Evaluating PROCRIT In Intensive Care Unit Patients
Results from an investigational study researching the use of PROCRIT (Epoetin alfa) in medical, surgical and trauma patients admitted to an intensive care unit (ICU). The study was sponsored by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
The primary objective of the study was to determine whether administration of PROCRIT would decrease the number of critically ill patients who received a red blood cell (RBC) transfusion after admission to the ICU. There was no significant difference in the percentage of patients who received a RBC transfusion between the PROCRIT and placebo groups. However, the hemoglobin increase was greater in the PROCRIT group. Despite the lack of transfusion reduction, the study showed that treatment with PROCRIT significantly reduced mortality, particularly in trauma patients admitted to the ICU.
"The improvement in mortality findings are encouraging and this is a potentially important finding in this clinical setting," said Howard Corwin, M.D., Dartmouth-Hitchcock Medical Center, Hanover, NH.
This study was a prospective, randomized, double-blind, placebo-controlled, multi-center trial of patients aged 18 years or older who were admitted to an ICU for two days or more with a hemoglobin (Hb) less than 12 grams per deciliter of blood (g/dL). A total of 1,460 patients received either PROCRIT (n=733) or placebo (n=727) via subcutaneous injection on the first day of the study. For patients who remained in the hospital, treatment was specified for a total of three weekly doses (days 1, 8 and 15).
The primary endpoint was the percent of patients receiving any RBC transfusion through day 29. Secondary endpoints were RBC units transfused through day 42, change in Hb from baseline to day 29 and mortality at days 29 and 140. Analyses by the prospectively identified admission groups (trauma, surgery non-trauma and medical non-trauma) were performed similarly to the overall population.
There was no significant difference in the percentage of patients who received a RBC transfusion at day 29 between the PROCRIT and placebo groups (46% vs. 48.3%, p=0.34; relative risk 0.95, 95% confidence interval (CI), 0.85, 1.06). In addition, there was no difference between treatment groups in the total number of RBC units transfused through study day 42.
As noted by the authors, the most likely explanation for the lack of transfusion reduction was a change in transfusion practice. In two prior trials in critically ill patients, the PROCRIT group did achieve a reduction in RBC transfusions. In these studies, the mean pre-transfusion Hb concentration was 8.5 g/dL. In contrast in this trial, the mean pre- transfusion Hb concentration observed was 8.0 g/dL and the percentage of patients transfused was lower.
Mortality at study day 29 was significantly lower in the PROCRIT group (Kaplan-Meier (K-M) estimates: 8.5% vs. 11.4%, p=0.02). The mortality benefit with PROCRIT was most apparent in the trauma subgroup (K-M estimates: 3.5% vs. 6.6%, p=0.04). The mortality pattern at day 140 was similar for the overall group (K-M estimates: 14.2% vs. 16.8%, p=0.08) and the trauma subgroup (K-M estimates: 6.0% vs. 9.2%, p=0.08). The adjusted hazard ratios confirmed the mortality findings for trauma patients at days 29 (0.37, 95% CI, 0.19, 0.72) and 140 (0.40, 95% CI, 0.23, 0.69). The increase in Hb at day 29 was greater for patients who received PROCRIT (1.6 plus or minus 2.0 g/dL for patients receiving PROCRIT vs. 1.2 plus or minus 1.8 g/dL for patients receiving placebo, p<0.001).
As expected in a population of critically ill patients, adverse events and serious adverse events were frequent. A total of 690 (94.8%) PROCRIT patients and 680 (94.4%) placebo patients experienced at least one adverse event. Similarly, 44% of PROCRIT patients and 43.5% of placebo patients experienced a serious adverse event (SAE). However, there was no significant difference between the PROCRIT and placebo groups in the overall incidence of adverse and serious adverse events. There was a significant increase in thrombotic vascular adverse events associated with PROCRIT therapy (16.5% vs. 11.5%, p=0.008; hazard ratio 1.41, 95% CI, 1.06, 1.86). Post-hoc analyses demonstrated that thrombotic vascular events were higher as compared to placebo in the PROCRIT patients who did not receive heparin at baseline (20.3% for PROCRIT vs. 12.8% for placebo, p=0.008; hazard ratio 1.58, 95% CI, 1.09, 2.28), but were not higher in patients who received heparin (12.3% for PROCRIT vs. 10.2% for placebo, p=0.41; hazard ratio 1.16, 95% CI, .075, 1.80).
About PROCRIT (Epoetin alfa)
PROCRIT can be used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.