SARS-CoV InfectionPhase 4ENFORCENCT04760132
National Cohort Study of Effectiveness and Safety of SARS-CoV-2/COVID-19 Vaccines (ENFORCE)
A Phase 4 study testing COMIRNATY - BioNTech Manufacturing GmbH, COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH and COVID-19 Vaccine AstraZeneca suspension for injection in people with SARS-CoV Infection, run by Jens D Lundgren, MD at 5 sites in Denmark.
Trial summary
National cohort study of effectiveness and safety of SARS-CoV-2 vaccines (ENFORCE is an equivalence trial to evaluate the effectiveness and safety of multiple new SARS-CoV-2 vaccines approved for use in the EU, and which are being offered at participating units. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- SARS-CoV Infection
- What is being tested?
- COMIRNATY - BioNTech Manufacturing GmbH, COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH and COVID-19 Vaccine AstraZeneca suspension for injection
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7,600 participants
- Where
- 5 sitesDenmark
- Study dates
- 8 Feb 2021to 31 Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent obtained before any trial related procedures are performed
- Male or female eligible for SARS-CoV-2 immunization (as defined by SST in the national vaccination plan)
- The subject must be willing and able to comply with trial protocol (re-visits and biological samples)
Who cannot join
- Male and female under the age of 18
- Any subgroup of individuals for which the vaccines are contraindicated
- Previous SARS-CoV-2 vaccination
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Denmark5 sites
Aalborg Universityhospital Syd
Aalborg, 9000
Aarhus Universitetshospital, Skejby
Aarhus, Aarhus N, 8200
Hvidovre Hospital
Hvidovre, 2600
Odense Universityhospital
Odense, 5000
Sjællandsuniversitetshospital
Roskilde, 4000
About this study
Official title: National Cohort Study of Effectiveness and Safety of SARS-CoV-2/COVID-19 Vaccines
National cohort study of effectiveness and safety of SARS-CoV-2 vaccines (ENFORCE is an equivalence trial to evaluate the effectiveness and safety of multiple new SARS-CoV-2 vaccines approved for use in the EU, and which are being offered at participating units.
The design is an open-labelled, non-randomised, parallel group, phase IV study with historical controls.
A sub-study will be embedded within this master protocol addressing basic and translational research questions requiring additional sampling of biological material (under separate participant informed consent).
Read the detailed description
First phase will enrol 10,000 persons initiating vaccination (assuming 4 vaccines). If more vaccines become available additional 2,500 persons per vaccine will be included. Subsequent phases with larger sections of the population included may be implemented.
Participants will have 6 study visits and be followed for 2 years after the first vaccination, which offers the participants an extra close follow up on vaccine effectiveness. Safety data will be collected at study visits until 3 months after the first vaccination. Research samples will be collected at each study visit during the two year follow-up
- Conditions
- SARS-CoV Infection
- Being tested
- COMIRNATY - BioNTech Manufacturing GmbH, COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH, COVID-19 Vaccine AstraZeneca suspension for injection
- Keywords
- COVID-19, Vaccination
- Medical subject headings
- Severe Acute Respiratory Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
COMIRNATY - BioNTech Manufacturing GmbHBiological
Vaccination as part of the the Danish national government programme
COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECHBiological
Vaccination as part of the the Danish national government programme
COVID-19 Vaccine AstraZeneca suspension for injectionBiological
Vaccination as part of the the Danish national government programme
| Study group | Role | What they receive |
|---|---|---|
| Vaccine A - COMIRNATY COVID-19 vaccine | Active comparator | COMIRNATY (COVID-19, mRNA Vaccine) by BioNTech Manufacturing GmbH Marketing Authorisation EU/1/20/1528 Receives: Biological: COMIRNATY - BioNTech Manufacturing GmbH |
| Vaccine B - Moderna COVID-19 vaccine | Active comparator | COVID-19 Vaccine Moderna dispersion for injection (COVID-19, mRNA Vaccine) by MODERNA BIOTECH SPAIN S.L.
Marketing Authorisation EU/1/20/1507/001 Receives: Biological: COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH |
| Vaccine C - Astra-Zeneca COVID-19 vaccine | Active comparator | COVID-19 Vaccine AstraZeneca suspension for injection (ChAdOx1-S [recombinant]) by AstraZeneca AB Marketing Authorisation EU/1/21/1529/001 and /002 Receives: Biological: COVID-19 Vaccine AstraZeneca suspension for injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the effectiveness of citizens being vaccinated with one of the SARS-CoV-2 vaccines
Primary outcome is the minimal protective neutralising antibody titre (MPNAT); i.e. the minimum level of neutralising antibodies sufficient to protect the person from becoming infected.
Measured: The change from Base-line in MPNAT measured via profiling of antibodies against SARS-CoV-2 Spike epitopes at 24 month
Secondary outcomes (3)
Number of breakthrough infections in the 24 months period will be used to compare the effectiveness between the vaccines
Number of confirmed positive SARS-CoV-2 tests reported via the national testing system.
Measured: The change from first vaccination until 24 month
Assessment of the safety of the vaccines will be compared between groups
Reports of participants with local and systemic reactions to the vaccination will be collected
Measured: From first vaccine until Day 90
Assessment of any Adverse Event from the vaccines will be compared between groups
Reports of participants with grade 3 and 4 Adverse Events and any Serious Adverse will be collected
Measured: From first vaccine until Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2021
- Study start8 Feb 2021
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The design is an open-labelled, non-randomised, parallel group, phase IV study with historical controls.
- Masking
- None (open label)
- Enrolment
- 7,600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jens D Lundgren, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of the Interior and Health, Denmark
- Responsible party
- Sponsor-investigator, Jens D Lundgren, MD, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Jens Lundgren, Professor, Study chair, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04760132
- Sponsor's protocol ID
- ENFORCE
- Acronym
- ENFORCE
- Status last verified
- Apr 2024
- First submitted
- 8 Feb 2021
- Last updated
- 12 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Staerke NB, Reekie J, Johansen IS, Nielsen H, Benfield T, Wiese L, Sogaard OS, Tolstrup M, Iversen KK, Tarp B, Larsen FD, Larsen L, Lindvig SO, Holden IK, Iversen MB, Knudsen LS, Fogh K, Jakobsen ML, Traytel AK, Ostergaard L, Lundgren J; ENFORCE Study Group. Cohort Profile:The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE). BMJ Open. 2022 Dec 30;12(12):e069065. doi: 10.1136/bmjopen-2022-069065.
PubMed 36585137
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- National Cohort Study of Effectiveness and Safety of SARS-CoV-2/COVID-19 Vaccines
- ClinicalTrials.gov ID
- NCT04760132
- Acronym / sponsor ID
- ENFORCE / ENFORCE
- Conditions
- SARS-CoV Infection
- Keywords
- COVID-19, Vaccination
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7,600 participants (actual)
- Lead sponsor
- Jens D Lundgren, MDUniversity, hospital or other
- Collaborators
- Ministry of the Interior and Health, Denmark
- Study start
- 8 Feb 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 18 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
National cohort study of effectiveness and safety of SARS-CoV-2 vaccines (ENFORCE is an equivalence trial to evaluate the effectiveness and safety of multiple new SARS-CoV-2 vaccines approved for use in the EU, and which are being offered at participating units.
The design is an open-labelled, non-randomised, parallel group, phase IV study with historical controls.
A sub-study will be embedded within this master protocol addressing basic and translational research questions requiring additional sampling of biological material (under separate participant informed consent).
Detailed description
First phase will enrol 10,000 persons initiating vaccination (assuming 4 vaccines). If more vaccines become available additional 2,500 persons per vaccine will be included. Subsequent phases with larger sections of the population included may be implemented.
Participants will have 6 study visits and be followed for 2 years after the first vaccination, which offers the participants an extra close follow up on vaccine effectiveness. Safety data will be collected at study visits until 3 months after the first vaccination. Research samples will be collected at each study visit during the two year follow-up
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The design is an open-labelled, non-randomised, parallel group, phase IV study with historical controls.
| Arm | Type | Receives |
|---|---|---|
| Vaccine A - COMIRNATY COVID-19 vaccine | Active comparator | Biological: COMIRNATY - BioNTech Manufacturing GmbHCOMIRNATY (COVID-19, mRNA Vaccine) by BioNTech Manufacturing GmbH Marketing Authorisation EU/1/20/1528 |
| Vaccine B - Moderna COVID-19 vaccine | Active comparator | Biological: COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECHCOVID-19 Vaccine Moderna dispersion for injection (COVID-19, mRNA Vaccine) by MODERNA BIOTECH SPAIN S.L. Marketing Authorisation EU/1/20/1507/001 |
| Vaccine C - Astra-Zeneca COVID-19 vaccine | Active comparator | Biological: COVID-19 Vaccine AstraZeneca suspension for injectionCOVID-19 Vaccine AstraZeneca suspension for injection (ChAdOx1-S [recombinant]) by AstraZeneca AB Marketing Authorisation EU/1/21/1529/001 and /002 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Written informed consent obtained before any trial related procedures are performed
- Male or female eligible for SARS-CoV-2 immunization (as defined by SST in the national vaccination plan)
- The subject must be willing and able to comply with trial protocol (re-visits and biological samples)
Key exclusion criteria (3 listed)
- Male and female under the age of 18
- Any subgroup of individuals for which the vaccines are contraindicated
- Previous SARS-CoV-2 vaccination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| COMIRNATY - BioNTech Manufacturing GmbHVaccination as part of the the Danish national government programme | Biological | Vaccine A - COMIRNATY COVID-19 vaccine |
| COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECHVaccination as part of the the Danish national government programme | Biological | Vaccine B - Moderna COVID-19 vaccine |
| COVID-19 Vaccine AstraZeneca suspension for injectionVaccination as part of the the Danish national government programme | Biological | Vaccine C - Astra-Zeneca COVID-19 vaccine |
Primary outcome
Assessment of the effectiveness of citizens being vaccinated with one of the SARS-CoV-2 vaccines
Time frame: The change from Base-line in MPNAT measured via profiling of antibodies against SARS-CoV-2 Spike epitopes at 24 month
Primary outcome is the minimal protective neutralising antibody titre (MPNAT); i.e. the minimum level of neutralising antibodies sufficient to protect the person from becoming infected.
3 secondary outcomes
Number of breakthrough infections in the 24 months period will be used to compare the effectiveness between the vaccines
Time frame: The change from first vaccination until 24 month
Assessment of the safety of the vaccines will be compared between groups
Time frame: From first vaccine until Day 90
Assessment of any Adverse Event from the vaccines will be compared between groups
Time frame: From first vaccine until Day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Derived from this study: PubMed 36585137Staerke NB, Reekie J, Johansen IS, Nielsen H, Benfield T, Wiese L, Sogaard OS, Tolstrup M, Iversen KK, Tarp B, Larsen FD, Larsen L, Lindvig SO, Holden IK, Iversen MB, Knudsen LS, Fogh K, Jakobsen ML, Traytel AK, Ostergaard L, Lundgren J; ENFORCE Study Group. Cohort Profile:The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE). BMJ Open. 2022 Dec 30;12(12):e069065. doi: 10.1136/bmjopen-2022-069065.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Lundgren, Professor study chair
Copenhagen University Hospital, Rigshospitalet
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing COMIRNATY - BioNTech Manufacturing GmbH, COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH and COVID-19 Vaccine AstraZeneca suspension for injection in people with SARS-CoV Infection, run by Jens D Lundgren, MD at 5 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the effectiveness of citizens being vaccinated with one of the SARS-CoV-2 vaccines (time frame: The change from Base-line in MPNAT measured via profiling of antibodies against SARS-CoV-2 Spike epitopes at 24 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04760132, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2024.