work as a result of vaccination reactions are prospectively recorded.

Independently of this, the vaccinees were offered serial blood samples by the company physician to measure COVID-19-associated antibodies (anti-nucleocapsid and anti-spike).

Three blood samples were taken at 4 weeks, 3 months and 6 months after the boost vaccination.

This study can retrospectively access the data from these blood tests as well as PCR smear results for COVID-19 during the observation period. A corresponding consent to the analysis of the data, previously pseudonymized by the company physician, was given in advance by the study participants.

The prospectively collected data of the questionnaires on reactogenicity are evaluated in combination and relation to the additional and independent data of the company physician.

Data will allow for analysing associations between demographic variables, the reactogenicity, the antibody levels and possible results of the nasopharyngeal swabs.

Study Design

Study Type:

Observational

Actual Enrollment :

1206 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

SARS-CoV-2 Vaccine Tolerability and Clinical Outcome Over Six Months After Completion of Immunisation Among Hospital Staff (HelCoVac - Helios Hildesheim COVID-19 Vaccination Study)

Actual Study Start Date :

Jan 30, 2021

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
BNT162b2/BNT162b2 - 3 wks hospital staff receiving BioNTech as prime vaccination and also receiving BioNTech after 3 weeks as boost vaccination	Drug: IM injection of vaccination (mRNA vaccination) mRNA vaccination Other Names: Cormirnaty (BioNTech/Pfizer)
ChAdOx1/ChAdOx1 - 12 wks hospital staff receiving AstraZeneca as prime vaccination and also receiving AstraZeneca as boost vaccination after 12 weeks	Drug: IM injection of vaccination (vector based vaccination) vector based vaccination Other Names: AZD1222 (AstraZeneca)
ChAdOx1/BNT162b2 - 12 wks hospital staff receiving AstraZeneca as prime vaccination and receiving BioNTech as boost vaccination after 12 weeks	Drug: IM injection of vaccination (mRNA vaccination) mRNA vaccination Other Names: Cormirnaty (BioNTech/Pfizer) Drug: IM injection of vaccination (vector based vaccination) vector based vaccination Other Names: AZD1222 (AstraZeneca)
BNT162b2/BNT162b2 - 6 wks hospital staff receiving BioNTech as prime vaccination and also receiving BioNTech after 6 weeks as boost vaccination	Drug: IM injection of vaccination (mRNA vaccination) mRNA vaccination Other Names: Cormirnaty (BioNTech/Pfizer)

Outcome Measures

Primary Outcome Measures

Do the four cohorts differ in terms of reactogenicity (systemic and/or local vaccine reactions) after the first vaccination? [immediately after first vaccination]
The descriptive data are described by means of frequencies (%/n). The confirmatory analysis is performed using the Chi² test. Since the evaluation is performed at two points in time, the Bonferoni correction is applied here, so that the significance level is α/2=0.025.
Do the four cohorts differ in terms of reactogenicity (systemic and/or local vaccine reactions) after the second vaccination? [immediately after second vaccination]
The descriptive data are described by means of frequencies (%/n). The confirmatory analysis is performed using the Chi² test. Since the evaluation is performed at two points in time, the Bonferoni correction is applied here, so that the significance level is α/2=0.025.
Difference between the four cohorts regarding the antibody of the viral spike protein after 4 weeks [4 weeks after boost vaccination]
The descriptive data are described by means of frequencies (%/n). The confirmatory analysis is performed using the Chi² test. The second primary endpoint is seen independently of the other two endpoints. Therefore, Bonferroni correction is not necessary.
Difference between the four cohorts regarding the antibody of the viral spike protein after 3 months [3 months after boost vaccination]
A statistical evaluation with the continuous data on the antibody is aimed at. However, since it is not clear how many subjects will have a continuous value due to the prevailing Cuf-Off of 2500U/ml until June 30, 2021, the concrete evaluation will be decided by data base lock. The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed by ANOVA with repeated measures and corresponding posthoc tests (for continuous data) or by McNemar-Bowker test for categorical variables (together for 3 and 6 months after the second vaccination). The second primary endpoint is seen independently of the other two endpoints. Therefore, Bonferroni correction is not necessary.
Difference between the four cohorts regarding the antibody of the viral spike protein after 6 months [6 months after boost vaccination]
A statistical evaluation with the continuous data on the antibody is aimed at. However, since it is not clear how many subjects will have a continuous value due to the prevailing Cuf-Off of 2500U/ml until June 30, 2021, the concrete evaluation will be decided by data base lock. The descriptive data are described by frequencies (%/n) and the continuous data by corresponding position parameters (median, interquartile range). The confirmatory analysis is performed by ANOVA with repeated measures and corresponding posthoc tests (for continuous data) or by McNemar-Bowker test for categorical variables (together for 3 and 6 months after the second vaccination). The second primary endpoint is seen independently of the other two endpoints. Therefore, Bonferroni correction is not necessary.

Secondary Outcome Measures

Differences between the 4 groups after first vaccination regarding a. the individual local vaccination reactions? b. the individual systemic vaccination reactions? c. the number or percentage of vaccination reactions? [immediately after first vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Differences between the 4 groups after second vaccination regarding a. the individual local vaccination reactions? b. the individual systemic vaccination reactions? c. the number or percentage of vaccination reactions? [immediately after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a difference between the four cohorts regarding the severity of vaccination reactions? [immediately after first vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a difference between the four cohorts regarding the severity of vaccination reactions? [immediately after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Do the four cohorts differ with respect to the temporal occurrence of vaccination reactions? [immediately after first vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Do the four cohorts differ with respect to the temporal occurrence of vaccination reactions? [immediately after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a difference between the four cohorts regarding the use of medication due to vaccination reactions? [first and second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Do the four cohorts differ with regard to the need for a certificate of incapacity for work due to vaccination reactions? [immediately after first vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Are there differences regarding the job groups and the vaccination week days? [immediately after first vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Do the four cohorts differ with regard to the need for a certificate of incapacity for work due to vaccination reactions? [immediately after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Are there differences regarding the job groups and the vaccination week days? [immediately after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Are there differences within the cohorts regarding vaccination reactions in subjects with a known allergy? [immediately after first vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Are there differences within the total population regarding vaccination reactions in subjects with a known allergy? [immediately after first vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Are there differences within the cohorts regarding vaccination reactions in subjects with a known allergy? [immediately after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Are there differences within the total population regarding vaccination reactions in subjects with a known allergy? [immediately after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a correlation within cohorts or within the overall population at four weeks regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI? [4 weeks after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. Spearman's correlation is calculated.
Do the variables listed above have an influence on the level of antibody? [4 weeks after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. To investigate a potential influence of the variables, a logistic regression is performed if necessary.
Is there a correlation within cohorts or within the overall population at 3 months regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI? [3 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. Spearman's correlation is calculated.
Is there a correlation within cohorts or within the overall population at 6 months regarding the level of antibody and the a. Extent of vaccine response (local, systemic, local & systemic, none)? b. Gender? c. Age? d. BMI? [6 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. Spearman's correlation is calculated.
Do the variables listed above have an influence on the level of antibody? [3 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. To investigate a potential influence of the variables, a logistic regression is performed if necessary.
Do the variables listed above have an influence on the level of antibody? [6 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. To investigate a potential influence of the variables, a logistic regression is performed if necessary.
Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at three months from baseline within the four cohorts? [3 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at six months from baseline within the four cohorts? [6 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at three months from baseline between the four cohorts? [3 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a statistically significant or clinically relevant difference between the (drop in) antibodies at six months from baseline between the four cohorts? [6 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Are there any subjects within the six-month follow-up period who had proven SARS Cov2 infection? (Comparison between groups) [6 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively. The analysis is performed using appropriate tests such as Fisher's exact test, Chi² test, Mann-Whitney U test or Krukal-Wallis test.
Is there a correlation within the overall population between the level of antibody and detected SARS Cov2 infection? [3 months and 6 months after second vaccination]
For the secondary endpoints, frequencies (%/n) for categorical data and corresponding measures of location (median, interquartile range) for continuous data are used descriptively.