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Trial registered on ANZCTR


Registration number
ACTRN12622001106729
Ethics application status
Approved
Date submitted
9/03/2022
Date registered
10/08/2022
Date last updated
10/08/2022
Date data sharing statement initially provided
10/08/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Safety and efficacy of the 3rd and the 4th dose of mRNA COVID19 vaccine in kidney transplant recipients
Scientific title
Safety and efficacy of the 3rd and the 4th dose of mRNA COVID19 vaccine in kidney transplant recipients
Secondary ID [1] 306647 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID19 vaccination response 325578 0
Kidney transplant recipients 325579 0
Condition category
Condition code
Infection 322946 322946 0 0
Studies of infection and infectious agents
Respiratory 324117 324117 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The participants undergo a two-step randomization process, each step forming two subgroups in 1:1 ratio, with the use of random block sizes of 4. The first step of randomization determines whether the patient receives 1 or 2 COVID19 vaccine booster doses (i.e., a total of 3 or 4 doses of vaccine 4 weeks apart of either BNT162b2 and mRNA-1273 vaccines), and the second step will determine which mRNA vaccine (either mRNA-1273, Moderna or BNT162b2, Pfizer/BioNTech) will be used (for 1 or both booster doses, respectively).
The vaccines were administered via intramuscular injection at transplant centre outpatient clinic. All patients attended a check-up visit a month after intervention to assess and monitor adverse events and effectivity of the intervention (see also later).
Intervention code [1] 323089 0
Treatment: Drugs
Intervention code [2] 323969 0
Prevention
Comparator / control treatment
The participants undergo a two-step randomization process, each step forming two subgroups in 1:1 ratio, with the use of random block sizes of 4. The first step of randomization determines whether the patient receives 1 (comparator group) or 2 (intervention group) COVID19 vaccine booster doses (i.e., a total of 3 or 4 doses of vaccine 4 weeks apart of either BNT162b2 and mRNA-1273 vaccines), and the second step will determine which mRNA vaccine (either mRNA-1273, Moderna or BNT162b2, Pfizer/BioNTech) will be used (for 1 or both booster doses, respectively).
Control group
Active

Outcomes
Primary outcome [1] 330715 0
positive humoral response (>10 AU/mL of SARS-CoV-2 IgG) of COVID19 mRNA vaccine.
- serum assay is performed a month after vaccination schedule is completed
Timepoint [1] 330715 0
at 1 month after final booster dose (3 versus 4 doses)
Secondary outcome [1] 407288 0
Comparison of humoral and cellular response to mRNA-1273, Moderna and BNT162b2, Pfizer/BioNTech for booster vaccine.
Comparison of adverse events between groups - assessed using a questionnaire designed for the stud; including occurrence of rejection (laboratory data assessment), de novo DSA formation, renal function evolvement.
Timepoint [1] 407288 0
at 1 month after each booster dose (3 resp. 4 doses)
Secondary outcome [2] 407289 0
Comparison of the efficacy of 3 versus 4 doses of COVID19 mRNA vaccine - evaluated using cellular immunity assessment. (EliSPOT assay - blood samples analysis)
Timepoint [2] 407289 0
at 1 month after final booster dose (3 versus 4 doses)
Secondary outcome [3] 407290 0
Incidence of COVID-19. (data-linkage to medical records)
Timepoint [3] 407290 0
At 3 months after final booster dose
Secondary outcome [4] 407291 0
Safety of booster vaccination and evaluation of adverse events (assessed using a questionnaire designed for the study) including occurrence of rejection (laboratory data assessment), de novo DSA formation, renal function evolvement.
Timepoint [4] 407291 0
at 1 month after each booster dose (3 resp. 4 doses)

Eligibility
Key inclusion criteria
- Adult (>18 years with no upper age limit) renal transplant (deceased or living donor) recipients, male or female.
- SARS-CoV-2 naive prior standard 2-dose vaccination and before booster doses
- Completed standard vaccination schedule with BNT162b2, Pfizer/BioNTech
- SARS-CoV-2 specific IgG antibody titer < 10 arbitrary units per milliliter (AU/mL)
- Ability to sign informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Confirmed active (RT-PCR) SARS-CoV-2 infection throughout the study
- Known previous SARS-CoV-2 infection
- SARS-CoV-2 specific IgG antibody titer greatrer than 10 arbitrary units per milliliter (AU/mL) upon enrollment
- Inability to complete full booster vaccination schedule (allergy, infection, etc.).
- Signs of active infection in baseline
- Inability to sign informed consent.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
random block sizes of 4 (permuted block randomisation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
24/09/2021
Date of last participant enrolment
Anticipated
Actual
1/10/2021
Date of last data collection
Anticipated
Actual
31/01/2022
Sample size
Target
140
Accrual to date
Final
126
Recruitment outside Australia
Country [1] 24651 0
Czech Republic
State/province [1] 24651 0

Funding & Sponsors
Funding source category [1] 310972 0
Government body
Name [1] 310972 0
Fighting INfectious Diseases "FIND"; Ministry of Education, Youth and Sports of the Czech Republic
Country [1] 310972 0
Czech Republic
Funding source category [2] 310975 0
University
Name [2] 310975 0
Cooperatio; Charles University in Prague
Country [2] 310975 0
Czech Republic
Primary sponsor type
Individual
Name
Martin Kacer
Address
University Hospital in Pilsen, Faculty of medicine in Pilsen, Charles University in Prague
alej Svobody 80
304 60 Pilsen
Czech Republic
Country
Czech Republic
Secondary sponsor category [1] 312282 0
University
Name [1] 312282 0
Faculty of Medicine in Pilsen, Charles Univeristy in Prague
Address [1] 312282 0
Husova 3
Pilsen 300 01
Czech Republic
Country [1] 312282 0
Czech Republic

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310531 0
Ethic committee of The University Hospital adn the Faculty of Medicine in Pilsen, Charles University in Prague
Ethics committee address [1] 310531 0
E.Benese 13, Pilsen, 30100
Ethics committee country [1] 310531 0
Czech Republic
Date submitted for ethics approval [1] 310531 0
26/08/2021
Approval date [1] 310531 0
02/09/2021
Ethics approval number [1] 310531 0
355/2021

Summary
Brief summary
The study will enroll 140 kidney transplant recipients eligible for the study. All participants will have previously (winter and spring 2021) received a complete standard 2-dose vaccination schedule from Pfizer/BioNTech (or Moderna). Once enrolled in the study, participants will undergo a two-step randomization process, each step forming two subgroups in 1:1 ratio, with the use of random block sizes of 4. The first step of randomization determines whether the patient receives 1 or 2 booster doses (i.e., a total of 3 or 4 doses of vaccine 4 weeks apart of either BNT162b2 and mRNA-1273 vaccines), and the second step will determine which mRNA vaccine (either mRNA-1273, Moderna or BNT162b2, Pfizer/BioNTech) will be used (for 1 or both booster doses, respectively). The transplant nephrologist will be responsible for the randomization process. Sealed, sequentially numbered envelopes will be used to conceal the allocation to groups. The study will not be further masked.
Immune response to vaccination will be measured at the baseline and 1 month after booster dose administration. Humoral response will be evaluated by measurement of SARS-CoV-2 specific IgG antibody titer. COVID19-specific cellular response will be investigated using an IFN-? ELISPOT performed on cryopreserved peripheral blood mononuclear cells using SARS-CoV-2 peptide pool as a stimulator. Alongside, relevant clinical data - especially adverse events attributable to vaccination, clinical efficacy of booster vaccination (occurrence of SARS-CoV-2 infection and its severity) – will be collected prospectively. A comparison of baseline and post-booster-dose COVID19-specific cellular and humoral response will be performed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117978 0
Dr Martin Kacer
Address 117978 0
University Hospital in Pilsen
alej Svobody 80, Pilsen. 30480
Country 117978 0
Czech Republic
Phone 117978 0
+420731487255
Fax 117978 0
Email 117978 0
[email protected]
Contact person for public queries
Name 117979 0
Martin Kacer
Address 117979 0
University Hospital in Pilsen, alej Svobody 80, Pilsen, 30480
Country 117979 0
Czech Republic
Phone 117979 0
+420731487255
Fax 117979 0
Email 117979 0
[email protected]
Contact person for scientific queries
Name 117980 0
Martin Kacer
Address 117980 0
University Hospital in Pilsen, alej Svobody 80, Pilsen, 30480
Country 117980 0
Czech Republic
Phone 117980 0
+420731487255
Fax 117980 0
Email 117980 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15362Study protocol  [email protected]
15364Ethical approval  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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