Darbepoetin Administration to Preterm Infants

2014-08-27 03:44:15 | BioPortfolio


Infants born prematurely do not increase production of the primary red cell growth factor, erythropoietin (Epo), and often develop an anemia called the "anemia of prematurity." The anemia of prematurity is the most common anemia seen in neonates, and is due to a failure of Epo production. Human recombinant Epo (rHuEpo), given three to five times a week, is successful in treating the anemia of prematurity. A slightly modified, long-acting version of rHuEpo, called darbepoetin alfa (darbepoetin), is now available and has proven effective in increasing hematocrit (red blood cell levels) in adults. In addition to its red cell stimulating properties, recent evidence has shown that rHuEpo is protective in the developing or injured brain. We have designed a randomized, masked, placebo-controlled study to determine the safety and short and long term efficacy of darbepoetin. At this time, darbepoetin has been studied primarily in adults and pediatric patients, but there is evidence from pilot studies that darbepoetin would be useful in the neonatal setting as well. It also may well improve neurodevelopmental outcomes in preterm neonates. We hypothesize that: 1. The administration of darbepoetin to preterm infants 500 to 1,250 grams birth weight will result in increased reticulocyte counts and decreased transfusions compared to placebo; and 2. The administration of darbepoetin will be associated with an increased mental developmental index at 18-22 months compared to placebo.


A novel erythropoiesis stimulating protein, Darbepoetin alfa (Darbepoetin) has been developed by Amgen Inc. and has been shown to be effective in increasing hematocrit using once weekly or once every other week dosing in adults with anemia due to end stage renal disease or cancer. However, it is presently being evaluated for use in children with hyporegenerative anemias, and has not yet been evaluated for use in infants with anemia of prematurity. Preterm infants respond to human recombinant erythropoietin (Epo) by increasing reticulocytes, yet the multiple subcutaneous doses diminish its routine use in the NICU. With the possibility of once a week or once every other week dosing, the use of Darbepoetin in this population appears promising. While it is likely that the use of red cell growth factors such as rHuEpo or darbepoetin will not eliminate the need for all erythrocyte transfusions in all infants, it is reasonable to postulate that the use of darbepoetin will eliminate the need for transfusion in some preterm infants, and reduce the need in others. European studies evaluating rHuEpo in preterm infants have successfully decreased donor exposure to 1 per patient. Our goal is to achieve similar success, which we define as a donor exposure of ≤1 donor per infant in clinical practice. This can be achieved through the use of red cell growth factors, judicious use of blood work for monitoring, and stringent transfusion guidelines. By decreasing total transfusions to <4 per infant, we can achieve this goal of ≤1 donor exposure per infant.

There will remain a population of extremely small, extremely ill infants in whom phlebotomy losses exceed the capacity to increase red cell mass through the use of Epo. Some investigators believe a combination of single donor erythrocyte transfusions and recombinant erythropoietin can serve to maintain an adequate circulating erythrocyte volume. A reasonable algorithm can be developed to assist in these determinations only through continued research. Continued critical evaluation of transfusion criteria, outcomes, new technologies limiting phlebotomy loss, and novel biologic and pharmacologic treatments can only serve to improve the care of ELBW infants who are highest risk for repeated transfusions. Our research aim is to study the safety and efficacy of darbepoetin in preterm infants in order to improve the outcomes of preterm infants by significantly decreasing the number of transfusions. Moreover, improving neurodevelopmental outcomes for preterm infants continues to be a goal for neonatal care providers that might begin to be approached through darbepoetin therapy. This study differs from previous erythropoietin studies in the following ways:

1. Darbepoetin will be compared to placebo and to rHuEpo, allowing two thirds of the patients to receive some form of red cell growth factor, and allowing SC dosing to occur once a week in the darbepoetin recipients compared with the usual three times a week SC dosing in the rHuEpo recipients (those in the placebo group will not receive sham injections)

2. Dosing will begin 1-2 days earlier on average than in any previously published study

3. Transfusion guidelines are the most rigorous applied to date, and will be used at sites that are all at altitudes > 4,000 feet

4. A target Epo concentration of >500 mU/mL in the treatment group is proposed in order to evaluate neurodevelopmental differences between groups, and the study is powered to determine a difference between treatment groups and placebo

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Infant, Newborn


darbepoetin alfa, erythropoietin, sham injection


University of Colorado
United States


Active, not recruiting


University of New Mexico

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:44:15-0400

Clinical Trials [2420 Associated Clinical Trials listed on BioPortfolio]

Study of the Efficacy of Darbepoetin Alfa in the Treatment of Renal Anemia

Anaemia is a common consequence of chronic renal failure. Darbepoetin alfa is a unique erythropoietic protein that stimulates erythropoiesis by the same mechanism as endogenous erythropiet...

Chemotherapy Related Anemia

This study is investigating darbepoetin alfa for the treatment of anemia in patients with non-myeloid cancers who are receiving chemotherapy. Darbepoetin alfa is a recombinant protein tha...

A Study of Darbepoetin Alfa in Patients With Myelodysplastic Syndrome (MDS)

The primary objectives of the trial are to assess erythroid response to darbepoetin alfa, as determined by changes in hemoglobin and/or red blood cell (RBC) transfusion-dependence and to d...

Phase 2 Study of Darbepoetin Alfa Extended Dosing

Multicenter, open label single arm study in which 140 subjects with CRI who are currently receiving SC darbepoetin alfa once every other week will receive darbepoetin alfa once every 4 wee...

A Study of Darbepoetin Alfa for the Treatment of Anemia in Subjects With Non-Myeloid Malignancy Receiving Multicycle Chemotherapy

The purpose of this study is to evaluate the efficacy of darbepoetin alfa as 500ug once every 3 weeks to show that the dose and schedule are not inferior to darbepoetin alfa administered a...

PubMed Articles [3910 Associated PubMed Articles listed on BioPortfolio]

Involvement of prolactin in newborn infant irritability following maternal perinatal anxiety symptoms.

Newborn irritability could be an unique and special status and/or adverse neurobehavioral outcomes which was independent of serious disease. To determine whether maternal perinatal anxiety symptoms wa...

The midwife as a guide for the application of the Kangaroo mother care method. A case report.

We present a clinical case of a premature birth from a mother of 33+5 weeks gestation where the newborn was admitted to the neonatal unit due to her low weight, chest retraction and prematurity, despi...

Toward a solution for cardiac failure in the newborn.

The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transp...

Protective effects of Tadalafil and darbepoetin against ischemia - reperfusion injury in a rat testicular torsion model.

To evaluate protective effects of darbepoetin and tadalafil against ischemiareperfusion injury in ipsilateral and contralateral testicle.

Comparing Therapeutic Efficacy and Safety of Epoetin Beta and Epoetin Alfa in the Treatment of Anemia in End-Stage Renal Disease Hemodialysis Patients.

Anemia is one of the most prevalent complications in patients with chronic kidney disease, which is believed to be caused by the insufficient synthesis of erythropoietin by the kidney. This phase III ...

Medical and Biotech [MESH] Definitions

This recombinant erythropoietin, a 165-amino acid glycoprotein (about 62% protein and 38% carbohydrate), regulates red blood cell production. Epoetin alfa is produced by Chinese hamster ovary cells into which the human erythropoietin gene has been inserted. (USP Dictionary of USAN and International Drug Names, 1996).

A recombinant protein which stimulates ERYTHROPOIESIS used to treat ANEMIA.

The event that a FETUS is born alive with heartbeats or RESPIRATION regardless of GESTATIONAL AGE. Such liveborn is called a newborn infant (INFANT, NEWBORN).

An infant during the first month after birth.

A syndrome of persistent PULMONARY HYPERTENSION in the newborn infant (INFANT, NEWBORN) without demonstrable HEART DISEASES. This neonatal condition can be caused by severe pulmonary vasoconstriction (reactive type), hypertrophy of pulmonary arterial muscle (hypertrophic type), or abnormally developed pulmonary arterioles (hypoplastic type). The newborn patient exhibits CYANOSIS and ACIDOSIS due to the persistence of fetal circulatory pattern of right-to-left shunting of blood through a patent ductus arteriosus (DUCTUS ARTERIOSUS, PATENT) and at times a patent foramen ovale (FORAMEN OVALE, PATENT).

More From BioPortfolio on "Darbepoetin Administration to Preterm Infants"

Quick Search


Relevant Topic

Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Searches Linking to this Trial