The REnal Patients COVID-19 VACcination Immune Response (RECOVAC IR) Study

Covid19 Clinical Trial

— RECOVAC-IR  

Official title:

The Immune-response and Safety of COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant - A Prospective, Controlled, Multicenter Cohort Study by the RECOVAC Consortium

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04741386
• Other study ID #: NL76215.042.20
• Status: Completed
• Start date: February 17, 2021
• Est. completion date: February 25, 2022

Study information

• Verified date: March 2022
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Rationale: COVID-19 is associated with severely increased morbidity and mortality in patients with severely impaired kidney function, on dialysis or alive with a kidney transplant. Therefore, effective SARS-CoV-2 vaccination would be of great clinical importance in these patients. However, SARS-CoV-2 vaccination studies have excluded patients with chronic kidney disease (CKD) so-far.

Objective: To assess the efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages 4/5, on dialysis or alive with a kidney transplant as compared to controls.

Study design: prospective, controlled multicenter study Study population: 175 patients with CKD stages 4/5 (eGFR < 30 ml/min/1.73m2), 175 on dialysis , 300 alive with a kidney transplant and 200 controls (partners or sibblings of patients) Intervention: SARS-CoV-2 vaccination according to standard of care. Blood will be drawn at 4 different time points (baseline and at day 28, month 6 and in a subset 28 days after a third vaccination).

Main study parameters/endpoints: The primary endpoint is the antibody based immune response on day 28 after the second vaccination. Participants will be classified as responders or non-responders based on a spike (S)1 specific antibody levels of >=10 or <10 BAU/mL. The percentage of responders of each patient cohort will be compared with the percentage responders in the control group. Safety is a secondary endpoint which will be reported in terms of percentage of solicited local and systemic adverse events (AEs)graded according to severity. Other secondary endpoints include longevity of the immune response at 6 months, antibody respons 28 days after a third vaccination and levels of SARS-CoV-2 specific T and B cell responses.

Description:

OBJECTIVES

Primary objective:

To assess the antibody response after SARS-CoV-2 vaccination in patients with CKD stages 4/5, on dialysis or alive with a kidney transplant as compared to controls.

Secondary Objectives:

To assess in these groups of subjects after SARS-CoV 2 vaccination:

• durability of the antibody response

• the SARS-CoV-2-specific T and B cell response

• adverse events

• antibody response after third vaccination in patients on dialysis and kidney transplant recipients

Exploratory Objectives:

To assess in these groups of subjects after SARS-CoV 2 vaccination:

• the association between baseline (immune) parameters and the immune response to SARS-CoV-2 vaccination

• the neutralizing capacity of anti-COVID-19 antibodies

• the incidence of SARS-CoV-2 infection and outcome of COVID-19 disease during 6 months after SARS-CoV-2 vaccination and in a subset 28 days after third vaccination

STUDY DESIGN

This is a prospective, controlled multicenter cohort study to evaluate the efficacy and safety after SARS-CoV-2 vaccination in patients with CKD4/5, dialysis patients and kidney transplant recipients as compared to controls. Therefore, 4 cohorts will be included in this study.

• Cohort A: Patients with CKD stages 4 and 5 (eGFR <30 ml/min*1.73m2) (n = 175)

• Cohort B: Patients on hemodialysis and peritoneal dialysis (n = 175)

• Cohort C: Kidney Transplant Recipients (n= 300)

• Cohort D: Controls (n = 200)

Assessment of immune response:

Blood samples will be collected at baseline (i.e. prior to first vaccination) and 28 days, and 6 months after the second vaccination and in a subset 28 days after the third vaccination.

Evaluation other parameters:

To evaluate hematology parameters, liver and kidney function, additional blood samples will be collected at baseline, and 28 days and 6 months after the second vaccination.

Information on clinical course, incidence of SARS-CoV-2 infection, outcome of COVID-19 will be collected up to 6 months after second and in a subset 28 days after third vaccination for descriptive purposes.

METHODS

Main study parameter/endpoint:

The primary endpoint is the antibody based immune response to vaccination against COVID-19 on day 28 after the second vaccination as compared to controls.

Secondary study parameters/endpoints:

1. Duration and in-depth assessment of immune response through:

• Measurement of SARS-CoV2 specific antibodies at 6 months after vaccination to test the durability of response

• Assessment of SARS-CoV2 specific T and B cell response, 28 days, and 6 months after the second vaccination using a high throughput Interferon ɣ, IL-21 SARSCoV-2 specific T cell ELISPOT and SARS-CoV2 specific B cell memory ELISPOT.

2. Safety assessment through:

• Incidence and severity of solicited AEs during 7 days after each vaccination

3. Antibody based immune response after third vaccination:

• Measurement of SARS-CoV-2 specific antibodies at 28 days after third vaccination in patients on dialysis and kidney transplantation recipients.

Exploratory study parameters:

• Baseline (immune) parameters associated with vaccination response

• Neutralizing capacity of antibodies to test functionality

• In-depth flow-cytometric analyses for functional and phenotypical characterization of SARS-CoV-2 specific T cell responses will be performed followed by assessment of proliferative capacity, cytokine production and phenotypical markers in a subset of patients.

• Information on incidence of SARS-CoV-2 infection and outcome of COVID-19 disease during 6 months after second vaccination and in a subset 28 days after third vaccination will be collected.

• In a substudy in Radboudumc nasal strips will be collected and mucosal antibody response to COVID-19 analysed

Recruitment information / eligibility

• Status: Completed
• Enrollment: 854
• Est. completion date: February 25, 2022
• Est. primary completion date: June 4, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. All patients should be eligible for COVID-19 vaccination as described by the instructions of the manufacturer.

2. Age of 18 years or older

3. Capable of understanding the purpose and risks of the study, fully informed and given written informed consent

4. Either

• CKD4/5, with an eGFR <30 ml/min*1.73m2 by CKD-EPI

• Hemodialysis, or peritoneal dialysis

• KT recipient at least 6 weeks after transplantation

• Partner, sibling or family member of participating patient

Exclusion Criteria:

• 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)

• Multi-organ transplant recipients

• Previous or active COVID-19 disease

• Pregnancy or breastfeeding

• Active (haematological) malignancy

• Inherited immune deficiency

• Infection with Human Immunodeficiency Virus (HIV)

• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

Additional exclusion criterion for patients with CKD stages 4/5, on dialysis and controls:

• Individuals who receive maintenance treatment with immunosuppressive therapy in the 6 months before inclusion, including cytotoxic agents or systemic corticosteroids.

Additional exclusion criterion for controls:

• severely impaired kidney function, with an eGFR < 45 ml/min*1.73m2 by CKD-EPI

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• COVID-19
• Covid19
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Biological:
• SARS-CoV-2 vaccination
All participants will receive two vaccinations against COVID-19 according to the manufacturer's instructions.

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Center	Amsterdam	Noord-Holland
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Radboud university medical center	Nijmegen	Gelderland
Netherlands	Erasmus Medical Center	Rotterdam	Zuid-Holland

Sponsors (4)

Lead Sponsor	Collaborator
University Medical Center Groningen	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (11)

Ahn C, Amer H, Anglicheau D, Ascher NL, Baan CC, Battsetset G, Bat-Ireedui B, Berney T, Betjes MGH, Bichu S, Birn H, Brennan D, Bromberg J, Caillard S, Cannon RM, Cantarovich M, Chan A, Chen ZS, Chapman JR, Cole EH, Cross N, Durand F, Egawa H, Emond JC, Farrero M, Friend PJ, Geissler EK, Ha J, Haberal MA, Henderson ML, Hesselink DA, Humar A, Jassem W, Jeong JC, Kaplan B, Kee T, Kim SJ, Kumar D, Legendre CM, Man K, Moulin B, Muller E, Munkhbat R, Od-Erdene L, Perrin P, Rela M, Tanabe K, Tedesco Silva H, Tinckam KT, Tullius SG, Wong G. Global Transplantation COVID Report March 2020. Transplantation. 2020 Oct;104(10):1974-1983. doi: 10.1097/TP.0000000000003258. — View Citation

Gansevoort RT, Hilbrands LB. CKD is a key risk factor for COVID-19 mortality. Nat Rev Nephrol. 2020 Dec;16(12):705-706. doi: 10.1038/s41581-020-00349-4. — View Citation

Gezondheidsraad. Strategieën voor COVID-19-vaccinatie. Den Haag: Gezondheidsraad, 2020; publicatienr. 2020/23

Hilbrands LB, Duivenvoorden R, Vart P, Franssen CFM, Hemmelder MH, Jager KJ, Kieneker LM, Noordzij M, Pena MJ, Vries H, Arroyo D, Covic A, Crespo M, Goffin E, Islam M, Massy ZA, Montero N, Oliveira JP, Roca Muñoz A, Sanchez JE, Sridharan S, Winzeler R, Gansevoort RT; ERACODA Collaborators. COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration. Nephrol Dial Transplant. 2020 Nov 1;35(11):1973-1983. doi: 10.1093/ndt/gfaa261. Erratum in: Nephrol Dial Transplant. 2021 Feb 24;:. — View Citation

Hodgson SH, Mansatta K, Mallett G, Harris V, Emary KRW, Pollard AJ. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2. Lancet Infect Dis. 2021 Feb;21(2):e26-e35. doi: 10.1016/S1473-3099(20)30773-8. Epub 2020 Oct 27. Review. — View Citation

Katerinis I, Hadaya K, Duquesnoy R, Ferrari-Lacraz S, Meier S, van Delden C, Martin PY, Siegrist CA, Villard J. De novo anti-HLA antibody after pandemic H1N1 and seasonal influenza immunization in kidney transplant recipients. Am J Transplant. 2011 Aug;11(8):1727-33. doi: 10.1111/j.1600-6143.2011.03604.x. Epub 2011 Jun 14. — View Citation

Kotton CN. Immunization after kidney transplantation-what is necessary and what is safe? Nat Rev Nephrol. 2014 Oct;10(10):555-62. doi: 10.1038/nrneph.2014.122. Epub 2014 Jul 29. Review. — View Citation

Mahase E. Covid-19: Vaccine candidate may be more than 90% effective, interim results indicate. BMJ. 2020 Nov 9;371:m4347. doi: 10.1136/bmj.m4347. — View Citation

Reddy S, Chitturi C, Yee J. Vaccination in Chronic Kidney Disease. Adv Chronic Kidney Dis. 2019 Jan;26(1):72-78. doi: 10.1053/j.ackd.2018.10.002. Review. — View Citation

van Besouw NM, Yan L, de Kuiper R, Klepper M, Reijerkerk D, Dieterich M, Roelen DL, Claas FHJ, Clahsen-van Groningen MC, Hesselink DA, Baan CC. The Number of Donor-Specific IL-21 Producing Cells Before and After Transplantation Predicts Kidney Graft Rejection. Front Immunol. 2019 Apr 9;10:748. doi: 10.3389/fimmu.2019.00748. eCollection 2019. — View Citation

Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, Curtis HJ, Mehrkar A, Evans D, Inglesby P, Cockburn J, McDonald HI, MacKenna B, Tomlinson L, Douglas IJ, Rentsch CT, Mathur R, Wong AYS, Grieve R, Harrison D, Forbes H, Schultze A, Croker R, Parry J, Hester F, Harper S, Perera R, Evans SJW, Smeeth L, Goldacre B. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020 Aug;584(7821):430-436. doi: 10.1038/s41586-020-2521-4. Epub 2020 Jul 8. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The antibody based immune response to vaccination against COVID-19 as compared to controls	Participants will be classified as responders or non-responders based on seroconversion with a threshold for seropositivity based on Receiver Operator Curve (ROC) analysis and set at 10 BAU/mL in individuals without measurable anti-S antibodies at baseline.	28 days after the second vaccination
Secondary	Longevity of the antibody based immune response	Decline in antibodies and change in antibody response (defined as an antibody concentration above or below 10 BAU/mL)	6 months after the second vaccination
Secondary	SARS-CoV2 specific T and B cell response	using a high throughput Interferon ?, IL-21 SARSCoV-2 specific T cell ELISPOT and SARS-CoV2 specific B cell memory ELISPOT	28 days and 6 months after the second vaccination
Secondary	Incidence and severity of solicited adverse events	Using questionaires	during 7 days after each vaccination
Secondary	SARS CoV-2 spike-1 specific IgG antibody response after third COVID-19 vaccination	5 drops of blood will be drawn by home finger-prick blood test in a subset of patients	28 days after the third vaccination