The Concord Nephrology Clinical Trials Unit has an active program of clinical research. A major theme of the program is involvement in studies designed to improve outcomes for people with kidney disease. Our program includes studies initiated both by the Concord Unit and by collaborators from other Australian and international units. The unit has strong links with the leading edge of research in kidney disease. Two of our staff, A/Prof Martin Gallagher and A/Prof Meg Jardine have appointments at a leading, international research organisation, The George Institute for Global Health, and are both leading international research collaborations. Dr Shaundeep Sen brings expertise in vascular function and uraemic toxin research. Dr Celine Foote is leading studies on the impact of managing advanced kidney disease in elderly people. Members of the team are on the steering committees of several AKTN projects (A/Prof Jardine and Dr Ritchie) and the AKTN Haemodialysis Working Group (A/Prof Jardine). The unit is also the lead site for the SONAR and TESTING studies.
C/- Department of Renal Medicine, 4W
T: 9767 6576
F: 9767 6254
The 'FINESSE' trial:
Filtration In the Neuropathy of End Stage kidney disease Symptom Evolution Clinicaltrials.gov registration number: ACTRN 12609000615280.
This trial was initiated by staff of the Renal Units of Concord and Royal Prince Alfred Hospitals. It is being run by a collaboration of dialysis, neuropathy and trial experts in a number of Australian Renal units. The study will address the pressing need for novel strategies to impact on the pain and disability burden of the neuropathy associated with chronic kidney disease (uraemic neuropathy). With no recognized disease course-altering treatment other than transplantation, there is a pressing need for novel strategies to mitigate this disease burden. FINESSE randomised 124 people undergoing maintenance dialysis to HDF or standard dialysis for up to 9 years to determine whether HDF reduces the occurrence and slows the progression of uraemic neuropathy in patients requiring regular maintenance haemodialysis. Recruitment closed in March 2013 and the trial is due to finish in March 2018.
The IMPROVE-CKD trial:
A randomised, double-blind, placebo-controlled trial to assess the effect of phosphate reduction with lanthanum carbonate on arterial compliance and vascular calcification in patients with chronic kidney disease stages 3b-4 Clinicaltrials.gov registration number: ACTRN12610000650099
Chronic kidney disease (CKD) is a significant health problem and is associated with an increased risk of cardiovascular (CV) disease. Vascular calcification and arterial stiffness (stiffening of the blood vessels and arteries) are very common in people with CKD, and are linked to increased death from CV events. This study aims to examine the ways in which treatment with a phosphate binder, Lanthanum Carbonate, may reduce vascular calcification and arterial stiffness to decrease CV events. Recruitment closed in January 2017 and the trial will finish in December 2018.
The 'PEXIVAS' trial:
Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis: an international randomized controlled trial. Clinicaltrials.gov registration number: NCT00987389.
This trial aims to study the combination of Plasma Exchange and either standard-dose or reduced-dose glucocorticoids in the treatment of ANCA-associated vasculitis. Eligible patients with ANCA-associated vasculitis were randomised 1:1 to receive Plasma Exchange/No Plasma Exchange, then within each PLEX group, randomised 1:1 to receive standard dose / reduced dose glucocorticoids. Participants also received standard immunosuppressive therapy. The follow-up period for all patients will be between 5 and 7 years duration. The primary outcome measure was time to the composite endpoint of all-cause mortality or end-stage renal disease. This trial is a large, multi-centre, international randomised controlled trial coordinated centrally out of the Birmingham Clinical Trials Unit, on behalf of the European Vasculitis Study Group (UK) and the Vasculitis Clinical Research Consortium (USA). The AKTN is facilitating the Australian and New Zealand arm of the trial. Recruitment closed in November 2016 and the trial will finish later this year.
The REMOVAL-HD trial:
A single arm, non-randomised device trial to assess the effect of the Theranova Dialyser on albumin and uraemic solutes in patients with Stage V chronic kidney disease requiring haemodialysis Clinicaltrials.gov registration number: ACTRN12616000804482
The REMOVAL-HD Study includes haemodialysis patients with AV fistula or graft and aims to use the Theranova dialyser to increase the removal of the larger middle-molecules without a decrease in serum albumin. The study is a single armed, open label, pivotal device trial and the primary outcome is change in pre-dialysis concentration of serum albumin between baseline and six months. Recruitment has just begun.
The REPRISE trial:
A Phase 3b, Multi-center, Randomized-withdrawal, Placebo-controlled, Double-blind, Parallel-group Trial to Compare the Efficacy and Safety of Tolvaptan (45 to 120 mg/day, Split-dose) in Subjects with Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease Clinicaltrials.gov registration number: NCT02160145 This multi-centre, randomized-withdrawal, placebo-controlled, double-blind, parallel-group trial aims to compare the efficacy and safety of tolvaptan in subjects with ADPKD. CRGH completed study participation in 2016.
The ROCKIES trial:
A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of the Safety and Efficacy of Roxadustat in the Treatment of Anemia in Dialysis Patients Clinicaltrials.gov registration number: NCT02273726 This is a Phase 3, multicenter, randomized, open-label, active-controlled study to evaluate the safety and efficacy of roxadustat compared to epoetin alfa for the treatment of anemia in dialysis patients. Patients on hemodialysis (HD) or peritoneal dialysis (PD) who have been treated with an erythropoietin analogue or have an indication for treatment with an erythropoietin analogue will be evaluated for eligibility and randomized at a 1:1 ratio to treatment with roxadustat (with discontinuation of prior erythropoietin analogue therapy) or to an active-control group treated with epoetin alfa. Recruitment closed in 2015 and the study is expected to finish early 2018.
The SHARP-ER trial:
The Study of Heart And Renal Protection - Extended Review Clinicaltrials.gov registration number: NCT00125593.
Patients with CKD have significant increases in cardiovascular morbidity and mortality, hospitalisation rates and reduced quality of life, with few treatments proven to reduce this increasing burden of disease. The Study of Heart and Renal Protection (SHARP) reported a 17% reduction in its primary outcome of major atherosclerotic events, with 2028 participants recruited in Australia, New Zealand and Malaysia. Extending the follow up of these participants for a further 5 years will provide unique data to explore the long term effects of cholesterol lowering treatment upon major atherosclerotic events, cancer and non-vascular mortality; to better understand factors that influence the long term progression of CKD; and to explore the economic impact of CKD on patients and their families. This study closed in 2016.
The SONAR Study:
A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects with Type 2 Diabetes and Nephropathy SONAR: Study of Diabetic Nephropathy with Atrasentan Clinicaltrials.gov registration number: NCT01858532.
The SONAR study is examining the effect of atrasentan (compared to placebo) upon the progression of kidney disease in patients with diabetic nephropathy. This is an international multi-centre study. The study recruited patients with diabetes and impaired kidney function who had significant amounts of protein in their urine. The study is aiming to address one of the major gaps in our treatments to prevent the progression of diabetic kidney disease, that of treatments that reduce urine protein loss but also do not reduce blood pressure too much. It will also provide important additional insights into whether such urine protein reduction slows the progression of such kidney disease. The Concord Nephrology Clinical Trials Unit is the lead site for this study in NSW, QLD and VIC. Recruitment closed in February 2017 and the study is expected to end in November 2018.
The TESTING Study:
Therapeutic Evaluation of Steroids in IgA Nephropathy Global low dose study Clinicaltrials.gov registration number: NCT01560052 IgA nephropathy is a condition that occurs around the world and can lead to progressive loss of kidney function. There is conflicting evidence on whether treatment with corticosteroids will improve outcomes and slow the loss of kidney function. The TESTING study will randomise people with biopsy-proven IgA nephropathy and proteinuria to a 6 month course of corticosteroids or placebo.
The TIMELY Study:
Treatment modalities for the Infirm Elderly with end stage kidney disease: the TIMELY study An increasing number of elderly patients are reaching end-stage kidney disease (ESKD). Little is known about the outcomes of elderly patients whether they choose to be managed supportively or by dialysis. TIMELY will identify elderly patients with ESKD and follow them for a median of 2 years. It is a pilot study for the larger TIMELY study, which is currently before funding bodies with a view to national study of elderly ESKD patients, and is designed to demonstrate feasibility. These studies will define the use of both dialysis and supportive care locally and nationally, as well as provide robust and comparable estimates of mortality and other patient-centred outcomes with the two treatment modalities.
RESOLVE study: (SLHD staff includes M Jardine, M Gallagher, P Snelling – Regional Steering Committee Members; Monique Thompson, In Cho - RESOLVE Nurses Committee, Shaundeep Sen – Principle Investigator).
People with dialysis are at high risk of death, and the best way to provide many aspects of treatment has not been properly assessed. In particular, the optimal concentration of sodium in the dialysis fluid is unknown. As a result, a wide variety of different dialysate sodium concentrations are selected arbitrarily in different dialysis units. Dialysis patients continue to be exposed to these different concentrations without any mechanism for determining if the concentration selected affects patient outcomes. RESOLVE is a large quality improvement study involving more than 400 dialysis centres around the world. It will allocate 2 of the currently used default dialysis sodium concentrations at random rather than arbitrarily, and thus will be able to determine which dialysate sodium concentration is optimal so that all sites can receive the optimal concentration once it is established. Clinicaltrials.gov registration number NCT02823821.
Higher Degree Students:
- Dr Celine Foote
Principal Investigator (TIMELY)
Associate Investigator (REMOVAL, REPRISE, RESOLVE, ROCKIES, SONAR)
- A/Prof Martin Gallagher
Coordinating Principal Investigator (SONAR)(lead site)
Associate Investigator (IMPROVE, PEXIVAS, TESTING, REPRISE, ROCKIES, REMOVAL)
- A/Prof Charles George
Associate Investigator (TESTING)
- A/Prof Meg Jardine
Director of Research
Coordinating Principal Investigator (FINESSE)
Principal Investigator (REPRISE)
Associate Investigator (IMPROVE, PEXIVAS, ROCKIES, REMOVAL, SONAR, TESTING)
- Dr Mona Razavian
Coordinating Principal Investigator (TESTING) (lead site)
Associate Investigator (FINESSE, IMPROVE, PEXIVAS, REMOVAL, REPRISE, SONAR)
- Dr Angus Ritchie
Associate Investigator (PEXIVAS, REMOVAL, REPRISE, ROCKIES, SONAR)
- Dr Shaundeep Sen,
Head of Department Principal Investigator (REMOVAL, RESOLVE)
Associate Investigator (IMPROVE, REPRISE, ROCKIES, SONAR)
- Dr Roger Wyndham
Principal Investigator (IMPROVE, ROCKIES)
Associate Investigator (REMOVAL, SONAR, TESTING)
- Ms Frances Daley
Clinical Trial Coordinator
- Dr Brendan Smyth, PhD. Concord RESOLVE Fellow
- Dr Louisa Sukkar, PhD.
Publications and Presentations
- Louisa Sukkar, Daqing Hong, Muh Geot Wong, Sunil V. Badve, Kris Rogers, Vlado Perkovic, Michael Walsh, Xueqing Yu, Graham S. Hillis, Martin Gallagher, Meg Jardine. Effects of ischaemic conditioning on major clinical outcomes in people undergoing invasive procedures: A systematic review and meta-analysis. BMJ 2016 Nov 7;355:i5599. Doi: 10. 1136/bmj.i5599
- Hilary M Miller, Allison Tong, David J Tunnicliffe, Denise Campbell, Jule Pinter, Robert J Commons, Athan E, Craig JC, Gilroy N, Green J, Henderson B, Howell M, Stuart RL, van Eps C, Wong MG, de Zoysa J, Meg J Jardine. Identifying and integrating patient and caregiver perspectives for clinical practice guidelines on the screening and management of infectious microorganisms in hemodialysis units. Kidney International, 2016. Jul 8.
- AY Wang, C Sherrington, T Toyama, M Gallagher, A CASS, Y HIRAKAWA, Q Li, L Sukkar, P Snelling, M Jardine. Muscle strength, mobility, quality of life and falls in patients on maintenance haemodialysis: A prospective study. Nephrology 2016
- A Wang, J Ivany, V Perkovic, M Gallagher, M Woodward, M Jardine. Anticoagulants and antiplatelet agents for preventing central venous haemodialysis catheter malfunction in patients with end-stage kidney disease. Cochrane Database Syst Rev. 2016 Issue 3. Apr 4
- Nigwekar SU, Kang A, Zoungas S, Cass A, Gallagher MP, Kulshrestha S, Navaneethan SD, Perkovic V, Strippoli GFM, Jardine MJ. Interventions for lowering plasma homocysteine levels in dialysis patients. Cochrane Database Syst Rev. 2016 Issue 5. May 31
- Chan K, Giugliano R, Patel M, Abramson S, Jardine M, Zhao S, Perkovic V, Maddux F, Piccini J. Non-vitamin K anticoagulants in advanced chronic kidney disease and in patients on dialysis with atrial fibrillation. J Am Coll Cardiol. 2016 Jun 21;67(24):2888-99. doi: 10.1016/j.jacc.2016.02.08
- Woodward M, Hirakawa Y, Kengne A-P, Matthews DR, Zoungas S, Patel A, Poulter N, Grobbee R, Cooper M, Jardine M, Chalmers J. Prediction of ten-year vascuar risk amongst patients with diabetes: the AD-ON risk score. Diabetes, Obesity and Metabolism, 2016, 18(3) 289-94.
- Foote C, Kotwal S, Gallagher M, Cass A, Brown M, Jardine M. Survival Outcomes of Supportive Care versus Dialysis Therapies for Elderly Patients with End Stage Kidney Disease: a systematic review and meta-analysis. Nephrology 2016; 21 (3) 241-253
- Liyanage T, Ninomiya T, Wang A, Jun M, Neal B, Wong MG, Jardine M, Hillis G, Perkovic V. Effects of the Mediterranean diet on cardiovascular outcomes: A systematic review and meta-analysis. PLOS ONE. 2016 11(8)
- Canadian Society of Nephrology - Australian New Zealand Society of Nephrology Debate, November 2016, Chicago, USA
- Joint Asia-Pacific Congress of Nephrology and Australian and New Zealand Society of Nephrology Annual Scientific Meeting, Main Conference Invited Speaker, Session Co-chair, Education Update Invited Speaker, Satellite Meeting Invited Speaker, Perth, Australia, 2016
- Annual Conference of Chinese Association of Blood Purification Management Branch of Chinese Hospital Assocation. Plenary Speaker: 'Dialysate Sodium Concentration and Long Term Outcomes', 2016, Nanjing, China. KDIGO (international Kidney guidelines group) Diabetes Controversies Conference. Invited talks. Lifestyle & Dietary Interventions in DKD. 2016
||YEARS total $$
|NHMRC Project Grant (APP 1127085)
||Evaluation of the efficacy and safety of health service dialysate sodium practice on clinical outcomes.
||Rebecca L. Cooper Medical Research Foundation Grant
|| $ 25,000
Contact details for department
Head of Department: Dr Shaundeep Sen
Department/Unit: Renal Medicine
Telephone: (02) 9767 6576
Facsimile: (02) 9767 6254