William E Mitch

Publications (2)8.62 Total impact

• Article: OPPORTUNITY™: a large-scale randomized clinical trial of growth hormone in hemodialysis patients.

  Joel D Kopple, Alfred K Cheung, Jens Sandahl Christiansen, Christian Born Djurhuus, Meguid El Nahas, Bo Feldt-Rasmussen, William E Mitch, Christoph Wanner, Marie Göthberg, Talat Alp Ikizler
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  ABSTRACT: Adult maintenance hemodialysis (MHD) patients experience high mortality and morbidity and poor quality of life (QoL). Markers of protein-energy wasting are associated with these poor outcomes. The OPPORTUNITY™ Trial examined whether recombinant human growth hormone (hGH) reduces mortality in hypoalbuminemic MHD patients. Secondary end points were effects on number of hospitalizations, cardiovascular events, lean body mass (LBM), serum proteins, exercise capacity, QoL and adverse events. We performed a randomized, double-blind, placebo-controlled, multicenter multinational trial stratified for diabetic status. Clinically, stable adult MHD patients with serum albumin <4.0 g/dL were randomized to subcutaneous injections of hGH, 20 μg/kg/day, or placebo. Planned treatment duration was 24 months for 2500 patients. The trial was terminated early due to slow recruitment. Seven hundred and twelve patients were randomized until trial termination; 695 patients received at least one dose of trial medication. Mean treatment duration was 20 weeks (no completers). There were no differences between groups in all-cause mortality, cardiovascular morbidity or mortality, serum albumin, LBM, physical exercise capacity or QoL. The hGH group, compared to placebo, displayed a reduction in body weight, total body fat, serum high-sensitivity C-reactive protein and possibly homocysteine and an increase in serum high-density lipoprotein-cholesterol and transferrin levels. Although the OPPORTUNITY™ Trial was terminated early, treatment with hGH, compared to placebo, improved certain cardiovascular risk factors but did not reduce mortality, cardiovascular events or improve nutritional factors or QoL. The power for showing differences was substantially reduced due to the marked decrease in treatment duration and sample size.
  Nephrology Dialysis Transplantation 07/2011; 26(12):4095-103. · 3.40 Impact Factor
• Article: OPPORTUNITY: a randomized clinical trial of growth hormone on outcome in hemodialysis patients.

  Joel D Kopple, Alfred K Cheung, Jens Sandahl Christiansen, Christian Born Djurhuus, Meguid El Nahas, Bo Feldt-Rasmussen, Martin Lange, William E Mitch, Christoph Wanner, Jonas Wiedemann, T Alp Ikizler
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  ABSTRACT: 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 Trial will examine whether GH reduces mortality and morbidity and improves overall health in hypoalbuminemic MHD patients. 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. 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 microg/kg per day) or placebo for 104 weeks. Key inclusion criteria include clinically stable and well-dialyzed (Kt/V > or =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. The OPPORTUNITY 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.
  Clinical Journal of the American Society of Nephrology 10/2008; 3(6):1741-51. · 5.23 Impact Factor