Opportunity™

Abstract

Background: The mortality rate of maintenance hemodialysis (MHD) patients remains high. Measures of protein-energy wasting, including hypoalbuminemia, are strongly associated with their high mortality. Growth hormone (GH) may improve lean body mass (LBM) and serum albumin levels, and health-related quality of life (HRQoL), which are significantly and positively associated with survival in MHD patients. The OPPORTUNITY TM Trial will examine whether GH reduces mortality and morbidity and improves overall health in hypoalbuminemic MHD patients.Hypothesis: The primary hypothesis is that daily recombinant human GH injections, compared with placebo, improve survival in hypoalbuminemic MHD patients. Secondary hypotheses are that GH improves morbidity and health, including number of hospitalized days, time to cardiovascular events, LBM, serum protein and inflammatory marker levels, exercise capacity, and HRQoL, and has a favorable safety profile.Design/Measurements: This is a prospective, double-blind, multicenter, randomized clinical trial involving 2500 MHD patients, up to 50% with diabetes mellitus, from 22 countries. Patients are randomized in a 1:1 ratio to receive daily injections of GH (20 g/kg per day) or placebo for 104 weeks. Key inclusion criteria include clinically stable and well-dialyzed (Kt/V >1.2) adult MHD patients with serum albumin <4.0 g/dl. Exclusion criteria include active malignancy, active proliferative or severe nonproliferative diabetic retinopathy, uncontrolled hypertension, chronic use of high-dose glucocorticoids, or immunosuppressive agents and pregnancy.Conclusions: The OPPORTUNITY TM Trial is the first large-scale randomized clinical trial in adult MHD patients evaluating the response to GH of such clinical endpoints as mortality, morbidity, markers of body protein mass, inflammation, exercise capacity, and HRQoL.

Impact of Fatigue on Outcomes in the Hemodialysis (HEMO) Study

“…These findings are consistent with reports demonstrating that dialysis patients with laboratory evidence of malnutrition and/or inflammation have low levels of physical activity, higher fatigue and mortality [1,2,8,26]. Perhaps improving nutrition or increasing albumin levels by pharmacological interventions [27] in these patients will improve not only quantity but also quality of life by reducing fatigue.…”

Factors related to fatigue in Chinese patients with end-stage renal disease receiving maintenance hemodialysis: a multi-center cross-sectional study

“…The sleep disorder cause to fatigue has been hypothesized through two mechanisms: excessive daytime sleepiness and increased level of certain inflammatory cytokines. 35 Our finding suggests that fatigue significantly related to the self-reported sleep quality. Measures to relieve sleep disorder may decrease fatigue and perhaps improve these people's quality of life, functional health status, and outcome.…”

Effect of high-protein meals during hemodialysis combined with lanthanum carbonate in hypoalbuminemic dialysis patients: findings from the FrEDI randomized controlled trial

“…Prior studies have shown that serum albumin levels <4.0 g/dL are predictive of higher death risk in hemodialysis patients, and that even mild increases in serum albumin of !0.2 g/dL over time are associated with improved survival, lower hospitalization risk, and reduced treatment costs [19][20][21]24]. While the degree to which a decline in serum albumin reflects protein-energy wasting, increased protein catabolism, dialytic protein and amino acid losses and inflammation in these studies remains unclear, large observational studies show that moderate increases in protein intake are also associated with greater survival compared to reductions in protein intake in this population.…”

“…This serum albumin threshold was selected according to prior data demonstrating associations with lower mortality, hospitalization risk and treatment costs in hemodialysis patients [19][20][21]. Secondary outcomes included (i) achievement of the individual endpoints of the primary composite outcome, (ii) change in chronic kidney disease-mineral and bone disease biochemical parameters [serum calcium, parathyroid hormone (PTH), alkaline phosphatase], (iii) change in nPCR, (iv) change in serum electrolytes that correlate with protein intake (serum bicarbonate, potassium), (v) change in …”