A randomised, double-blind, sham-controlled study of granulocyte/monocyte apheresis for moderate to severe Crohn's disease
OBJECTIVES Activated granulocytes and monocytes may contribute to the pathogenesis of Crohn's disease (CD). In small, uncontrolled studies, granulocyte/monocyte apheresis (GMA) has shown promise in treating CD. We conducted a randomised, double-blind study to compare GMA with a sham procedure in patients with moderate to severe CD. DESIGN Patients with active CD as defined by a Crohn's Disease Activity Index (CDAI) of 220-450 were randomly allocated in a 2:1 ratio to treatment with GMA using the Adacolumn Apheresis System (JIMRO, Takasaki, Japan) or sham apheresis. Ten apheresis sessions were scheduled over a 9-week period, and efficacy was evaluated at week 12. The primary end point was the proportion of patients achieving clinical remission (CDAI score =150 without use of prohibited drugs). RESULTS Clinical remission was achieved by 17.8% of patients in the GMA group (n=157) compared with 19.2% of those in the sham control group (n=78) (absolute difference -1.4% (95% CI-12.8% to 8.5%), p=0.858). Clinical response (defined as a =100-point decrease in CDAI) was achieved by 28.0% and 26.9% of patients in the GMA and sham groups, respectively (p=1.000). The two treatments produced similar changes from baseline in CDAI and quality of life, as well as in disease severity assessed endoscopically. The incidence and types of adverse events did not differ between groups. CONCLUSIONS GMA was well tolerated, but this study did not demonstrate its effectiveness over a sham procedure in inducing clinical remission or response in patients with moderate to severe CD. CLINICAL TRIAL REGISTRATION NUMBER Clinical Trials.gov identifier NCT00162942.
A cluster-randomized controlled trial of a blood conservation algorithm in patients undergoing total hip joint arthroplasty
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.
Erythropoietin with iron supplementation to prevent allogeneic blood transfusion in total hip joint arthroplasty. A randomized, controlled trial
Annals of Internal Medicine. 2000;133((11):):845-54.
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.