What side effects are associated with this type of intervention?

Common treatments for Iron-Deficiency Anemia include erythropoiesis-stimulating agents (ESAs) and iron supplementation. ESAs, such as darbepoetin, can cause side effects like hypertension, headache, and an increased risk of thrombotic events. Oral iron supplements often lead to gastrointestinal issues, including constipation, diarrhea, nausea, and abdominal pain. Intravenous iron can cause allergic reactions, hypotension, and, in rare cases, anaphylaxis. Both forms of iron supplementation can lead to iron overload if not monitored properly.

What prior FDA approvals exist?

The FDA has approved several treatments for Iron-Deficiency Anemia that involve erythropoiesis-stimulating agents (ESAs) and iron supplementation. Epoetin alfa and darbepoetin alfa are two ESAs that have been widely used to stimulate red blood cell production. These agents are often combined with iron supplements to enhance their efficacy. Intravenous iron formulations such as iron dextran, iron sucrose, and ferric carboxymaltose have been approved to treat iron deficiency, particularly in patients who cannot tolerate oral iron or have chronic kidney disease. The combination of ESAs with IV iron is similar to the approach being studied in the trial involving Darbepoetin plus IV Iron, aiming to reduce transfusions and maintain iron sufficiency.

What other types of research exist?

Promising novel alternatives to Darbepoetin plus IV Iron for Iron-Deficiency Anemia patients include: 1) Minibody agonists of the thrombopoietin receptor, which have shown potential in stimulating erythropoiesis. 2) Luspatercept, which is being investigated for its ability to enhance erythroid maturation and reduce transfusion dependence. 3) Anti-TNF agents like infliximab or etanercept, which have shown efficacy in certain anemias with inflammatory components. These alternatives are in various stages of clinical trials and may offer new options for patients in 2024.

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Erythropoiesis-Stimulating Agent

Darbe + IV Iron for Premature Infants (DIVI Trial)

Q: What is the mechanism of action of this treatment?

The most common treatments for Iron-Deficiency Anemia include erythropoiesis-stimulating agents (ESAs) and iron supplementation. ESAs, such as darbepoetin alfa, stimulate the bone marrow to produce more red blood cells, which helps increase hemoglobin levels and reduce the need for blood transfusions. Iron supplementation, especially intravenous forms like Ferumoxytol or low molecular weight iron dextran, provides the necessary iron for hemoglobin production in red blood cells. This combination ensures that the newly produced red blood cells are functional and effective in oxygen transport, addressing both the production and quality of red blood cells in iron-deficiency anemia patients.

Phase 2

Recruiting

Led By Sandra E Juul, MD, PhD

Research Sponsored by University of Washington

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

NICU patients (male and female) born at 24-0/7 to 31-6/7 weeks of gestation

Be younger than 18 years old

Must not have

Known fetal/infant anomalies of clinical significance (brain, cardiac, chromosomal anomalies)

Unable to consent in English or Spanish

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 1 and 2 years corrected age.

Awards & highlights

Summary

This trial uses Darbepoetin and slow-release IV iron to help preterm infants. The treatment aims to reduce the need for blood transfusions, keep iron levels stable, and support better brain development without causing stomach problems.

Who is the study for?

This trial is for preterm infants born between 24 and almost 32 weeks of gestation. It's open to all eligible NICU patients regardless of sex, race, or ethnicity. Infants with high iron levels, infections at enrollment, significant clinical anomalies, or whose parents cannot consent within 72 hours after birth are excluded.

What is being tested?

The study tests if Darbepoetin (Darbe) combined with IV iron (Ferumoxytol or low molecular weight iron dextran) can reduce the need for blood transfusions while maintaining sufficient iron levels and improving neurodevelopment in premature infants compared to oral iron supplements.

What are the potential side effects?

Potential side effects may include reactions at the injection site, gastrointestinal disturbances due to oral supplements versus IV treatment differences in tolerance, and possible alterations in gut microbiome.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My baby was born between 24 and 31 weeks of pregnancy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My baby has been diagnosed with a significant health condition.

Select...

I cannot give consent in English or Spanish.

Select...

I currently have a confirmed infection like sepsis or UTI.

Select...

I am a mother and under 18 years old.

Select...

My baby's parental consent was not obtained within 72 hours after birth.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 1 and 2 years corrected age.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 1 and 2 years corrected age.

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 1 and 2 years corrected age. for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Number of Blood transfusions

Number of IV iron doses required to maintain a ferritin level of > 75 ng/mL

Plasma Ferritin at 35-36 weeks PMA

+1 more

Secondary outcome measures

Early gut microbiome comparison between study groups

Hematocrit

Late gut microbiome comparison between study groups

+6 more

Side effects data

From 2017 Phase 4 trial • 2825 Patients • NCT00773513

31%

Hypertension

19%

Diarrhoea

16%

Procedural hypotension

15%

Muscle spasms

14%

Bronchitis

14%

Urinary tract infection

14%

Cough

12%

Pneumonia

12%

Nasopharyngitis

12%

Constipation

12%

Arteriovenous fistula site complication

11%

Back pain

11%

Hyperparathyroidism secondary

11%

Upper respiratory tract infection

10%

Vomiting

10%

Anaemia

10%

Hypotension

10%

Hyperkalaemia

10%

Hyperphosphataemia

Fluid overload

Headache

Atrial fibrillation

Pain in extremity

Arthralgia

Insomnia

Pruritus

Arteriovenous fistula thrombosis

Dyspnoea

Osteoarthritis

Gastroenteritis

Nausea

Pyrexia

Dyspepsia

Dizziness

Abdominal pain

Sepsis

Influenza

Musculoskeletal pain

Oedema due to renal disease

Acute myocardial infarction

Oedema peripheral

Depression

Cataract

Abdominal pain upper

Respiratory tract infection

Epistaxis

Asthenia

Myocardial infarction

Lower respiratory tract infection

Peritonitis

Septic shock

Cardiac arrest

Angina pectoris

Syncope

Cardiac failure

Acute coronary syndrome

Cardiac failure congestive

Sudden death

Device related sepsis

Cellulitis

Gastrointestinal haemorrhage

Device related infection

Coronary artery disease

Femur fracture

Peripheral ischaemia

Peripheral arterial occlusive disease

Ischaemic stroke

Cerebrovascular accident

Death

Pleural effusion

Non-cardiogenic pulmonary oedema

End stage renal disease

Seizure

Staphylococcal bacteraemia

Myocardial ischaemia

Femoral neck fracture

Non-cardiac chest pain

Cardio-respiratory arrest

Cardiogenic shock

Angina unstable

Atrial flutter

Arteriovenous graft thrombosis

Arteriovenous fistula aneurysm

Subdural haematoma

Gastric ulcer haemorrhage

Intestinal ischaemia

Intestinal obstruction

Colitis

Pancreatitis acute

Hypertensive crisis

Deep vein thrombosis

General physical health deterioration

Chest pain

Gangrene

Staphylococcal sepsis

Bacteraemia

Arteriovenous fistula site infection

Catheter site infection

Cholecystitis

Cholecystitis acute

Arthritis bacterial

Lung infection

Hip fracture

Pelvic fracture

Peripheral artery stenosis

Confusional state

Infected skin ulcer

Diverticulitis

Erysipelas

Endocarditis

Peripheral vascular disorder

Aortic stenosis

Post procedural haemorrhage

Rib fracture

Head injury

Large intestine polyp

Rectal haemorrhage

Gastritis

Hypoglycaemia

Cachexia

Hyperglycaemia

Diabetic foot infection

Postoperative wound infection

Bradycardia

Aortic valve stenosis

Arteriovenous fistula site haemorrhage

Fall

Extremity necrosis

Transient ischaemic attack

Pulmonary oedema

Acute pulmonary oedema

Chronic obstructive pulmonary disease

Pneumonia aspiration

Pulmonary embolism

Renal impairment

Skin ulcer

Diabetic foot

Urosepsis

100%

80%

60%

40%

20%

Study treatment Arm

Erythropoiesis Stimulating Agents

Methoxy Polyethylene Glycol-Epoetin Beta

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Group 5Experimental Treatment2 Interventions

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive FMX: 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Group II: Group 4Experimental Treatment2 Interventions

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive FMX: 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Group III: Group 3Experimental Treatment2 Interventions

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive LMW-ID: 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Group IV: Group 2Experimental Treatment2 Interventions

Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive LMW-ID: 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L

Group V: Group 1. Oral ironActive Control1 Intervention

Oral iron is started on day 7 of life if baby is feeding 100 mL/kg/day. Iron supplements of up to 12 mg/kg/day are given based on CBC, retic, ret-hgb, serum ferritin and zinc protoporphyrin to heme ratio (ZnPP/H). Iron supplements are adjusted every 2 weeks following iron studies.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Darbepoetin alfa

FDA approved

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Iron-Deficiency Anemia include erythropoiesis-stimulating agents (ESAs) and iron supplementation. ESAs, such as darbepoetin alfa, stimulate the bone marrow to produce more red blood cells, which helps increase hemoglobin levels and reduce the need for blood transfusions. Iron supplementation, especially intravenous forms like Ferumoxytol or low molecular weight iron dextran, provides the necessary iron for hemoglobin production in red blood cells. This combination ensures that the newly produced red blood cells are functional and effective in oxygen transport, addressing both the production and quality of red blood cells in iron-deficiency anemia patients.

Distinguishing anemia and iron deficiency of heart failure: signal for severity of disease or unmet therapeutic need?