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De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease
Warady BA, Barcia J, Benador N, Jankauskiene A, Olson K, Podracka L, Shavkin A, Srivaths P, Wong CJ, Petersen J
Pediatric Nephrology (Berlin, Germany). 2017;33((1):):125-137
Abstract
BACKGROUND Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naive patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. METHODS One-hundred sixteen pediatric ESA-naive subjects (aged 1-18 years) with CKD stages 3-5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL) in children ≥2 years. RESULTS In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0-12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL scores showed modest increases. CONCLUSIONS Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naive pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl.
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A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis
Sands BE, Sandborn WJ, Feagan B, Löfberg R, Hibi T, Wang T, Gustofson LM, Wong CJ, Vandervoort MK, Hanauer S, et al
Gastroenterology. 2008;135((2):):400-9.
Abstract
BACKGROUND & AIMS Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis. Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis. METHODS We evaluated the efficacy of granulocyte/monocyte apheresis in a randomized, double-blind, sham-controlled trial in patients with active moderate-to-severe ulcerative colitis (Mayo score 6-11) in community-based and tertiary care centers. As intervention, we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System (JIMRO, Ltd, Takasaki, Japan) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study (N = 168) and in a smaller, companion study of identical design conducted in Europe and Japan (N = 47). RESULTS In the pivotal study, clinical remission rates (Mayo score 0-2, with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination) were 17% and 11% for the granulocyte/monocyte apheresis (n = 112)- and sham-treatment groups, respectively (n = 56; P = . 361). Clinical response (Mayo score reduction of ≥3 points from baseline) was observed in 44% and 39% of patients, respectively (P = . 620). Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response, and changes in Mayo and quality-of-life scores. The companion study and pooled data from both studies also yielded similar results. CONCLUSIONS In this study, granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis.
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A cluster-randomized controlled trial of a blood conservation algorithm in patients undergoing total hip joint arthroplasty
Wong CJ, Vandervoort MK, Vandervoort SL, Donner A, Zou G, MacDonald JK, Freedman J, Karkouti K, MacDonald SJ, Feagan BG
Transfusion. 2007;47((5):):832-41.
Abstract
BACKGROUND The optimum strategy for reducing allogeneic blood transfusion in patients undergoing total hip joint arthroplasty (THJA) is unknown. STUDY DESIGN AND METHODS The effectiveness of a comprehensive blood conservation algorithm (BCA) was evaluated by means of a cluster randomization trial. Thirty hospitals performing primary THJA were randomly assigned to implement the algorithm or to continue with usual care (UC). Subsequently, the institutional rate of allogeneic transfusion was determined for 60 consecutive patients who underwent surgery at each site. The BCA consisted of patient and provider education, hemoglobin-based recommendations for specific blood conservation strategies (recombinant human erythropoietin [rHuEPO] or autologous blood donation [ABD]) and transfusion guidelines. The main outcome measure was the institutional allogeneic transfusion rate. RESULTS One hospital withdrew consent after randomization, resulting in 14 hospitals assigned to BCA and 15 to UC. In the BCA arm, the institutional rates of rHuEPO use and ABD participation were 20. 1 and 27. 1 percent compared to 0. 6 and 25. 8 percent, respectively, in the UC arm. The allogeneic transfusion rate was substantially reduced in hospitals assigned to the BCA group (p = 0. 02; absolute risk reduction, 9. 6% [26. 1% UC vs. 16. 5% BCA]). Multivariate analysis of patient-level data showed that assignment to the UC arm was an independent risk factor for allogeneic transfusion (p = 0. 037; odds ratio, 1. 8; 95% confidence interval, 1. 0-3. 1) when adjusted for other prognostic factors. No differences were observed in the use of autologous blood. CONCLUSION A comprehensive approach to blood conservation was superior to UC for reducing allogeneic transfusion in patients undergoing THJA.
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Erythropoietin with iron supplementation to prevent allogeneic blood transfusion in total hip joint arthroplasty. A randomized, controlled trial
Feagan BG, Wong CJ, Kirkley A, Johnston DW, Smith FC, Whitsitt P, Wheeler SL, Lau CY
Annals of Internal Medicine. 2000;133((11):):845-54.
Abstract
BACKGROUND The optimum regimen of epoetin alfa for prevention of allogeneic blood transfusion is unknown. OBJECTIVE To determine whether a modified regimen of epoetin alfa reduces allogeneic blood transfusion in patients undergoing hip arthroplasty. DESIGN Randomized, double-blind, multicenter trial comparing two modified dose regimens of epoetin alfa with placebo. SETTING 13 teaching hospitals and 4 community hospitals in Canada. PATIENTS 201 patients undergoing primary hip arthroplasty who had a hemoglobin concentration of 98 to 137 g/L and did not predonate blood. INTERVENTION Patients were assigned in a 3:5:5 ratio to receive four weekly doses of epoetin alfa, 40 000 U (high-dose; n = 44) or 20 000 U (low-dose; n = 79), or placebo (n = 78), starting 4 weeks before surgery. All patients received oral iron supplementation, 450 mg/d, for 42 or more days before surgery. MEASUREMENTS The primary end point was allogeneic transfusion. Secondary end points were thromboembolic events and change in reticulocyte count and hemoglobin concentration. RESULTS Both modified epoetin alfa regimens significantly reduced the need for allogeneic transfusion: Five (11.4%) patients in the high-dose group (P = 0.001) and 18 (22. 8%) patients in the low-dose group (P = 0.003) had transfusion, compared with 35 (44.9%) patients in the placebo group. The hematologic response was substantial in patients who received epoetin alfa. In the high-dose group, low-dose group, and placebo group, the preoperative increase in reticulocyte count was 58.8, 37. 0 and 1.8 x 10(9) cells/L (P < 0.001), respectively, and the increase in hemoglobin concentration was 19.5, 17.2, and 1.2 g/L (P < 0.001). The incidence of thromboembolic events did not differ among groups. CONCLUSIONS Both modified epoetin alfa regimens were effective compared with placebo in reducing allogeneic transfusion in patients undergoing hip arthroplasty. Patients who received high-dose epoetin alfa had the lowest transfusion rate.