Study Published in The Journal of the American Medical Association.
BRIDGEWATER, NJ — December 11, 2002 — Results of a new study published today in The Journal of the American Medical Association found that critically ill patients who received once weekly PROCRIT® (Epoetin alfa) were ten percent less likely to receive red blood cell transfusions (RBCs) than patients in the placebo group. In addition, there was a 19 percent reduction in the total units of RBCs transfused in the PROCRIT group versus the placebo group. The study was supported by Ortho Biotech Products, L.P., marketer of PROCRIT.
“While transfusion has been an integral part of clinical practice to treat anemia in critically ill patients, it also carries significant risks for some patients,” said co-principal investigator of the study, Howard L. Corwin, M.D., Dartmouth-Hitchcock Medical Center. “This study was designed to assess the efficacy of a weekly dosing schedule of erythropoietin in reducing the exposure to allogenic red blood cells in a large diverse group of critically ill patients.” More than four million patients are admitted to intensive care units each year1 and approximately 35 to 50 percent of all patients admitted to an intensive care unit (ICU) today receive on average five red blood cell (RBC) units during their stay.(2,3)
The multi-center, double-blind, placebo-controlled study enrolled 1,302 critically ill patients and assessed the efficacy of once-weekly (QW) dosing of PROCRIT 40,000 units compared to placebo in reducing the need for red blood cell (RBC) transfusions. The efficacy endpoint upon which the two treatments were compared was assessed by comparing the percent of patients in each treatment group who received any RBC transfusion between study days 1 and 28.
Patients were randomized to receive either PROCRIT (650 patients) or placebo (652 patients) by subcutaneous injection on intensive care unit (ICU) day three and continued weekly for patients who remained in the hospital, for a total of three doses (study days 1, 7 and 14). Patients who remained in the ICU on study day 21 received a fourth dose. Patients receiving PROCRIT were less likely to be transfused (60.4% placebo versus 50.5% PROCRIT p< .0004; odds ratio 0.67, 95% CI, 0.54, 0.83).
Secondary efficacy endpoints were cumulative RBC units transfused per patient through study day 28; cumulative mortality through study day 28; change in hemoglobin from baseline; and time to first transfusion or death. There was a 19% reduction in the total units of RBCs transfused in the PROCRIT group (1963 units placebo versus 1590 units PROCRIT, p < .001). The increase in hemoglobin from baseline to final was greater in the PROCRIT group (1.32 ± 2 g/dL versus .94 ± 1.9 g/dL, p < .001). Despite receiving fewer RBC transfusions, patients treated with PROCRIT achieved a higher hemoglobin level. Mortality (14% PROCRIT, 15% placebo) and adverse clinical events were comparable.
Anemia is a potentially life-threatening condition that occurs when the body lacks enough red blood cells to carry oxygen from the lungs to the tissues and organs throughout the body. Many critically ill patients experience impairment in the production of red bloods cells, which contributes to the development and persistence of their anemia. Critically ill patients may be suffering from conditions that make them more prone to anemia, such as cancer, chronic renal failure, or human immunodeficiency virus (HIV). Surgery or trauma may also predispose patients to develop anemia. Sometimes no precise cause for anemia can be found.(1)
PROCRIT stimulates red blood cell production and has a protein sequence identical to the body’s naturally occurring erythropoietin, which is produced in healthy kidneys.
PROCRIT has been used in more than one million people and is indicated for treatment of anemic chemotherapy-treated patients with nonmyeloid malignancies*, anemic chronic kidney disease patients**, anemic elective, noncardiac, nonvascular surgery patients***, and anemic zidovudine-treated, human immunodeficiency virus (HIV)-infected patients****. These patients may require treatment in the ICU for complications of their disease. Additionally, critically ill patients may experience a blunted erythropoietin response to anemia(4).
Oncology: PROCRIT is contraindicated in patients with uncontrolled hypertension. Hypertension, associated with rapid increases in HCT, has been rarely noted in cancer patients treated with PROCRIT. Nevertheless, blood pressure should be monitored carefully, particularly in patients with an underlying history of hypertension or cardiovascular disease. Consistent with patients’ chemotherapy and disease state, the most commonly reported side effects in PROCRIT trials were pyrexia, vomiting, shortness of breath, paresthesia, and upper respiratory infection. Only diarrhea and edema occurred with a statistically greater incidence in PROCRIT-treated patients than placebo-treated patients.
Nephrology: PROCRIT therapy is generally well tolerated. Rapid increases in HCT may be associated with hypertension and should be avoided. PROCRIT brand of Epoetin alfa is marketed for the treatment of anemia in chronic renal failure patients not on dialysis.
Immunology: Any adverse experiences associated with PROCRIT were believed to be related to the disease process of acquired immunodeficiency syndrome (AIDS), not to therapy with PROCRIT. Adverse experiences did not occur with clinically significant greater incidence than those seen in placebo-treated patients.
Surgery: In a placebo-controlled trial of patients scheduled for orthopedic surgery, the overall incidence of adverse events was similar in PROCRIT- and placebo-treated patients. The most commonly occurring adverse events were pyrexia, nausea, and constipation, which were not unexpected for patients undergoing surgery and receiving iron(5,6). The safety of the perioperative use of PROCRIT has been studied only in patients who received anticoagulant prophylaxis. The risk of postoperative thrombotic/vascular events cannot be excluded. In perioperative clinical trials, the overall incidence of thrombotic/vascular events was similar in Epoetin alfa- and placebo-treated patients with Hb > 10 to ? 13 g/dL.
For full U.S. Prescribing Information and additional information on PROCRIT and anemia, please refer to the enclosed full Prescribing Information or visit www.procrit.com.
Ortho Biotech Products, L.P., marketers of PROCRIT® (Epoetin alfa), was established in Raritan, NJ in 1990 as the first biotechnology subsidiary of Johnson & Johnson. Ortho Biotech is committed to seeking and developing improved treatment options with better outcomes for patients and health care professionals.
Editor’s Note: Go to jama.ama-assn.org for additional information.
1. Leapfrog Group, Founded by The Business Roundtable, November 2000 ICU Physician Staffing.
2. Vincent JL, Baron JF, Gattinoni L, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002; 288: 1499-1507.
3. Corwin HL, Abraham E, Fink MP, et al., Anemia and blood transfusion in the critically ill: current clinical practice in the US — The CRIT Study [abstract]., Critical Care Med. 2001;29(suppl):A2.
* For anemia due to the effect of chemotherapy.
** PROCRIT brand of Epoetin alfa is marketed for the treatment of anemia in chronic renal failure patients not on dialysis.
*** At high risk for perioperative transfusions (hemoglobin [Hb] >10 to ? 13 g/dL) due to significant, anticipated blood loss during elective, noncardiac, nonvascular surgery. PROCRIT is not indicated for anemic patients who are willing to donate autologous blood.
**** In patients with endogenous serum erythropoietin levels ? 500 mU/mL who are receiving ? 600 mg zidovudine daily.
4. Rogiers, P., Zhang, H., Leeman, M., et al. Erythropoietin response is blunted in critically ill patients. Intensive Care Med. 1997; 23:159-162.
5. De Andrade JR, Jove M, Landon G, Frei D, Guilfoyle M, Young DC. Am J Orthop. 1996;25:533-542.
6. Goldberg MA, McCutchen JW, Joive M, et al. Am J Orthop. 1996;25:433-552.