LESS CoV-2: RECOVAC - Long Term Efficacy and Safety of COVID-19 (SARS-CoV-2) Vaccination in Kidney Disease Patients
Study Details
Study Description
Brief Summary
Rationale: COVID-19 is associated with severely increased morbidity and mortality in patients with chronic kidney disease stage G4-G5 and patients on dialysis or after kidney transplantation. Therefore, effective SARS-CoV-2 vaccination would be of great clinical importance in these patients. However, SARS-CoV-2 vaccination studies have excluded these patients so-far. Literature data indicate that vaccination may be less effective in these patient groups.
Objective: To assess the efficacy and safety of SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, patients on dialysis or after kidney transplantation during two years follow-up after vaccination.
Study design: prospective single center observational cohort study.
Study population:
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all Dutch patients on dialysis with data registered in the Dutch Dialysis registry (RENINE)
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all Dutch patients after kidney transplantation with data registered in the Dutch national kidney transplant registry (NOTR).
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All Dutch patients with chronic kidney disease stage G4-G5 registered in the Santeon hospitals.
Intervention: After SARS-CoV-2 vaccination according to standard of care, blood will be drawn for antibody response measurements at day 28 and month 6 after 2nd vaccination at by mailer-based finger-prick in 3400 hemodialysis patients, 600 peritoneal dialysis patients, 4000 patients after kidney transplantation and 4000 patients with chronic kidney disease stage G4-G5. Patients who will undergo a 3rd SARS-CoV-2 vaccination via the national vaccination program for immunocompromised patients will be asked to carry out the mailer-based finger-prick 28 days after the 3rd SARS-CoV-2 vaccination, instead of the antibody measurement 6 months after the 2nd SARS-CoV-2 vaccination.
Main study parameters/endpoints:
The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as:
- the incidence of COVID-19 after vaccination.
Secondary endpoints are
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mortality
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adverse events of specific interest according to (inter)national authorities in collaboration with LAREB
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presence of HLA-antibodies in dialysis patients on the waiting list for a first kidney transplantation
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acute rejection and graft failure in patients after kidney transplantation In a subset of patients additional secondary endpoints will be assessed
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the antibody based immune response at 28 days after completion of SARS-CoV-2 vaccination.
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the durability of antibody based immune response at 6 months compared to at 28 days after having received two subsequent SARS-CoV-2 vaccinations, in patients that have not received a 3rd SARS-CoV-2 vaccine.
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the antibody based immune response at 28 days after having received the 3rd SARS-CoV-2 vaccination.
The incidence of these endpoints will be compared, if applicable, to those:
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in the general population who are vaccinated
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in patients on dialysis or after kidney transplant who are not vaccinated Within these patient groups endpoints will be compared between recipients of different vaccines.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
- OBJECTIVES
Primary objective:
To assess the efficacy of SARS-CoV-2 vaccination by the incidence of COVID-19 in patients with chronic kidney disease stage G4-G5, on dialysis and patients after kidney transplantation who received SARS-CoV-2 vaccination
Secondary Objectives:
- To assess the safety of vaccination
In a subgroup of participants:
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To assess the level of antibody response at 28 days and 6 months after SARS-CoV-2 vaccination
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To assess durability of the antibody response at 6 months after having received two subsequent SARS-CoV-2 vaccinations, in a subset of patients that have not received a 3rd SARS-CoV-2 vaccine
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the antibody based immune response at 28 days after having received the 3rd SARS-CoV-2 vaccination.
Exploratory Objectives:
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The vaccination coverage rate
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The severity of COVID-19 in case of infection
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The influence of vaccination on health-related quality of life by patient reported outcome measures (PROMs) in patients on dialysis.
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The SARS-CoV-2 genotype in patients with COVID-19
In a subgroup of participants:
- To assess the level of antibody response after vaccination between patients with
COVID-19 and without COVID-19 at:
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28 days after the 2nd SARS-CoV-2 vaccination
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28 days after the 3rd SARS-CoV-2 vaccination
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6 months after the 2nd SARS-CoV-2 vaccination in patients who have not received a 3rd vaccine.
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To assess change in behaviour towards measures against COVID-19 before and after vaccination
If data are available and applicable, outcomes in vaccinated patients on dialysis or after kidney transplantation will be compared:
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with outcomes in the general population
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with outcomes in patients with severely impaired kidney function (CKD stages G4/5), on dialysis or with a kidney transplant who are not vaccinated.
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according to the type of vaccination they received
- STUDY DESIGN
This is a prospective observational registry-based cohort study to evaluate the long-term efficacy and safety after SARS-CoV-2 vaccination on clinically important outcomes in patients with chronic kidney disease stage G4-G5, on dialysis or after kidney transplantation.
All participants will receive vaccination against COVID-19 via the national vaccination program and according to the manufacturer's instructions. To assess the immune response after vaccination, blood samples will be collected at 28 days after the 2nd SARS-CoV-2 vaccination, 28 days after the 3rd SARS-CoV-2 vaccination, and 6 months after the 2nd SARS-CoV-2 vaccination in patients who have not received a 3rd vaccination. In total a maximum of 1 ml blood will be drawn.
Data of the following cohorts will be analyzed in this study.
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Patiens with chronic kidney disease stage G4-G5, data to be derived from the Santeon hospitals.
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Patients on hemodialysis and peritoneal dialysis, data to be derived from the existing national registry RENINE
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Kidney transplant recipients, data to be derived from the existing national registry NOTR
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Patients on dialysis or after kidney transplantation with COVID-19 disease, data to be derived from the ERACODA database.
- METHODS
Main study parameter/endpoint:
The primary endpoints is the incidence of COVID-19 in a two years period after SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, on dialysis or after kidney transplantation.
Secondary study parameters/endpoints:
Safety in all patients:
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Incidence of mortality
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Incidence of adverse events of specific interest as defined by (inter)national authorities in collaboration with LAREB
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Incidence of a combined endpoint of acute rejection or graft failure in patients after kidney transplantation
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Incidence of HLA antibodies defined as calculated Panel Reactivity Antibodies (cPRA) > 5% in patients on the waiting list for their first kidney transplantation
Efficacy in a subgroup of patients:
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The antibody response against the SARS-CoV-2 Receptor Binding Domain at 28 days after the final SARS-CoV-2 vaccination.
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The antibody response against the SARS-CoV-2 Receptor Binding Domain at 28 days after the 3rd SARS-CoV-2 vaccination.
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The durability of antibody based immune response against SARS-CoV-2 Receptor Binding Domain at 6 months compared to 28 days after completion of SARS-CoV-2 vaccination in patients who did not receive a 3rd SARS-CoV-2 vaccination.
Exploratory study parameters:
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Vaccination coverage rates
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Disease severity in patients who develop COVID-19, assessed as
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Hospitalization
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ICU admission
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Mechanical ventilation
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Mortality
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The influence of vaccination on health-related quality of life by patient reported outcome measures (PROMs) in dialysis patients
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SARS-CoV-2 genotype in patients with COVID-19
In a subgroup of participants:
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To assess the level of SARS-CoV-2 Receptor Binding Domain antibody response after vaccination between patients with COVID-19 and without COVID-19 at:
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28 days after the 2nd SARS-CoV-2 vaccination
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28 days after the 3rd SARS-CoV-2 vaccination
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6 months after the 2nd SARS-CoV-2 vaccination in patients who have not received a 3rd vaccine.
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To assess change in behaviour towards measures against COVID-19 before and after vaccination
These data collected after SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, on dialysis and after a kidney transplantation will (if applicable data are available) be compared:
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to those obtained in the general population
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to those obtained in patients with chronic kidney disease stage G4-G5, on dialysis or with a kidney transplant who are not vaccinated
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according to the type of vaccination received These comparisons will allow us to analyze whether SARS-CoV-2 vaccination offers efficacy to prevent COVID-19 and sufficient safety in patients with chronic kidney disease stage G4-G5, dialysis and kidney transplant patients when compared to non-vaccinated patients with chronic kidney disease stage G4-G5, dialysis and kidney transplant patients, whether the efficacy is similar as in the general population, and whether there are differences in the risk-benefit ratio between the various vaccines.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| CKD4/5 Patients with chronic kidney disease stage G4-G5 without dialysis or with a kidney transplant |
Diagnostic Test: mailer-based finger-prick
All participants in the antibody measurement study will be sent a mailer-based finger-prick set. The sets will be sent to the home address of the patient, including a return envelope. After collecting and returning the samples SARS-CoV-2 antibodies will be analysed quantitatively at the laboratory.
Other Names:
|
| Dialysis Patients on hemodialysis and peritoneal dialysis |
Diagnostic Test: mailer-based finger-prick
All participants in the antibody measurement study will be sent a mailer-based finger-prick set. The sets will be sent to the home address of the patient, including a return envelope. After collecting and returning the samples SARS-CoV-2 antibodies will be analysed quantitatively at the laboratory.
Other Names:
|
| Kidney transplant Patients with a kidney transplant at least 6 weeks after transplantation |
Diagnostic Test: mailer-based finger-prick
All participants in the antibody measurement study will be sent a mailer-based finger-prick set. The sets will be sent to the home address of the patient, including a return envelope. After collecting and returning the samples SARS-CoV-2 antibodies will be analysed quantitatively at the laboratory.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The incidence of COVID-19 [two years after SARS-CoV-2 vaccination]
After SARS-CoV-2 vaccination in patients with chronic kidney disease stage G4-G5, on dialysis or after kidney transplantation.
Secondary Outcome Measures
- Incidence of mortality [two years after SARS-CoV-2 vaccination]
Incidence of mortality in patients with chronic kidney disease stage G4-G5, on dialysis or after kidney transplantation.
- Incidence of adverse events [two years after SARS-CoV-2 vaccination]
Incidence of adverse events of specific interest as defined by (inter)national authorities in collaboration with LAREB
- Incidence of acute rejection or graft failure in kidney transplant recipients [two years after SARS-CoV-2 vaccination]
Incidence of a combined endpoint of acute rejection or graft failure in patients after kidney transplantation
- Incidence of HLA antibodies measured in blood [two years after SARS-CoV-2 vaccination]
Incidence of HLA antibodies defined as calculated Panel Reactivity Antibodies (cPRA) > 5% in patients on the waiting list for their first kidney transplantation
- The antibody level against the SARS-CoV-2 Receptor Binding Domain measured in blood [28 days after second SARS-CoV-2 vaccination.]
The antibody response against the SARS-CoV-2 Receptor Binding Domain
- The antibody level against SARS-CoV-2 Receptor Binding Domain measured in blood [6 months after second SARS-CoV-2 vaccination]
The antibody based immune response against SARS-CoV-2 Receptor Binding Domain at 6 months compared to 28 days after completion of SARS-CoV-2 vaccination in patients without a third vaccination.
- The antibody level against SARS-CoV-2 Receptor Binding Domain measured in blood [28 days after third SARS-CoV-2 vaccination]
The antibody based immune response against SARS-CoV-2 Receptor Binding Domain at 28 days after a third vaccination
Other Outcome Measures
- Vaccination coverage rate [two years]
Percentage of patients vaccinated
- SARS-CoV-2 genotype [two years]
In patients with active COVID-19 infection
- Level of SARS-CoV-2 Receptor Binding Domain antibody in patients with and without COVID-19 [two years]
level of SARS-CoV-2 Receptor Binding Domain antibody response at 28 days and 6 months after the second SARS-CoV-2 vaccination (in patients who did not receive a third vaccination) or 28 days after the third SARS-CoV-2 vaccination between patients who develop COVID-19 and who do not develop COVID-19 after vaccination
- Disease severity of COVID-19 in case of infection assessed by ICU admission [two years]
Number of ICU admissions with COVID-19 after vaccination
- Disease severity of COVID-19 in case of infection assessed by mechanical ventilation [two years]
Number of cases with mechanical ventilation because of COVID-19 after vaccination
- Disease severity of COVID-19 in case of infection assessed by mortality [two years]
Number of deaths due to COVID-19 after vaccination
- Disease severity of COVID-19 in case of infection assessed by hospitalization [two years]
Number of hospital admissions with COVID-19 infection after vaccination
- Influence of vaccination on health related quality of life - SF-12 [two years]
Measured by Patient Reported Outcome Measures (PROMs). This is a questionnaire consisting of two parts. The first part includes the 12 items Short Form (SF-12) health survey to monitor physical and mental quality of life (with a score on 8 categories ranging from 0-100; with a higher score defined as a higher quality of life). Scores before and after vaccination will be compared.
- Influence of vaccination on health related quality of life - DSI [two years]
Measured by Patient Reported Outcome Measures (PROMs). This is a questionnaire consisting of two parts. The second part includes the Dialysis Symptom Index (DSI) questionnaire to monitor disease specific burden from the perspective of patients (with a score ranging from 0-30, with a higher score defined as a higher disease burden). Scores before and after vaccination will be compared.
- Change in behaviour towards measures against COVID-19 [two years]
Estimated by questionnaires, created by the studyteam in collaboration with the Dutch patient association. This questionnaire is focused on mental aspect of COVID-19 measures and whether certain measures, results or extra vaccinations influence behaviour of patients
Eligibility Criteria
Criteria
Inclusion Criteria:
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Eligible for COVID-19 vaccination as described by the instructions of the manufacturer.
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Age of 18 years or older
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Capable of understanding the purpose and risks of the study, fully informed and given written informed consent (signed informed consent form has been obtained)
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Either
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eGFR < 30 ml/min/1.73m2 but not on dialysis or with a kidney transplant
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Hemodialysis, or peritoneal dialysis
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Kidney Transplant recipient at least 6 weeks after transplantation
Exclusion Criteria:
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History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention(s).
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Patients who opted out for research in the Santeon, RENINE and NOTR registries.
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Patients who participate in the RECOVAC-IR study.
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Of note, patients will be eligible whether or not they have a history of COVID-19. Analyses will be performed in the overall population, but also shown separately for those without and with a history of COVID-19.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Medical Center Groningen | Groningen | Netherlands | 9713 GZ |
Sponsors and Collaborators
- University Medical Center Groningen
Investigators
- Study Director: Jan-Stephan F Sanders, MD PhD, University Medical Center Groningen
- Principal Investigator: Marc H Hemmelder, MD PhD, Maastricht University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL76839.042.21