Clinical Trial: Optimized Erythropoietin (EPO) Treatment

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Optimized EPO Treatment of Neonatal Anemia

Brief Summary:

Neonatal anemia is the most commonly encountered hematologic problem among all neonates cared for in the neonatal intensive care unit (NICU). This project seeks to better understand the pathophysiology and treatment of this challenging and important condition, especially as it affects premature, critically ill very low birth weight (VLBW) infants who require intensive laboratory blood monitoring leading to the need for multiple red blood cell (RBC) transfusions (RBCTX). In the research strategy proposed in Study 1, Aims 1, 2 and 3, recombinant human erythropoietin (Epoetin Alpha, PROCRIT, provided by Janssen Scientific Affairs) will first be administered to 1.0 to 1.5 kg VLBW infants; then comprehensive pharmacokinetics (PK) and pharmacodynamics (PD) data will be systematically gathered and analyzed to identify clinical and laboratory covariate parameters differentiating the infants based on their level of Epoetin Alpha responsiveness. Finally the Epoetin Alpha responsiveness predictors thus determined will be applied prospectively in the Aim 4 Study, a 2 x 2 design in which VLBW infants will be identified as good or poor Epoetin Alpha responders, based on the predictors, and then randomly assigned to receive Epoetin Alpha treatment or no treatment. This will test the central hypothesis: RBCTX can be eliminated in the majority of good Epoetin Alpha responders by optimal administration of Epoetin Alpha, but only marginal reductions in RBCTx will occur in the poor Epoetin Alpha responders. This project challenges the prevailing thinking that the efficacy of Epoetin Alpha dosing in stimulating erythropoiesis is insufficient to eliminate the need for RBC transfusions in VLBW infants. Based on extensive preclinical and clinical PK/PD studies by our PPG team, we contend that previous Erythropoietin treatment studies in VLBW infants were not able to realize the full potential of Erythropoietin to eliminate RBCTX (in contrast to

Detailed Summary:

SPECIFIC AIMS Erythropoietin (Epo) stimulates red blood cell (RBC) production. Erythropoietin treatment of anemic, very low birth weight (VLBW) preterm infants has not been as effective as originally anticipated in eliminating multiple RBC transfusions (RBCTX). This conclusion is based on Epoetin Alpha dosing studies employing inconsistent RBCTX criteria, and study designs that did not fully consider Epoetin Alpha's complex pharmacokinetics (PK) and pharmacodynamics (PD). The hypothesis of this project challenges the conclusion that Epoetin Alpha therapy cannot reduce RBCTX in VLBW infants to a clinically important extent. This challenge is based on our novel comprehensive determinations of the PD of endogenous Epo in VLBW infants, and on our recent computer Epo simulation modeling results predicting that RBCTX can be eliminated in a select group of VLBW infants.

Study Objective To develop a pharmacodynamically-based, individualized medicine approach capable of completely eliminating RBCTX in an identifiable group of VLBW infants by optimally administering Epoetin Alpha.

Central Hypotheses Infants with good Epoetin Alpha responsiveness can be identified by a mechanism-driven, individualized prediction model. Optimized Epoetin Alpha treatment of the predicted good responders that is based on sound, evidence based PK/PD principles will eliminate the need for RBCTX.

Epoetin Alpha responsiveness is determined by two key components: 1) RBC production, which depends on Epoetin Alpha PD. 2) RBC lifespan. Individualized covariate-based (ie, patient specific characteristics) prediction of these two components is critical for the development of an individualized prediction model of Epoetin Alpha responsiveness that will be used for testing the Central Hypothesis. These important pred
Sponsor: University of Iowa

Current Primary Outcome: Number of red blood cell transfusions [ Time Frame: From date of randomization through day of life 28 or death, whichever comes first ]

The count of the number of packed red blood cell transfusions an infant receives during the entire course of their initial hospital stay.


Original Primary Outcome: Same as current

Current Secondary Outcome: Survival of Fetal Red Blood Cells in number of days [ Time Frame: From date of transfusion of biotinylated red blood cells until biotinylated red blood cells are no longer detectable in leftover blood samples, or death, whichever comes first. An expected average of 80-120 days. Assessed up to 5 months. ]

The count of the number of days that biotinylated red blood cells are identified in leftover blood samples. Counted from the day of transfusion until they are no longer able to be identified.


Original Secondary Outcome: Same as current

Information By: University of Iowa

Dates:
Date Received: May 30, 2013
Date Started: June 2014
Date Completion: June 2018
Last Updated: November 9, 2016
Last Verified: November 2016