Medicine

BOOST KIDNEY - BOOST KIDNEY: A Multi-Centre 12 Month Parallel-Group Randomized Control Trial of BNT162b2 versus mRNA-1273 COVID-19 Vaccine Boosters in Chronic Kidney Disease and Dialysis Patients with Poor Humoral Response following COVID-19 Vaccination

Principal investigator
Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre

Summary
Chronic kidney disease (CKD) affects more than 10 per cent of Canadians. CKD patients, especially those receiving dialysis, are highly susceptible to infections, and SARS-CoV-2 infections in this group have been more severe than in the general population leading to frequent hospitalizations and higher mortality rates. Often, people with CKD have a weaker response to traditional vaccines so they may remain vulnerable to COVID-19.

BOOST KIDNEY is a parallel, randomized controlled trial aiming at studying whether third dose BNT162b2 or mRNA-1273 for the third dose results in differences in vaccine-induced immune responses. Participants are randomized to receive either BNT162b2 or mRNA-1273 as a third dose booster. Blood is collected at 1, 3, 6, 9 and 12 months post booster to measure the serologic response.

Sample size: 273 Chronic Kidney Disease and dialysis patients.

Intervention: BNT162b2 (Pfizer) and mRNA-1273 (Moderna) COVID-19 Vaccines.

ClinicalTrials.gov (NCT#)
NCT05022329

Trial email
COVID-CKD@sunnybrook.ca

Trial Locations
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Toronto General Hospital, Toronto, Ontario, Canada
Scarborough General Hospital, Scarborough, Ontario, Canada

COVID-CKD (Observational Study) - Determining the Safety and Efficacy of COVID-19 Vaccination in the Chronic Kidney Disease Population

Principal investigator
Dr. Matthew Oliver, Sunnybrook Health Sciences Centre
Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre
Dr. Adeera Levin, University of British Columbia

Summary

Chronic kidney disease (CKD) affects more than 10 per cent of Canadians. CKD patients, especially those receiving dialysis, are highly susceptible to infections, and SARS-CoV-2 infections in this group have been more severe than in the general population leading to frequent hospitalizations and higher mortality rates. Often, people with CKD have a weaker response to traditional vaccines so they may remain vulnerable to COVID-19.

This observational study aims to determine if COVID-19 vaccines generate adequate immune response in this population and how well the vaccines prevent COVID-19 infection.

Sample size: 2337

Intervention: None, observational

Primary Outcomes:
To determine the safety and serological response to COVID-19 vaccination, as well as potential booster shots, among individuals with CKD stages 3b, 4 and 5.

Trial email
COVID-CKD@sunnybrook.ca

Trial Locations
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Toronto General Hospital, Toronto, Ontario, Canada
St. Michael ‘s Hospital, Toronto, Ontario, Canada
Michael Garron Hospital, Toronto, Ontario, Canada
St. Paul‘s Hospital, Vancouver, British Columbia, Canada

Yau K, Abe KT, Naimark D, Oliver MJ, Perl J, Leis JA, Bolotin S, Tran V, Mullin SI, Shadowitz E, Gonzalez A, Sukovic T, Garnham-Takaoka J, de Launay KQ, Takaoka A, Straus SE, McGeer AJ, Chan CT, Colwill K, Gingras AC, Hladunewich MA. Evaluation of the SARS-CoV-2 Antibody Response to the BNT162b2 Vaccine in Patients Undergoing Hemodialysis. JAMA Netw Open. 2021 Sep 1;4(9):e2123622. doi: 10.1001/jamanetworkopen.2021.23622. PMID: 34473256; PMCID: PMC8414193. https://pubmed.ncbi.nlm.nih.gov/34473256/

Oliver MJ, Thomas D, Balamchi S, Ip J, Naylor K, Dixon SN, McArthur E, Kwong J, Perl J, Atiquzzaman M, Singer J, Yeung A, Hladunewich M, Yau K, Garg AX, Leis JA, Levin A, Krajden M, Blake PG. Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada. J Am Soc Nephrol. 2022 Apr;33(4):839-849. doi: 10.1681/ASN.2021091262. Epub 2022 Mar 9. PMID: 35264455; PMCID: PMC8970446. https://pubmed.ncbi.nlm.nih.gov/35264455/

Oliver MJ, Blake PG. Clinical Utility of COVID-19 Vaccination in Patients Undergoing Hemodialysis. Clin J Am Soc Nephrol. 2022 Jun;17(6):779-781. doi: 10.2215/CJN.04930422. PMID: 35649720; PMCID: PMC9269653. https://pubmed.ncbi.nlm.nih.gov/35649720/

Colwill K, Galipeau Y, Stuible M, Gervais C, Arnold C, Rathod B, Abe KT, Wang JH, Pasculescu A, Maltseva M, Rocheleau L, Pelchat M, Fazel-Zarandi M, Iskilova M, Barrios-Rodiles M, Bennett L, Yau K, Cholette F, Mesa C, Li AX, Paterson A, Hladunewich MA, Goodwin PJ, Wrana JL, Drews SJ, Mubareka S, McGeer AJ, Kim J, Langlois MA, Gingras AC, Durocher Y. A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination. Clin Transl Immunology. 2022 Mar 23;11(3):e1380. doi: 10.1002/cti2.1380. PMID: 35356067; PMCID: PMC8942165. https://pubmed.ncbi.nlm.nih.gov/35356067/

Yau K, Chan CT, Abe KT, Jiang Y, Atiquzzaman M, Mullin SI, Shadowitz E, Liu L, Kostadinovic E, Sukovic T, Gonzalez A, McGrath-Chong ME, Oliver MJ, Perl J, Leis JA, Bolotin S, Tran V, Levin A, Blake PG, Colwill K, Gingras AC, Hladunewich MA. Differences in mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine immunogenicity among patients undergoing dialysis. CMAJ. 2022 Feb 28;194(8):E297-E305. doi: 10.1503/cmaj.211881. Epub 2022 Feb 3. PMID: 35115375; PMCID: PMC9053976. https://pubmed.ncbi.nlm.nih.gov/35115375/

Atiquzzaman M, Zheng Y, Er L, Djurdjev O, Singer J, Krajden M, Balamchi S, Thomas D, Oliver MJ, Levin A. COVID-19 vaccine effectiveness in patients with non-dialysis-dependent chronic kidney diseases: findings from a population-based observational study from British Columbia, Canada. Kidney Int. 2022 Dec;102(6):1420-1423. doi: 10.1016/j.kint.2022.08.027. Epub 2022 Sep 11. PMID: 36103954; PMCID: PMC9464316. https://pubmed.ncbi.nlm.nih.gov/36103954/

McEvoy CM, Hu Q, Abe KT, Yau K, Oliver MJ, Levin A, Gingras AC, Hladunewich MA, Yuen DA. Humoral Responses in the Omicron Era Following 3-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients. Transplant Direct. 2022 Dec 7;9(1):e1401. doi: 10.1097/TXD.0000000000001401. PMID: 36518793; PMCID: PMC9742098. https://pubmed.ncbi.nlm.nih.gov/36518793/

Yau K, Enilama O, Levin A, Romney MG, Singer J, Blake P, Perl J, Leis JA, Kozak R, Tsui H, Bolotin S, Tran V, Chan CT, Tam P, Dhruve M, Kandel C, Estrada-Codecido J, Brown T, Siwakoti A, Abe KT, Hu Q, Colwill K, Gingras AC, Oliver MJ, Hladunewich MA. Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol. Can J Kidney Health Dis. 2023 Mar 20;10:20543581231160511. doi: 10.1177/20543581231160511. PMID: 36950028; PMCID: PMC10028441. https://pubmed.ncbi.nlm.nih.gov/36950028/

Wing S, Thomas D, Balamchi S, Ip J, Naylor K, Dixon SN, McArthur E, Kwong JC, Perl J, Atiquzzaman M, Yeung A, Yau K, Hladunewich MA, Leis JA, Levin A, Blake PG, Oliver MJ. Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period. Clin J Am Soc Nephrol. 2023 Apr 1;18(4):491-498. doi: 10.2215/CJN.0000000000000108. Epub 2023 Mar 2. PMID: 36723290. https://pubmed.ncbi.nlm.nih.gov/36723290/

Roushani J, Thomas D, Oliver MJ, Ip J, Yeung A, Tang Y, Brimble KS, Levin A, Hladunewich MA, Cooper R, Blake PG. Clinical Outcomes and Vaccine Effectiveness for SARS-CoV-2 Infection in People Attending Advanced CKD Clinics: A Retrospective Provincial Cohort Study. Clin J Am Soc Nephrol. 2023 Apr 1;18(4):465-474. doi: 10.2215/CJN.0000000000000087. Epub 2023 Feb 16. PMID: 36795940. https://pubmed.ncbi.nlm.nih.gov/36795940/

PITSTOP RCT - Paramedic Initiated Treatment of Sepsis Targeting Out-of-Hospital Patients Randomized Controlled Trial

Principal investigator
Dr. Damon Scales, Sunnybrook Health Sciences Centre

Recruitment Status
Recruiting

Summary
The PITSTOP RCT is a pragmatic 2x2 factorial randomized controlled trial that will test whether prompt recognition of sepsis by paramedics in the field followed by (1) early intramuscular antibiotics versus placebo and/or (2) early liberal intravenous fluids versus usual fluid management leads to more lives saved.

The study involves the administration of Ceftriaxone by intramuscular injection or placebo comprised of 0.9% NaCl (sodium chloride). Ceftriaxone is approved by Health Canada and all study procedures follow the recommendations of the approved product monograph. The study also involves the administration of 2 litres of intravenous 0.9% NaCl (sodium chloride) regardless of blood pressure, compared to usual IV fluid administration according to the standard Medical Directive.

The trial intervention will be delivered by paramedics working in participating Emergency Medical Services: currently Peel and Halton in Ontario, with plans to add additional services across Canada. The primary outcome for the trial is hospital survival. The anticipated sample size is 2040 patients recruited over a 4 to 5 year period.

ClinicalTrials.gov (NCT#)
NCT03068741

Trial email
pitstop@sunnybrook.ca

Trial Locations (city, province, country)
Halton, Peel and Toronto Paramedic Services

Social media links
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TESTING-ON - Therapeutic Evaluation of STeroids in IgA Nephropathy Global – Post-Trial ObservatioNal

Principal investigator
Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre

Recruitment Status
Recruiting

Summary
TESTING-ON is the follow up of the TESTING study where participants were given a 6–9-month course of oral methylprednisolone (a steroid). The purpose of this study is to evaluate the long-term effects and safety of oral methylprednisolone given with routine treatment, at preventing kidney failure in patients who have IgA nephropathy and are at high risk of progression to end stage kidney disease (ESKD)

The trial Primary Objective is to determine if adding methylprednisolone to optimal background care reduces the risk of kidney failure, defined as a composite of end-stage kidney disease (ESKD), a 40% reduction in eGFR or death due to kidney disease, in patients with progressive IgA nephropathy

Approximately 366 people are estimated to participate.

ClinicalTrials.gov (NCT#)
NCT05434325

Trial email
testingstudy@sunnybrook.ca

Trial Locations
Toronto, ON; London, ON; Montreal; QC; Vancouver, BC;

TESTING - Therapeutic Evaluation of STeroids in IgA Nephropathy Global low dose

Principal investigator
Dr. Michelle Hladunewich, Sunnybrook Health Sciences Centre

Summary
A multi-centre randomized double-blinded study to evaluate the long-term efficacy and safety of low dose oral methylprednisolone compared to matching placebo, on a background of routine RAS inhibitor therapy, in preventing kidney events in patients with IgA nephropathy and features suggesting a high risk of progression.

Primary outcomes were:

• Change in proteinuria from baseline at 6th and 12th months
• Mean change in eGFR at 6th and 12th months
• Progressive kidney failure, which is a composite of a 40 per cent decrease in eGFR, the development of end stage kidney disease (ESKD) defined as a need for maintenance dialysis or kidney transplantation, and death due to kidney disease
• Primary outcome specifically for the low-dose cohort

503 patients were enrolled in the study.

ClinicalTrials.gov (NCT#)
NCT01560052

Trial email
testingstudy@sunnybrook.ca

Trial Locations
67 sites (Canada – 8, Australia – 5, China – 41, India – 6, Malaysia – 6, Hong Kong – 1)

Publications

1. Lv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, Monaghan H, Zhao M, Barbour S, Reich H, Cattran D, Glassock R, Levin A, Wheeler D, Woodward M, Billot L, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Wang HY, Perkovic V; TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362. https://pubmed.ncbi.nlm.nih.gov/28763548/ 
2. Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527. https://pubmed.ncbi.nlm.nih.gov/26032537/

TILE - The TILE Pilot Study - Tinzaparin Lead‐In to Prevent the Post‐Thrombotic Syndrome Phase IV Study

Principal investigators
Dr Jean-Philippe Galanaud, Sunnybrook Health Sciences Centre

Recruitment Status
Terminated (Halted Prematurely)

Summary
The TILE study will be a multicenter, open‐label, assessor‐blinded RCT to assess whether a 3-week course of tinzaparin plus DOAC (Direct Oral Anticoagulants, rivaroxaban) is superior to DOAC alone to prevent post thrombotic syndrome after a first acute common femoral or iliac DVT. The TILE pilot study is a multicenter, open‐label, assessor‐blinded pilot RCT that will assess whether performing such a study is feasible and to determine the sample size of the definitive study. 60 participants will be enrolled in this trial.

ClinicalTrials.gov (NCT#)
 NCT04794569

Trial email
tile@sunnybrook.ca

Trial Locations
Hamilton, Toronto & Ottawa, Ontario; Montreal, Quebec