Results from Study Evaluating Procrit in Intensive Care Unit Patients Published in New England Journal of Medicine

BRIDGEWATER, N.J., September 05, 2007 /PRNewswire/ -- Results from an investigational study researching the use of PROCRIT(R) (Epoetin alfa) in medical, surgical and trauma patients admitted to an intensive care unit (ICU) were published in today's New England Journal of Medicine. 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.

Study Design

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.

Study Findings

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.

    Important U.S. Safety Information for PROCRIT


    From the Boxed Warnings

    -- Use the lowest dose of PROCRIT that will gradually increase the

       hemoglobin (Hb) concentration to the lowest level sufficient to avoid

       the need for red blood cell (RBC) transfusion.


    -- PROCRIT and other erythropoiesis-stimulating agents (ESAs) increased

       the risk for death and for serious cardiovascular events (including

       serious arterial and venous thromboembolic events, myocardial

       infarction, stroke, congestive heart failure) when administered to

       target a Hb of greater than 12 g/dL. A rate of hemoglobin rise of

       greater than 1 g/dL over 2 weeks may also contribute to these risks.


    -- Cancer patients: Use of ESAs:

      -- Shortened the time to tumor progression in patients with advanced

         head and neck cancer receiving radiation therapy when administered to

         target a Hb of greater than 12 g/dL.


      -- Shortened overall survival and increased deaths attributed to disease

         progression at 4 months in patients with metastatic breast cancer

         receiving chemotherapy when administered to target a Hb of greater

         than 12 g/dL.


      -- Increased the risk of death when administered to target a Hb of 12

         g/dL in patients with active malignant disease receiving neither

         chemotherapy nor radiation therapy. ESAs are not indicated for this

         population.


    -- Patients receiving PROCRIT pre-operatively for reduction of allogeneic

       RBC transfusions: A higher incidence of deep venous thrombosis was

       documented in patients receiving PROCRIT who were not receiving

       prophylactic anticoagulation.  Antithrombotic prophylaxis should be

       strongly considered when PROCRIT is used to reduce allogeneic RBC

       transfusions.

Contraindications

PROCRIT is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.

    Additional Important Safety Information

    -- Monitor Hb regularly during therapy, more frequently following a dosage

       adjustment or until Hb becomes stable.


    -- Cases of pure red cell aplasia (PRCA) and of severe anemia, with or

       without other cytopenias, associated with neutralizing antibodies to

       erythropoietin have been reported in patients with chronic renal

       failure receiving PROCRIT by subcutaneous administration.  If any

       patient develops a sudden loss of response to PROCRIT, accompanied by

       severe anemia and low reticulocyte count, and anti-erythropoietin

       antibody-associated anemia is suspected, withhold PROCRIT and other

       erythropoietic proteins.  Contact ORTHO BIOTECH (1-888-2ASKOBI or 1-

       888-227-5624) to perform assays for binding and neutralizing

       antibodies.  If erythropoietin antibody-mediated anemia is confirmed,

       PROCRIT should be permanently discontinued and patients should not be

       switched to other erythropoietic proteins.


    -- The safety and efficacy of PROCRIT therapy have not been established in

       patients with a known history of a seizure disorder or underlying

       hematologic disease (eg, sickle cell anemia, myelodysplastic syndromes,

       or hypercoagulable disorders).


    -- In some female patients, menses have resumed following PROCRIT therapy;

       the possibility of pregnancy should be discussed and the need for

       contraception evaluated.


    -- Prior to and regularly during PROCRIT therapy monitor iron status;

       transferrin saturation should be greater than or equal to 20% and

       ferritin should be greater than or equal to 100 ng/mL.  During therapy

       absolute or functional iron deficiency may develop and all patients

       will eventually require supplemental iron to adequately support

       erythropoiesis stimulated by PROCRIT.


    -- In studies, the most common side effects included fever (pyrexia),

       diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or

       loss of strength or weakness (asthenia, fatigue), shortness of breath,

       high blood pressure, headache, joint pain (arthralgias), abnormal skin

       sensations (as tingling or tickling or itching or burning;

       paresthesia), rash, constipation, and upper respiratory infection.

Please visit www.procrit.com for the full Prescribing Information, including the Boxed Warning.

About Johnson & Johnson Pharmaceutical Research & Development. L.L.C.

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) is part of Johnson & Johnson, the world's most broad-based producer of healthcare products. J&JPRD is headquartered in Raritan, New Jersey (USA), and has facilities throughout Europe and the United States. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic areas to address unmet medical needs worldwide.

About Ortho Biotech Products, L.P.

Ortho Biotech Products, L.P. is a leading biopharmaceutical company devoted to helping improve the lives of patients with cancer and with anemia due to multiple causes, including chronic kidney disease. Since it was founded in 1990, Ortho Biotech and its worldwide affiliates have earned a global reputation for researching, manufacturing and marketing innovative products that enhance patients' health. Located in Bridgewater, N.J., Ortho Biotech is an established market leader in Epoetin alfa therapy for anemia management. The company also markets treatments for recurrent ovarian cancer, rejection of transplanted organs and other serious illnesses. For more information, visit www.orthobiotech.com.

CONTACT: Stephanie Fagan, +1-908-541-4029, office, +1-201-572-9581, cell,or sfagan@obius.jnj.com

Web site: http://www.procrit.com/http://www.orthobiotech.com/

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Posted: September 2007

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