A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD

Robert Toto; Jeffrey Petersen; Jeffrey S. Berns; Eldrin Foster Lewis; Qui Tran; Matthew R. Weir

doi:10.1681/ASN.2020050556

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Significance Statement

Erythropoietin-stimulating agents (ESAs) have historically been titrated to achieve a predefined hemoglobin concentration when treating patients with CKD and anemia. It is unknown whether an alternative dosing strategy might reduce the need for red blood cell transfusions, mitigate potential factors contributing to increased cardiovascular risk associated with use of high ESA doses, and decrease cumulative dose exposure. This randomized trial was designed to describe the benefits and potential risks of a new treatment strategy, using a low fixed dose of darbepoetin alfa compared with a hemoglobin-based, titration-dose algorithm. The authors show that use of a low fixed dose of darbepoetin may be an alternative to a dose-titration approach to minimize red blood cell transfusions in patients with CKD and anemia, and may result in a smaller cumulative dose.

Abstract

Background Exposure to high doses or a high cumulative dose of erythropoiesis-stimulating agents (ESAs) may contribute to cardiovascular events in patients with CKD and anemia. Whether using a low fixed ESA dose versus dosing based on a hemoglobin-based, titration-dose algorithm in such patients might reduce risks associated with high ESA doses and decrease the cumulative exposure—while reducing the need for red blood cell transfusions—is unknown.

Methods In this phase-3, randomized trial involving 756 adults with stage-3 to -5 CKD and anemia, we evaluated incidence of red blood cell transfusions for participants randomized to receive darbepoetin given as a fixed dose (0.45 µg/kg every 4 weeks) versus administered according to a hemoglobin-based, titration-dose algorithm, for up to 2 years. Participants received transfusions as deemed necessary by the treating physician.

Results There were 379 patients randomized to the fixed-dose group, and 377 to the titration-dose group. The percentage of participants transfused did not differ (24.1% and 24.4% for the fixed-dose and titration-dose group, respectively), with similar time to first transfusion. The titration-dose group achieved significantly higher median hemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl). The fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 µg) compared with the titration-dose group (53.6 µg median monthly dose). The FD and TD group received a median (Q1, Q3) cumulative dose per 4 weeks of darbepoetin of 30.9 (21.8, 40.0) µg and 53.6 (31.1, 89.9) µg, respectively; the median of the difference between treatment groups was −22.1 (95% CI, −26.1 to −18.1) µg.

Conclusions These findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing.

View Full Text

Log in through your institution

Purchase access

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$32.00

You will have access to the article for 24 hours.

If you do not have an account, you will need to create one and you will be asked for your name, email address and other information. Just like commercial web sites, we do need details from you in order to complete your purchase of an article. Select the "Create an Account" link to create your account.

You will then be asked to register a user name, email address and you will need to create a password that is at least eight characters in length. As you move through the registration page, you will have to verify you are a person by completing a Captcha request. Lastly, your first and last name will be required.

Once your information is successfully saved, the system will redisplay the home page of the journal. From there, navigate back to the article to purchase. Select the article and at the bottom of the page, use the credentials you just created to login. The article will be added to your shopping cart. You can continue to navigate across JASN and CJASN adding to your cart from both journals. When you are ready to complete your purchse, select the Shopping Cart from the upper right hand corner of the page and follow the onscreen instructions.