Trial of 2nd Booster Dose of COVID-19 Vaccine
Primary Purpose
COVID-19
Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Invitation to get a 2nd booster dose of COVID-19 vaccine
Sponsored by
About this trial
This is an interventional prevention trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
- Aged between 45 and 64 years
- Registered in the Norwegian national population register
- Have received three doses of a COVID-19 vaccine, with the last dose received at least four months ago.
- Have not previously been offered or recommended a 4th dose for medical reasons
Exclusion Criteria:
- Persons who have already been offered a 4th COVID-19 vaccine dose.
- Persons in whom COVID-19 vaccination is contraindicated as per the vaccines' Summary of Product Characteristics (SPC).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Intervention groups: Invitation to get 2nd booster
Control group: No invitation to get 2nd booster
Arm Description
Participants in the intervention group will receive an invitation to get a 2nd COVID-19 booster dose. Those who accept the invitation to be vaccinated will receive the vaccine through their municipality's vaccination service.
The control group will receive no intervention.
Outcomes
Primary Outcome Measures
Severe COVID-19
Hospitalization or death caused by COVID-19 starting on day 22 after the invitation is sent to the intervention group.
Secondary Outcome Measures
Hospitalization or death
Hospitalization or death from all causes
Health care utilization
Health care utilization and use of prescription medication related to COVID-19
COVID-19 infection
Registered COVID-19 infection
Health care utilization related to potential side effects
Health care utilization related to potential side effects of the COVID-19 vaccine (e.g., myocarditis)
Infection, hospitalization or death
Infection, hospitalization or death in a period of 12 months starting from the date of receiving the 1st booster dose
Full Information
NCT ID
NCT05539703
First Posted
September 13, 2022
Last Updated
September 14, 2022
Sponsor
Norwegian Institute of Public Health
1. Study Identification
Unique Protocol Identification Number
NCT05539703
Brief Title
Trial of 2nd Booster Dose of COVID-19 Vaccine
Official Title
The Effectiveness of Offering a 2nd Booster Dose of COVID-19 Vaccine on Preventing Severe COVID-19; A Register-based Randomized Trial (RRCT)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2022 (Anticipated)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
June 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Norwegian Institute of Public Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Background Recent studies indicate that a 2nd booster dose is associated with lower risk of severe COVID-19. The studies are based on Israeli registry data, comparing outcomes among individuals who have taken the booster, or not. Interpreting the findings from such non-experimental studies is challenging - there are likely systematic differences between those who accept the offer to take a booster dose, and those who do not.
Aim Determine the effect of offering vaccination with a 2nd COVID-19 booster dose on severe COVID-19, measured by hospitalization and death caused by COVID-19.
Methods Intervention group: A random sample drawn from the whole population aged 45-64 years with 3 doses of COVID-19 vaccine will receive a personal offer to receive the 4th dose of a COVID-19 vaccine in their municipality.
Control group: The rest of the population aged 45-64 with 3 doses, who will receive no such offer.
Randomization: The investigators will draw a set of birth dates - can then see who is in the intervention group in Beredt C19 (Norwegian emergency preparedness register for COVID-19) without identifying them individually (personal identification numbers are encrypted).
Primary outcome: Hospitalization or death caused by COVID-19 in a period of 10 weeks after invitations are sent.
Sample size calculations: 300 000 individuals in the intervention group, assuming risk of the primary outcome is at least 15% lower in the intervention group. (The investigators expect a large proportion NOT to accept the invitation to take the vaccine).
Detailed Description
Background and rationale
Several studies suggest a waning of COVID-19 vaccines' effectiveness over time, raising the question of whether booster doses should be offered to maintain protection against severe COVID-19.
Studies of the effectiveness of taking one booster dose, which for most people corresponds to a third vaccine dose, have shown promising results. Similarly, three recent studies examining the effectiveness of a 2nd booster dose found that the 2nd booster was associated with lower risk of severe COVID-19. All these studies are based on data from Israeli registries, comparing outcomes among individuals who have taken the booster, or not. Interpreting the findings from such non-experimental studies is challenging since there are likely systematic differences between those who accept the offer to take a booster dose, and those who do not. So called "healthy vaccinee bias" implies that those who take the vaccine are healthier than those not taking the vaccine. The opposite, however, may also be true: Those who perceive themselves to be more at risk may be more prone to accept the offer of vaccination. A related type of bias is the "premature efficacy bias" which is observed in many observational studies within one to two weeks after vaccination, probably due to people refraining from taking the vaccine if they suspect that they have already been infected. Comorbidities or socio-economic factors that are not adequately controlled for can also lead to biased results. The conventional approach to minimizing the risk of bias in effectiveness studies is to conduct a randomized trial - if feasible.
The future of the COVID-19 pandemic is unknown. In Norway, a large winter wave driven by the omicron variant of SARS-CoV-2 is receding after more than half the population has been infected. The vaccination coverage in the Norwegian population is also very high.
In the autumn of 2022, a new wave of infections may start due to waning immunity, and/or the emergence of a new variant.
Either way, vaccination will be the most important tool to reduce the risk of severe disease in individuals. Based on previous experiences and the available data, it is likely that health authorities in Norway (and probably other European countries) will offer or even recommend a 2nd booster dose (the fourth dose) to those who are aged 65 years and above. For those who are younger and therefore at lower risk of severe COVID-19, the value of a 2nd booster is less clear, making it difficult to decide for or against offering a 2nd booster to this group.
The investigators therefore propose to conduct a register-based randomized trial (RRCT) to provide evidence for the effects of offering a 2nd booster (a fourth dose) in the age group 45-64 years.
Objectives Our primary objective is to determine the effect of offering vaccination with a COVID-19 booster dose on severe COVID-19, measured by hospitalization and death caused by COVID-19.
Our secondary objective is to determine the effects (intended and unintended) of offering vaccination with a COVID-19 booster dose on the use of health care services, prescription medication related to COVID-19, and on SARS-CoV-2 infection rate.
Trial design The trial is designed as a register-based randomized trial. The investigators will draw a random sample from the whole population aged 45-64 years, which will constitute the intervention group and will receive a personal offer to receive a 2nd booster dose of a COVID-19 vaccine in their municipality. The rest of the population aged 45-64 will receive no such offer or information and will serve as control group. The random sample will be defined by drawing a set of birth dates. This allows the investigators to identify persons in the intervention group directly in the Norwegian Preparedness Register for COVID-19 without identifying them individually, since personal identification numbers are encrypted in this database. The random sample will receive the offer of vaccination either (i) via Helsenorge (National online health services in Norway) through a survey tool available to the Norwegian Institute of Public Health, or (ii) directly from their municipality (to be determined).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The trial is designed as a register-based randomized trial. The investigators will draw a random sample from the whole population aged 45-64 years, which will constitute the intervention group and will receive a personal offer to receive a 2nd booster dose of a COVID-19 vaccine in their municipality. The rest of the population aged 45-64 will receive no such offer or information and will serve as control group. The random sample will be defined by drawing a set of birth dates. This allows the investigators to identify persons in the intervention group directly in the Norwegian Preparedness Register for COVID-19 without identifying them individually, since personal identification numbers are encrypted in this database. The random sample will receive the offer of vaccination either (i) via Helsenorge (National online health services in Norway) , or (ii) directly from their municipality.
Masking
Outcomes Assessor
Masking Description
We will, to the extent feasible, mask the data analysts to group allocation.
Allocation
Randomized
Enrollment
600000 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention groups: Invitation to get 2nd booster
Arm Type
Experimental
Arm Description
Participants in the intervention group will receive an invitation to get a 2nd COVID-19 booster dose. Those who accept the invitation to be vaccinated will receive the vaccine through their municipality's vaccination service.
Arm Title
Control group: No invitation to get 2nd booster
Arm Type
No Intervention
Arm Description
The control group will receive no intervention.
Intervention Type
Other
Intervention Name(s)
Invitation to get a 2nd booster dose of COVID-19 vaccine
Intervention Description
Participants in the intervention group will receive an invitation to get a 2nd COVID-19 booster dose. Those who accept the invitation to be vaccinated will receive the vaccine through their municipality's vaccination service.
Primary Outcome Measure Information:
Title
Severe COVID-19
Description
Hospitalization or death caused by COVID-19 starting on day 22 after the invitation is sent to the intervention group.
Time Frame
To be decided, but no more the 3 months
Secondary Outcome Measure Information:
Title
Hospitalization or death
Description
Hospitalization or death from all causes
Time Frame
10 weeks
Title
Health care utilization
Description
Health care utilization and use of prescription medication related to COVID-19
Time Frame
10 weeks
Title
COVID-19 infection
Description
Registered COVID-19 infection
Time Frame
10 weeks
Title
Health care utilization related to potential side effects
Description
Health care utilization related to potential side effects of the COVID-19 vaccine (e.g., myocarditis)
Time Frame
10 weeks
Title
Infection, hospitalization or death
Description
Infection, hospitalization or death in a period of 12 months starting from the date of receiving the 1st booster dose
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Aged between 45 and 64 years
Registered in the Norwegian national population register
Have received three doses of a COVID-19 vaccine, with the last dose received at least four months ago.
Have not previously been offered or recommended a 4th dose for medical reasons
Exclusion Criteria:
Persons who have already been offered a 4th COVID-19 vaccine dose.
Persons in whom COVID-19 vaccination is contraindicated as per the vaccines' Summary of Product Characteristics (SPC).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Atle Fretheim, PhD MD
Phone
+4791649828
Email
atle.fretheim@fhi.no
First Name & Middle Initial & Last Name or Official Title & Degree
Cathinka H Julin, PhD
Phone
+4793882763
Email
cathinkahalle.julin@fhi.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Atle Fretheim, PhD MD
Organizational Affiliation
Norwegian Institute of Public Health
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We intend to give full access to the full protocol and statistical code, to anyone who is interested. We also intend to share anonymised IPD to the extent possible within the existing legal framework.
IPD Sharing Time Frame
We intend to make data available around six months after trial-start. The data will be available for at least 5-10 years.
IPD Sharing Access Criteria
No criteria - anyone who is interested will be given access.
Learn more about this trial
Trial of 2nd Booster Dose of COVID-19 Vaccine
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