November 21, 2010

ASN 2010 Late Breaking Clinical Trial Results | SHARP, Preclot, more

The late breaking clinical trials session from the 2010 American Society of Nephrology meeting was held on November 20, 2010.  The following are summaries of the clinical trial results.  Where available, links to additional online resources are included.  Access to the full details of these studies awaits publication in peer reviewed journals.

The Sharp Collaborative Group.  Should We Reduce LDL Cholesterol in Patients with Chronic Kidney Disease? The Results of the Study of Heart and Renal Protection (SHARP)

In this eagerly awaiting trial, patients with CKD (men with Cr ≥1.7 mg/dL (150 µmol/L)  or women with Cr ≥1.5 mg/dL (130 µmol/L), no history of myocardial infarction or coronary revascularization and clinical uncertainty if lipid lowering therapy was warranted, patients were randomized to lipid lowering therapy (simvastatin or simvastatin/ezetimibe) vs placebo (see slide 4 of the powerpoint presentation to view the complex details of randomization).

The primary outcome (major atherosclerotic events defined as a composite of coronary death, MI, non-haemorrhagic stroke, or any revascularization) was reduced by 17%.  See the slide below.  Similar reductions were noted in both patients on dialysis and those with CKD but not yet on dialysis.  No difference was seen in side effects including those related to muscle/liver toxicity and malignancy.

View the online resource web site

View the slides presented at the 2010 ASN Meeting

Brenda Hemmelgarn et al.  Prevention of Dialysis Catheter Lumen Occlusion with RT-PA versus Heparin (Preclot): A Randomized Trial

In this randomized controlled trial (see published trial design) looking at central venous catheters (CVC) in hemodialysis patients, patients were randomized to receive rt-PA 1 mg per lumen once per week to lock their CVC post dialysis or  heparin 5,000 units per ml after each dialysis session.  The rt-PA arm resulted in a significant reduction in catheter malfunction (primary outcome) and bacteremia (secondary outcome).  No signficant difference in bleeding events were noted between arms.

Prospective Randomized Trials of More Frequent Hemodialysis: The Frequent Hemodialysis Network (FHN)

Trials of Daily In-Center and Nocturnal Home Hemodialysis

Nathan W. Levin et al  for the ‘Daily’ Study

As reported in the New England Journal of Medicine paper released to coincide with the oral presentation,  this randomized controlled trial comparing conventional thrice weekly dialysis to frequent “daily” dialysis revealed that  more frequent dialysis resulted in improvement in the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access.

Michael Rocco et al for the Nocturnal’ Study.

This randomized controlled trial comparing conventional thrice weekly dialysis to nocturnal dialysis failed to show that  frequent, nocturnal dialysis resulted in improvements in the composite outcomes of death or change in left ventricular mass, or death or change in a physical-health composite score.

Pablo E. Pergola et al.  Effect of Bardoxolone Methyl on Renal Function in Patients with Chronic Kidney Disease (CKD) and Type 2 Diabetes Mellitus

This report documented clinical outcomes at 24 weeks from a 52 week trial comparing bardoxolone methyl vs placebo in patients with diabetes and chronic kidney disease.  227 patients with eGFR ranging from 20-45 ml/min were randomized.  At 24 weeks, those in the treatment arm experienced an increase in eGFR of 10.1% (p < 0.0001) compared to placebo.    Side effects such as muscle spasms, nausea, anorexia and hypomagnesemia were significantly more common in the active treatment arm.  Formal measurement of GFR, hard clinical endpoints and eGFR response to drug withdrawal were not reported.

Howard Trachtman et al. Results of the Multicenter FSGS Clinical Trial in Children and Young Adults

In this randomized controlled trial of cyclosporine vs mycophenolate mofetil + dexamethasone in children and young adults with steroid resistant focal segmental glomerulosclerosis, no difference was found in the primary outcome of partial or complete remission of proteinuria.  Of note, the rate of complete remission was low in both arms and disease relapse was frequent after drug withdrawal.

Steven Fishbane et al.  Primary Safety and Efficacy Results from Four Phase 3 Randomized, Active-controlled, Open-label Studies of Hematide/Peginesatide among CKD Dialysis and Nondialysis Patients

This presentation included pooled analysis of 4 distinct studies, 2 completed in patients on dialysis (EMERALD 1 and 2) and 2 completed in CKD patients not yet on dialysis (PEARL 1 and 2).  In the pooled analysis of these 4 trials designed to test for non-inferiority in correcting or maintaining haemoglobin in the target range, the primary efficacy endpoint met the statistical criteria for non-inferiority. While the safety endpoint met the criteria for non-inferiority in the pooled analysis, subgroup analysis of non-dialysis patients (PEARL trials) revealed the frequency of events was higher in the peginesatide group than the comparator group.  Such a difference was not seen in the subgroup on dialysis.

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Clinical Trial Results, Experimental Nephrology