Gardener’s Grove 2023 Proposed Trials
In no particular order, the proposed trials to be presented at Gardener’s Grove 2023 include:
Outcomes of a higher vs. lower hemodialysate bicarbonate concentration: A pragmatic cluster randomized trial
PIs: Amber Molnar and Samuel Silver
In Canada, healthcare providers generally use dialysate with a bicarbonate concentration from 32 mmol/L to 40 mmol/L. Observational studies suggest that a higher dialysate bicarbonate concentration may increase the risk of cardiovascular and infectious complications, but the optimal concentration for patient health is generally unknown.
To address this knowledge gap, Drs. Amber Molnar and Samuel Silver proposes conducting a pragmatic cluster randomized trial to compare the dialysate bicarbonate concentrations used in current practice to determine the optimal concentration for patient outcomes, focusing on a primary composite outcome of all-cause mortality and hospitalizations with secondary outcomes including cardiovascular death, hospitalizations and fractures.
Expanded vs. conventional hemodialysis: a large pragmatic cluster randomized trial
PI: Pavel Roshanov
In conventional hemodialysis, using high-flux hemodialysis filters removes small and smaller-sized molecule toxins, but does not effectively remove larger-sized middle molecules. These larger-sized middle molecules may contribute to fatigue, cardiovascular disease, increased infections, anemia, and other complications for patients who receive chronic maintenance hemodialysis.
A new class of filter – the medium cut-off (MCO) filter – is more permeable than conventional high-flux filters, which allows the passage of larger middle molecules, expanding the breadth of toxin removal. Small studies on the effect of MCO filter use show promising results in improving patient outcome, but were small, short and have risk of bias.
Dr. Pavel Roshanov proposed a pragmatic cluster randomized controlled trial testing the effects of MCO filters in hemodialysis to determine if its use on the primary outcome of hospitalizations and all-cause mortality, and secondary outcomes that include cardiovascular events, infection-related hospitalization, receipt of kidney transplantation, and healthcare-associated costs.
Impact of diuretic use on cardiovascular outcomes and mortality in patients on maintenance hemodialysis who have residual renal function
PI: Melissa Schorr
When patients start hemodialysis, they often maintain some urine output, which can be lost with time on dialysis. However, ongoing urine output is associated with improved cardiovascular outcomes and lower mortality, possibly due to improved control of extracellular fluid expansion, or fluid overload. A potential method that could control fluid overload is the use of diuretic medications to maintain urine output, but this has not been tested in a large scale randomized controlled trial.
To address this knowledge gap, Dr. Melissa Schorr proposed a large-scale randomized controlled trial testing different doses of diuretic medications to determine the optimal dose for persons on hemodialysis to control fluid overload and maintain a urine output of 200cc or more per day. The trial will focus on primary outcomes of reduced adverse cardiac events and all-cause mortality.
SOLUTETrial – Sodium fOr diaLysis oUTcome rEduction
PI: Conor Judge
Maintenance of blood pressure in persons on hemodialysis is vital, but can be very difficult. Sodium intake reduction is a cornerstone of blood pressure management in this population. A potential solution is the modification of sodium concentration in dialysate, and observational studies have shown a positive association between lower dialysate sodium concentration and lower blood pressure, lower interdialytic weight gain and lower anti-hypertensive medication use. One previous study showed no different in primary outcome of left ventricular mass index, despite differences in interdialytic weight gain.
RESOLVE, a separate pragmatic cluster randomized trial that will compare the effectiveness of two fixed dialysate sodium concentrations (137 mmol/L vs 140 mmol/L). Dr. Conor Judge proposed a cluster randomized controlled trial comparing zero sodium gradient (0 mmol/L) (which is dialysate sodium minus pre-dialysate plastma sodium results) with a fixed dialysate sodium of 138 mmol/L. This would essentially personalize the sodium concentration to the patient. The trial will evaluate the effectiveness on the primary outcome of cardiovascular events.
Finding the right blood pressure target for patients on dialysis: A cluster randomized trial
PI: Nav Tangri
What is known is that high blood pressure can lead to cardiovascular morbidity and mortality due to strokes, heart failure, left ventricular hypertrophy and arrhythmias, and lower blood pressure can lead to cramps, myocardial stunning and cerebrovascular ischemia. However, the optimal blood pressure targets for persons on dialysis is unknown.
To address this knowledge gap, Dr. Nav Tangri proposes a cluster randomize trial targeting a lower and higher predialysis systolic blood pressure target for persons on hemodialysis. The primary outcome would be major adverse cardiovascular events and secondary outcomes would include all hospitalizations and mortality, with possible substudies examining cramps, hypotensive episodes and cognitive function.
PREventing FracturEs in REnal Disease 2 – PREFERRED-2
PI: Kristin Clemens
Fragility Fractures of the spine, hips, wrists, shoulders, and pelvis are a leading cause of morbidity and can result in hospitalization, permanent disability, institutionalization, and death. Persons on hemodialysis have a risk of fracture that is more than five times higher than sex- and age-matched individuals with chronic kidney disease.
Denosumab is a medication approved in Canada that can be prescribed for persons on hemodialysis that may have a role in fracture risk reduction, though there have been few research studies on its efficacy and safety. Dr. Kristin Clemens proposed a large randomized pragmatic trial of denosumab in routine care hemodialysis centres to determine whether the care pathway with the medication vs. without effects the risk of fragility fracture.
We would like to thank all of the applicants who submitted proposals. The proposals that were submitted were all well written and discussed thoroughly by the Gardener’s Grove 2023 Proposal Review Committee.