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

NCT04741386 | Completed DMC

• 1 other identifier: NL76215.042.20
• Study Type: observational
• Target: 854
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Covid19; Chronic Kidney Diseases

Keywords

SARS-CoV-2 vaccination; Antibody based immune response; SARS-CoV-2 specific T and B cell response

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Longevity of the antibody based immune response

  6 months after the second vaccination

• SARS-CoV2 specific T and B cell response

  28 days and 6 months after the second vaccination

• Incidence and severity of solicited adverse events

  during 7 days after each vaccination

• SARS CoV-2 spike-1 specific IgG antibody response after third COVID-19 vaccination

  28 days after the third vaccination

Study Arms (4)

Cohort A

Patients with CKD stages 4 and 5

Biological: SARS-CoV-2 vaccination

Cohort B

Patients on hemodialysis and peritoneal dialysis

Biological: SARS-CoV-2 vaccination

Cohort C

Kidney Transplant Recipients

Biological: SARS-CoV-2 vaccination

Cohort D

Controls

Biological: SARS-CoV-2 vaccination

Interventions

SARS-CoV-2 vaccination BIOLOGICAL

All participants will receive two vaccinations against COVID-19 according to the manufacturer's instructions.

Cohort A; Cohort B; Cohort C; Cohort D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* At all four participating centers (UMCG, ErasmusMC, Radboudumc and Amsterdam UMC) out-patient clinics with at least 100 patients with CKD4/5 are available for recruitment in this study. * At all three participating centers approximately 50-100 hemodialysis and peritoneal dialysis patients are being treated, from this population eligible patients will be included. * Kidney transplant recipients at UMCG, Erasmus MC, Radboudumc and Amsterdam UMC will be eligible. In each participating center 130 to 200 patients receive a kidney transplant yearly, and per center 1000-2000 kidney transplant recipients are under regular outpatient follow-up. * Partners, siblings or family members of participating patients will be asked as controls.

You may qualify if:

• All patients should be eligible for COVID-19 vaccination as described by the instructions of the manufacturer.
• Age of 18 years or older
• Capable of understanding the purpose and risks of the study, fully informed and given written informed consent
• 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

You may not qualify if:

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

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Erasmus Medical Center: collaborator
• Radboud University Medical Center: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (4)

Radboud university medical center

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Amsterdam University Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, 3015 GD, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Related Publications (14)

• 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. No abstract available.

  PMID: 32243281 BACKGROUND

• 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.

  PMID: 32848205 BACKGROUND

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

  BACKGROUND

• 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 Munoz 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.

  PMID: 33151337 BACKGROUND

• 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.

  PMID: 33125914 BACKGROUND

• 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.

  PMID: 21672157 BACKGROUND

• 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.

  PMID: 25072119 BACKGROUND

• 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. No abstract available.

  PMID: 33168562 BACKGROUND

• 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.

  PMID: 30876620 BACKGROUND

• 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.

  PMID: 31024571 BACKGROUND

• 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.

  PMID: 32640463 BACKGROUND

• Vervoort JPM, Konijn WS, Jansen DEMC, Boersma C, de Zeeuw J, Ho-Dac-Pannekeet MM, Gansevoort RT, Messchendorp AL, Sanders JSF, de Wildt-Liesveld R. Patient engagement as a collaborative process in a large Dutch COVID-19 vaccination study (RECOVAC) - insight into the contribution of patient engagement and learnings for the future. Res Involv Engagem. 2024 Sep 13;10(1):96. doi: 10.1186/s40900-024-00622-x.

  PMID: 39272117 DERIVED

• Sanders JF, Messchendorp AL, de Vries RD, Baan CC, van Baarle D, van Binnendijk R, Diavatopoulos DA, Geers D, Schmitz KS, GeurtsvanKessel CH, den Hartog G, Kho MML, Koopmans MPG, van der Molen RG, Remmerswaal EBM, Rots N, Gansevoort RT, Bemelman FJ, Hilbrands LB, Reinders MEJ; VACcination Immune Response Study (RECOVAC) Collaborators. Antibody and T-Cell Responses 6 Months After Coronavirus Disease 2019 Messenger RNA-1273 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant. Clin Infect Dis. 2023 Feb 8;76(3):e188-e199. doi: 10.1093/cid/ciac557.

  PMID: 35796536 DERIVED

• Sanders JF, Bemelman FJ, Messchendorp AL, Baan CC, van Baarle D, van Binnendijk R, Diavatopoulos DA, Frolke SC, Geers D, GeurtsvanKessel CH, den Hartog G, van der Heiden M, Imhof C, Kho MML, Koopmans MPG, Malahe SRK, Mattheussens WB, van der Molen R, van Mourik D, Remmerswaal EBM, Rots N, Vart P, de Vries RD, Gansevoort RT, Hilbrands LB, Reinders MEJ; RECOVAC Collaborators. The RECOVAC Immune-response Study: The Immunogenicity, Tolerability, and Safety of COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant. Transplantation. 2022 Apr 1;106(4):821-834. doi: 10.1097/TP.0000000000003983.

  PMID: 34753894 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

In total 3x50 ml heparin blood blood and 4x5 mL serum will be drawn and stored. In a subset of participants a total of 5 nasal strips will be collected and stored.

MeSH Terms

Conditions

COVID-19; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jan-Stephan F Sanders, MD PhD

  University Medical Center Groningen

  STUDY DIRECTOR

• Ron T Gansevoort, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Luuk B Hilbrands, MD PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Marlies EJ Reinders, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Frederike J Bemelman, MD PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 5, 2021
• Study Start: February 17, 2021
• Primary Completion: June 4, 2021
• Study Completion: February 25, 2022
• Last Updated: April 4, 2022

Record last verified: 2022-03

Locations

NL (4)