Ignite Creation Date:
2024-05-06 @ 3:28 PM
Last Modification Date:
2024-10-26 @ 1:50 PM
Study NCT ID:
NCT04648800
Status:
UNKNOWN
Last Update Posted:
2020-12-02
First Post:
2020-10-18
Brief Title:
Clinical Trial Evaluating the Effect of BCG Vaccination on the Incidence and Severity of SARS-CoV-2 Infections Among Healthcare Professionals During the COVID-19 Pandemic in Poland
Sponsor:
Hanna Czajka
Organization:
University of Rzeszow
Study Overview
Official Title:
A Multi-centre Randomised Double-blind Placebo-controlled Phase III Clinical Trial Evaluating the Effect of BCG Vaccination on the Incidence and Severity of SARS-CoV-2 Infections Among Healthcare Professionals During the COVID-19 Pandemic in Poland
Status:
UNKNOWN
Status Verified Date:
2020-11
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Countries that have not carried out universal mass vaccination against tuberculosis BCG have been shown to have higher incidence and death rates due to COVID-19 than countries with mass long-term BCG immunization programmes
The aim of the study is to answer the following questions
1 Does BCG vaccination affect the course of COVID-19 number of casesdeathsseverity of symptoms
2 Will the course of COVID-19 be milder among subjects with a negative TB skin test PPD RT 23 SSI after an additional dose of BCG than in case of non-vaccinated subjects
3 Do people with a positive TB skin test have a milder course of COVID-19 infection than people with a negative test result
A multicenter randomized partially blinded placebo-controlled study will be conducted in RzeszowKrakow KatowiceWarsaw on a group of 1000 volunteers health care workers according to the following schedule V 0-1 inclusioninformed consentinterview V2 administration of TB skin testanti-SARS-CoV-2 IgG testserum banking V3 TB skin test TST interpretation and subjects division into three groups I positive TST - observation II negative TST- BCG-10 vaccination III negative TST - placebo Division into groups II and III based on randomisation V4 serum banking Parallel beginning from V3 weekly telephone monitoring participants health status In case of COVID-19 symptoms a nasopharyngeal swab to confirm SARS-CoV-2 infection serum banking V5 3 months after vaccination at the end of the study historyanti-SARS-CoV-2 IgG test serum banking
Statistical analysis - comparison of the course of COVID-19 in groups I with positive TST observation II with negative TST BCG III with negative TST placebo - should demonstrate whether mass BCG vaccination has an impact on the incidence and course of COVID-19
to measure the level of cytokines involved in cell-mediated immunity process
The aim of the study is to answer the following questions
1 Does BCG vaccination affect the course of COVID-19 number of casesdeathsseverity of symptoms
2 Will the course of COVID-19 be milder among subjects with a negative TB skin test PPD RT 23 SSI after an additional dose of BCG than in case of non-vaccinated subjects
3 Do people with a positive TB skin test have a milder course of COVID-19 infection than people with a negative test result
A multicenter randomized partially blinded placebo-controlled study will be conducted in RzeszowKrakow KatowiceWarsaw on a group of 1000 volunteers health care workers according to the following schedule V 0-1 inclusioninformed consentinterview V2 administration of TB skin testanti-SARS-CoV-2 IgG testserum banking V3 TB skin test TST interpretation and subjects division into three groups I positive TST - observation II negative TST- BCG-10 vaccination III negative TST - placebo Division into groups II and III based on randomisation V4 serum banking Parallel beginning from V3 weekly telephone monitoring participants health status In case of COVID-19 symptoms a nasopharyngeal swab to confirm SARS-CoV-2 infection serum banking V5 3 months after vaccination at the end of the study historyanti-SARS-CoV-2 IgG test serum banking
Statistical analysis - comparison of the course of COVID-19 in groups I with positive TST observation II with negative TST BCG III with negative TST placebo - should demonstrate whether mass BCG vaccination has an impact on the incidence and course of COVID-19
to measure the level of cytokines involved in cell-mediated immunity process
Detailed Description:
Trial design
The multicentre randomised double-blind placebo-controlled trial will be conducted in five centres Rzeszów Kraków Katowice Warsaw 2 centres in a group of 1000 volunteers health care workers physicians nurses midwives paramedics laboratory diagnosticians electroradiology technicians physiotherapists nutritionists and orderlies both women and men aged 25 years and employed in health care facilities in the above-mentioned cities and provinces
Planned duration of the trial
2-4 weeks -recruitment inclusion in the trial RT 23 testing BCG-10 vaccination 3 months - observation after vaccination 18 months calculated from the date of trial initiation visit no 0 during this period the subjects are to provide the Research Team with telephone information about possible hospitalisations and other unexpected sudden or significant changes in health
Recruitment period
Sending invitations to participate in the trial to the healthcare professionals involved as well as providing the subjects with Information for trial participants leaflets and electronic Informed Consent forms
Inclusion in the trial visit No0 - V0
obtaining informed consent to participate in the trial by exchanging electronic information and declarations of intent between the centre investigator and the individual declaring readiness to participate in research with double verification of the subject identity e-mailSMS which is intended to limit direct contacts during the period of COVID-19 epidemic risk
Inclusion in the trial visit No1 - V1
Investigator-subject telephone contact in the days following V0 or directly during the same day
remote verification of the subject according to the inclusion and exclusion criteria history taking regarding demographic characteristics health status and previous BCG vaccinations
setting the date of the RT23 test place day time to minimise the number of direct contacts between the research team and the subjects in accordance with the current epidemic recommendations
after the visit the investigator enters the information obtained into the e-CRF system The details concerning the visit and the scope of information collected are to be contained in V1 and V01 cards
after the visit the investigator enters its results into the medical documentation and e-CRF system
Running the RT 23 test visit No2 - V2
direct contact following the telephone contact to confirm the subjects health condition
temperature measurement non-contact thermometer blood sampling 5 ml for determinations of IgG SARS-CoV-2 antibodies and cytokine levels
photographing the scars after BCG vaccination on the left forearm of the subject without the details of appearance the photographs are stored in the electronic documentation with the number assigned to a particular subject
RT 23 trial initiation
providing the subject with the written informed consent form participant card as well as the card of contacts thermometer and pregnancy test females in a sealed plastic envelope
the visit will be carried out in accordance with the procedures in force in departments of infectious diseases
setting the date date and time of the third visit- after 72 hours
after the visit the investigator will enter its results into the medical documentation and e-CRF system
RT23 test reading and BCG -10 vaccination visit No3-V3
the direct visit preceded by the telephone contact to confirm the subjects health status
before the visit the female subjects perform a pregnancy test in the morning hours those with positive results are excluded from the trial
temperature measurement non-contact thermometer
the visit will be carried out in accordance with the procedures in force in departments of infectious diseases
reading of the tuberculin test run during visit 2 according to the criteria and photographing the post-test induration on the left arm of the subject for documentation purposes no appearance details the photos are stored in the electronic documentation marked with the number given to a particular study subject
Positive subjects
are assigned to Group I are not randomised and are not vaccinated against tuberculosis
are subjected to a weekly remote medical follow-ups in agreement with the telephone contact card until the trial completion 3 months from the date of visit 3 of the last subject the follow ups are conducted by the investigator a member of the research team not participating in visit 3
when the RT23 test indicates a strongly positive result induration diameter 15 mm the subject is informed to contact hisher family doctor to obtain a referral to a pulmonary outpatient clinic
Negative subjects
undergo a physical examination before vaccination performed by the doctor investigator
are remotely randomised by the e-CRF IT system to Group II receiving BCG-10 or to placebo Group III control The subject must not be informed about the group heshe belongs to
receive BCG-10 or a placebo in intradermal injections performed by a trained nurse with appropriate professional experience
undergo weekly remote medical observations carried out by the investigator not involved in visit 3 according to the telephone contact card until the trial completion 3 months from the date of visit 3 of the last subject Due to trial blindness the team a doctor and nurse participating in visits 2 V2 and 3 V3 as unblinded staff is excluded from further contacts with trial subjects and from participating in the trial
After the visit the investigator enters its results into the medical documentation and the e-CRF system
In the medical records of visit 3 written and electronic the result of randomization is not disclosed
After visit 3 the division of subjects into Groups II and III randomisation is recorded only in separate written records the physician participating in visit 2 and 3 sends the documentation to the leading centre after the end of visit 3 where it is stored and fully protected against access of blinded personnel
Blood collection - visit No 4 V4
within 6-8 weeks after visit 3 all subjects are invited by telephone to the place designated by the Principal Investigator to take 5 ml blood samples to determine the levels of cytokines
blood collection is carried out by a member of the research team appointed by the Principal Investigator
after the visit the investigator enters its results into the e-CRF system
Blood collection - visit No 5 V5
three months after visit 3 all subjects are invited by telephone to the place designated by the Principal Investigator to take 5 ml blood samples to determine SARS-CoV-2 IgG antibodies and cytokine levels
blood collection is carried out by a member of the research team appointed by the Principal Investigator
after the visit the investigator enters its results into the medical documentation and the e-CRF system
Remote phone visit
carried out for a period of three months between visit 3 V3 and visit 5 V5 once a week during this visit the physician member of the research team asks questions according to the attached phone contact card
Interventional visit
will be carried out between visit 3 and visit 5 when the symptoms determined in the telephone Contact card appear to indicate a possible SARS-CovV-2 infection
the trial subject contacts by telephone the investigator conducting a weekly remote medical observation and if the score 3 is obtained during the telephone evaluation of health the mobile team is deployed to the subject
the ambulance takes a swab from the subjects nasopharynx and collects 5 ml of blood for cytokine determinations to confirm the infection with this virus or otherwise The visit will be carried out at the subjects place of residence and the material collected will be delivered to a respective analytical laboratory
after the visit the investigator will enter its results into the medical documentation and the e-CRF system
Moreover
each subject may contact the research centre by phone 24 hours a day 7 days a week
each subject may withdraw from the trial at any time
when the telephone contact with the subject is infeasible the research team may use the reserve contact indicated by the subject or contact the hospital attending the subject
if the subject develops the symptoms of COVID-19 during the trial heshe has to adhere to the generally applicable rules
at the end of the study all subjects in groups II and III will be notified individually and confidentially whether they have received BCG-10 or placebo
when a preliminary result indicates the significant benefits of additional BCG vaccination an additional dose of BCG-10 will be offered to all non-vaccinated subjects
Statistical analysis Statistical analysis will be conducted using MedCalc v177 software The quantitative variables will be presented as an arithmetic mean and standard deviation variables with a normal distribution or median and interquartile range variables with a non-normal distribution a skewed distribution The distribution will be assessed using the Shapiro-Wilk test The qualitative variables will be presented as an absolute value and percentage The inter-group differences for quantitative variables will be evaluated by the Students t-test or analysis of variance independent samples variables with a normal distribution and the Mann-Whitney U or Kruskal-Wallis test independent samples skewed variables
In cases where significant inter-group differences have been demonstrated based on the ANOVA or Kruskal-Wallis test a post-hoc analysis will be performed The significance of differences for quantitative dependent variables will be assessed applying the Student t-test for dependent samples or the non-parametric equivalent of variance analysis or the Wilcoxon signed-rank or Friedmans rank test depending on the number of groups and the distribution For unrelated qualitative variables the chi-squared test or Fishers exact test will be used while for related variables the McNemars test will be applied The correlation between inter-qualitative variables will be analysed using the Pearson correlation analysis or Spearmans rank correlation For selected qualitative dependencies for quality dichotomous variables the odds ratios or relative risk factors and their 95 confidence intervals will be calculated The results of simple analyses will be the basis for advanced statistical analysis methods ie logistic regression models or multiple regression analyses Models will include variables with p01 in simple analysis will be included in the models mentioned above Moreover the odds ratios together with 95 confidence intervals logistic regression or regression coefficients with their standard error multiple regression will be estimated Finally p005 will be considered statistically significant
Minimum number of trial subjects
A Assuming that 50 of individuals have negative tuberculin test results when alpha005 and measurement precision5 a group of at least 384 subjects 400 should be recruited Assuming a 10 loss of subjects between the initiation and reading of the tuberculin test the group subjected to the tuberculin test should contain at least 450 people
B Assuming a 10 difference in endpoint occurrence disease when alpha005 is expected at least 193 individuals in each group 200 should be examined Given the loss to follow -up of 10 each group study and control should include at least 220 individuals
C In conclusion considering all the above calculations at least 880 individuals 900 should be included in the trial Given that 10 of subjects will not give their informed consent to participate in the trial at least 990 individuals 1000 should be invited to the project
Note Six weeks after the inclusion of the last subject the number of serious adverse events SAEs in each group is to be analysed in order to decide whether to continue the follow-up or to administer the BCG vaccine to all non-vaccinated subjects
Data analysed
1 Incidence and deaths rates in the study group
2 Additionally
documented SARS-CoV-2 infection
duration of symptoms
types of symptoms and their frequency
average duration of domestic isolation
maintenance of body temperature 375oC in the ranges of
1 375C-380C
2 381C-390C
3 more than 39C
in the case of hospitalisation length of treatment including possible ICU stay ventilator therapy complications death
3 group characteristics
date of inclusion date of signing informed consent to participate in the trial
age month year of birth
gender
body weight height BMI
province of residence Podkarpackie Małopolska Silesian Mazovian
workplace department ER outpatient clinic analytical laboratory
profession physician nurse midwife paramedic laboratory diagnostician nutritionist electroradiology technician physiotherapist orderly
working hours per month number of jobs during the pandemic
shift work YESNO
percentage of hours of direct contact with the patient four intervals 25 25-50 50-75 75
cardiovascular diseases hypertension ischaemic heart disease post-myocardial infarct condition atrial fibrillation chronic heart failure others - which ones
respiratory diseases asthma chronic obstructive pulmonary disease COPD interstitial lung disease others- which ones
diseases of the nervous system epilepsy post-stroke condition polyneuropathy others- which ones
diseases of the osteoarticular system osteoarthritis rheumatoid arthritis others- which ones
diseases of the gastrointestinal system liver diseases - list them bowel diseases- list them pancreatic diseases- list them others which ones
kidney disease chronic kidney disease kidney stones others- which ones
diabetes type 1 type 2 dietinsulin
autoimmune diseases which ones
other chronic diseases which ones
neoplastic diseases which ones how treated when
smoking pack-year E-cigarettes years
allergies which ones
BCG vaccinations to this day
Laboratory tests during the trial
1 standard planned blood test during visit 2 running the RT23 test -collection of 5 ml of blood determination of the presence of SARS-CoV-2 IgG antibodies determination of the level of cytokines regulating cellular immunity - hereinafter referred to as the cytokine level
2 within 6-8 weeks after BCG vaccination collection of 5 ml of blood for cytokine level determinations
3 after the completion of follow-ups 3 months after the last study participant was included collection of 5 ml of blood for determination of IgG antibody levels SARS-CoV-2 virus and cytokine levels
4 if COVID-19 symptoms occur in the subject
1 the subject eligible for hospitalisation will be urgently emergently hospitalised due to COVID-19 and tested according to the procedures in force in the hospital moreover each subject will receive an identifier similar to ID with information about participation in the trial and a request to the personnel assuming care of the subject to inform the research team and secure samples 5 ml of blood for cytokine determination and a swab from the nasopharynx for the SARS-CovV-2 genetic material testing
2 in the case of the subject not eligible for hospitalisations with symptoms suggestive of the infection but not requiring hospitalisation symptoms and their duration will be noted and during the intervention visit 5 ml of blood will be sampled for cytokine determinations and a nasopharyngeal swab will be taken for testing whether SARS-CoV-2 genetic material is present or otherwise The material will be collected at the subjects home in accordance with the safety procedure
Methodology of laboratory tests Laboratory blood tests for determinations of SARS-CoV-2 IgG antibodies and cytokine levels will be carried out
Procedure - collection and transport of material to the laboratory preparing it for banking
Collection of nasopharyngeal swabs for SARS CoV-2 genetic material testing using the RT-qPCR test and blood sampling to assess cytokine andor IgG levels
Criteria for completion of the trial
According to its program the trial will last for a period of 3 months from the date of visit No 3 administration of the vaccine to the date of visit 5 blood collection for determinations of IgG SARS-CoV-2 antibodies and cytokine levels
Over the next 15 months the subjects will be asked to provide the Research Team with telephone information about possible hospitalizations and other unexpected sudden or significant changes in their health
The trial will be completed after the last visit of the last subject and after the results serological and genetic tests PCR-SARS are available approximately 8 months after its initiation
The observation of possible SAEs reported by the subjects will be completed 18 months after the commencement of the trial
The multicentre randomised double-blind placebo-controlled trial will be conducted in five centres Rzeszów Kraków Katowice Warsaw 2 centres in a group of 1000 volunteers health care workers physicians nurses midwives paramedics laboratory diagnosticians electroradiology technicians physiotherapists nutritionists and orderlies both women and men aged 25 years and employed in health care facilities in the above-mentioned cities and provinces
Planned duration of the trial
2-4 weeks -recruitment inclusion in the trial RT 23 testing BCG-10 vaccination 3 months - observation after vaccination 18 months calculated from the date of trial initiation visit no 0 during this period the subjects are to provide the Research Team with telephone information about possible hospitalisations and other unexpected sudden or significant changes in health
Recruitment period
Sending invitations to participate in the trial to the healthcare professionals involved as well as providing the subjects with Information for trial participants leaflets and electronic Informed Consent forms
Inclusion in the trial visit No0 - V0
obtaining informed consent to participate in the trial by exchanging electronic information and declarations of intent between the centre investigator and the individual declaring readiness to participate in research with double verification of the subject identity e-mailSMS which is intended to limit direct contacts during the period of COVID-19 epidemic risk
Inclusion in the trial visit No1 - V1
Investigator-subject telephone contact in the days following V0 or directly during the same day
remote verification of the subject according to the inclusion and exclusion criteria history taking regarding demographic characteristics health status and previous BCG vaccinations
setting the date of the RT23 test place day time to minimise the number of direct contacts between the research team and the subjects in accordance with the current epidemic recommendations
after the visit the investigator enters the information obtained into the e-CRF system The details concerning the visit and the scope of information collected are to be contained in V1 and V01 cards
after the visit the investigator enters its results into the medical documentation and e-CRF system
Running the RT 23 test visit No2 - V2
direct contact following the telephone contact to confirm the subjects health condition
temperature measurement non-contact thermometer blood sampling 5 ml for determinations of IgG SARS-CoV-2 antibodies and cytokine levels
photographing the scars after BCG vaccination on the left forearm of the subject without the details of appearance the photographs are stored in the electronic documentation with the number assigned to a particular subject
RT 23 trial initiation
providing the subject with the written informed consent form participant card as well as the card of contacts thermometer and pregnancy test females in a sealed plastic envelope
the visit will be carried out in accordance with the procedures in force in departments of infectious diseases
setting the date date and time of the third visit- after 72 hours
after the visit the investigator will enter its results into the medical documentation and e-CRF system
RT23 test reading and BCG -10 vaccination visit No3-V3
the direct visit preceded by the telephone contact to confirm the subjects health status
before the visit the female subjects perform a pregnancy test in the morning hours those with positive results are excluded from the trial
temperature measurement non-contact thermometer
the visit will be carried out in accordance with the procedures in force in departments of infectious diseases
reading of the tuberculin test run during visit 2 according to the criteria and photographing the post-test induration on the left arm of the subject for documentation purposes no appearance details the photos are stored in the electronic documentation marked with the number given to a particular study subject
Positive subjects
are assigned to Group I are not randomised and are not vaccinated against tuberculosis
are subjected to a weekly remote medical follow-ups in agreement with the telephone contact card until the trial completion 3 months from the date of visit 3 of the last subject the follow ups are conducted by the investigator a member of the research team not participating in visit 3
when the RT23 test indicates a strongly positive result induration diameter 15 mm the subject is informed to contact hisher family doctor to obtain a referral to a pulmonary outpatient clinic
Negative subjects
undergo a physical examination before vaccination performed by the doctor investigator
are remotely randomised by the e-CRF IT system to Group II receiving BCG-10 or to placebo Group III control The subject must not be informed about the group heshe belongs to
receive BCG-10 or a placebo in intradermal injections performed by a trained nurse with appropriate professional experience
undergo weekly remote medical observations carried out by the investigator not involved in visit 3 according to the telephone contact card until the trial completion 3 months from the date of visit 3 of the last subject Due to trial blindness the team a doctor and nurse participating in visits 2 V2 and 3 V3 as unblinded staff is excluded from further contacts with trial subjects and from participating in the trial
After the visit the investigator enters its results into the medical documentation and the e-CRF system
In the medical records of visit 3 written and electronic the result of randomization is not disclosed
After visit 3 the division of subjects into Groups II and III randomisation is recorded only in separate written records the physician participating in visit 2 and 3 sends the documentation to the leading centre after the end of visit 3 where it is stored and fully protected against access of blinded personnel
Blood collection - visit No 4 V4
within 6-8 weeks after visit 3 all subjects are invited by telephone to the place designated by the Principal Investigator to take 5 ml blood samples to determine the levels of cytokines
blood collection is carried out by a member of the research team appointed by the Principal Investigator
after the visit the investigator enters its results into the e-CRF system
Blood collection - visit No 5 V5
three months after visit 3 all subjects are invited by telephone to the place designated by the Principal Investigator to take 5 ml blood samples to determine SARS-CoV-2 IgG antibodies and cytokine levels
blood collection is carried out by a member of the research team appointed by the Principal Investigator
after the visit the investigator enters its results into the medical documentation and the e-CRF system
Remote phone visit
carried out for a period of three months between visit 3 V3 and visit 5 V5 once a week during this visit the physician member of the research team asks questions according to the attached phone contact card
Interventional visit
will be carried out between visit 3 and visit 5 when the symptoms determined in the telephone Contact card appear to indicate a possible SARS-CovV-2 infection
the trial subject contacts by telephone the investigator conducting a weekly remote medical observation and if the score 3 is obtained during the telephone evaluation of health the mobile team is deployed to the subject
the ambulance takes a swab from the subjects nasopharynx and collects 5 ml of blood for cytokine determinations to confirm the infection with this virus or otherwise The visit will be carried out at the subjects place of residence and the material collected will be delivered to a respective analytical laboratory
after the visit the investigator will enter its results into the medical documentation and the e-CRF system
Moreover
each subject may contact the research centre by phone 24 hours a day 7 days a week
each subject may withdraw from the trial at any time
when the telephone contact with the subject is infeasible the research team may use the reserve contact indicated by the subject or contact the hospital attending the subject
if the subject develops the symptoms of COVID-19 during the trial heshe has to adhere to the generally applicable rules
at the end of the study all subjects in groups II and III will be notified individually and confidentially whether they have received BCG-10 or placebo
when a preliminary result indicates the significant benefits of additional BCG vaccination an additional dose of BCG-10 will be offered to all non-vaccinated subjects
Statistical analysis Statistical analysis will be conducted using MedCalc v177 software The quantitative variables will be presented as an arithmetic mean and standard deviation variables with a normal distribution or median and interquartile range variables with a non-normal distribution a skewed distribution The distribution will be assessed using the Shapiro-Wilk test The qualitative variables will be presented as an absolute value and percentage The inter-group differences for quantitative variables will be evaluated by the Students t-test or analysis of variance independent samples variables with a normal distribution and the Mann-Whitney U or Kruskal-Wallis test independent samples skewed variables
In cases where significant inter-group differences have been demonstrated based on the ANOVA or Kruskal-Wallis test a post-hoc analysis will be performed The significance of differences for quantitative dependent variables will be assessed applying the Student t-test for dependent samples or the non-parametric equivalent of variance analysis or the Wilcoxon signed-rank or Friedmans rank test depending on the number of groups and the distribution For unrelated qualitative variables the chi-squared test or Fishers exact test will be used while for related variables the McNemars test will be applied The correlation between inter-qualitative variables will be analysed using the Pearson correlation analysis or Spearmans rank correlation For selected qualitative dependencies for quality dichotomous variables the odds ratios or relative risk factors and their 95 confidence intervals will be calculated The results of simple analyses will be the basis for advanced statistical analysis methods ie logistic regression models or multiple regression analyses Models will include variables with p01 in simple analysis will be included in the models mentioned above Moreover the odds ratios together with 95 confidence intervals logistic regression or regression coefficients with their standard error multiple regression will be estimated Finally p005 will be considered statistically significant
Minimum number of trial subjects
A Assuming that 50 of individuals have negative tuberculin test results when alpha005 and measurement precision5 a group of at least 384 subjects 400 should be recruited Assuming a 10 loss of subjects between the initiation and reading of the tuberculin test the group subjected to the tuberculin test should contain at least 450 people
B Assuming a 10 difference in endpoint occurrence disease when alpha005 is expected at least 193 individuals in each group 200 should be examined Given the loss to follow -up of 10 each group study and control should include at least 220 individuals
C In conclusion considering all the above calculations at least 880 individuals 900 should be included in the trial Given that 10 of subjects will not give their informed consent to participate in the trial at least 990 individuals 1000 should be invited to the project
Note Six weeks after the inclusion of the last subject the number of serious adverse events SAEs in each group is to be analysed in order to decide whether to continue the follow-up or to administer the BCG vaccine to all non-vaccinated subjects
Data analysed
1 Incidence and deaths rates in the study group
2 Additionally
documented SARS-CoV-2 infection
duration of symptoms
types of symptoms and their frequency
average duration of domestic isolation
maintenance of body temperature 375oC in the ranges of
1 375C-380C
2 381C-390C
3 more than 39C
in the case of hospitalisation length of treatment including possible ICU stay ventilator therapy complications death
3 group characteristics
date of inclusion date of signing informed consent to participate in the trial
age month year of birth
gender
body weight height BMI
province of residence Podkarpackie Małopolska Silesian Mazovian
workplace department ER outpatient clinic analytical laboratory
profession physician nurse midwife paramedic laboratory diagnostician nutritionist electroradiology technician physiotherapist orderly
working hours per month number of jobs during the pandemic
shift work YESNO
percentage of hours of direct contact with the patient four intervals 25 25-50 50-75 75
cardiovascular diseases hypertension ischaemic heart disease post-myocardial infarct condition atrial fibrillation chronic heart failure others - which ones
respiratory diseases asthma chronic obstructive pulmonary disease COPD interstitial lung disease others- which ones
diseases of the nervous system epilepsy post-stroke condition polyneuropathy others- which ones
diseases of the osteoarticular system osteoarthritis rheumatoid arthritis others- which ones
diseases of the gastrointestinal system liver diseases - list them bowel diseases- list them pancreatic diseases- list them others which ones
kidney disease chronic kidney disease kidney stones others- which ones
diabetes type 1 type 2 dietinsulin
autoimmune diseases which ones
other chronic diseases which ones
neoplastic diseases which ones how treated when
smoking pack-year E-cigarettes years
allergies which ones
BCG vaccinations to this day
Laboratory tests during the trial
1 standard planned blood test during visit 2 running the RT23 test -collection of 5 ml of blood determination of the presence of SARS-CoV-2 IgG antibodies determination of the level of cytokines regulating cellular immunity - hereinafter referred to as the cytokine level
2 within 6-8 weeks after BCG vaccination collection of 5 ml of blood for cytokine level determinations
3 after the completion of follow-ups 3 months after the last study participant was included collection of 5 ml of blood for determination of IgG antibody levels SARS-CoV-2 virus and cytokine levels
4 if COVID-19 symptoms occur in the subject
1 the subject eligible for hospitalisation will be urgently emergently hospitalised due to COVID-19 and tested according to the procedures in force in the hospital moreover each subject will receive an identifier similar to ID with information about participation in the trial and a request to the personnel assuming care of the subject to inform the research team and secure samples 5 ml of blood for cytokine determination and a swab from the nasopharynx for the SARS-CovV-2 genetic material testing
2 in the case of the subject not eligible for hospitalisations with symptoms suggestive of the infection but not requiring hospitalisation symptoms and their duration will be noted and during the intervention visit 5 ml of blood will be sampled for cytokine determinations and a nasopharyngeal swab will be taken for testing whether SARS-CoV-2 genetic material is present or otherwise The material will be collected at the subjects home in accordance with the safety procedure
Methodology of laboratory tests Laboratory blood tests for determinations of SARS-CoV-2 IgG antibodies and cytokine levels will be carried out
Procedure - collection and transport of material to the laboratory preparing it for banking
Collection of nasopharyngeal swabs for SARS CoV-2 genetic material testing using the RT-qPCR test and blood sampling to assess cytokine andor IgG levels
Criteria for completion of the trial
According to its program the trial will last for a period of 3 months from the date of visit No 3 administration of the vaccine to the date of visit 5 blood collection for determinations of IgG SARS-CoV-2 antibodies and cytokine levels
Over the next 15 months the subjects will be asked to provide the Research Team with telephone information about possible hospitalizations and other unexpected sudden or significant changes in their health
The trial will be completed after the last visit of the last subject and after the results serological and genetic tests PCR-SARS are available approximately 8 months after its initiation
The observation of possible SAEs reported by the subjects will be completed 18 months after the commencement of the trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2020-002111-22 | EUDRACT_NUMBER | None | None |