Pilot Trial Investigating Every Other Day Dosing of Oral Iron in Premature Infants (IQONic)

NCT ID: NCT06555315

Last Updated: 2024-08-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-01

Study Completion Date

2026-03-28

Brief Summary

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Study focuses on determining if daily versus every-other-day (EOD) oral iron at the same dose per kilogram per day will achieve similar incidence of iron replete status at 36 weeks post-menstrual age in premature neonates

Detailed Description

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Iron is an important component of hemoglobin, and an essential part of erythropoiesis. It is also a necessary micronutrient for rapidly proliferating and differentiating cells and tissues especially in the brain. Iron deficiency in infancy has been associated with anemia and impaired neurodevelopmental outcomes that extend into childhood. Premature infants are at highest risk for iron deficiency because they are deprived of the iron accretion that occurs in the third trimester of pregnancy, are born with lower iron stores compared to their term counterparts, and have increased utilization and depletion of iron stores with their rapid growth rate.

In older populations, EOD iron supplementation is as effective as daily iron supplementation in the treatment of iron deficiency anemia, with studies revealing significantly fewer gastrointestinal side effects in those who are on EOD iron. Adults regulate their iron status through a feedback pathway involving hepcidin whereby iron-sufficient individuals will have upregulated hepcidin, which leads to decreased iron absorption and availability. Recent studies have revealed that pediatric patients and premature neonates regulate iron absorption through hepcidin in a similar fashion. Though the regulation of iron status through hepcidin has been studied in extremely premature neonates, the clinical effect of EOD dosing of iron has not yet been examined in this population.

This is a non-inferiority, blinded, randomized control trial designed to investigate if EOD iron is comparable to daily iron dosing in achieving iron replete status by reticulocyte hemoglobin measurements in premature infants.

Conditions

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Very Low Birth Weight Infant Premature Infants Anemia of Prematurity Iron Deficiency, Anaemia in Children Extremely Low Birth Weight

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Outcome Assessors
A statistician who is blinded to the study allocation will analyze the data.

Study Groups

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Control Group

After the infant achieves full enteral feeds, the infant is started on 6 mg/kg of oral iron daily supplementation. The dose of 6 mg/kg of enteral iron was chosen based on the aforementioned recommendations with evidence of its safety, while minimizing the need to increase the enteral iron dosage if an infant were to be started on ESAs where a dose of 6 mg/kg of enteral iron supplementation is the standard practice. Phlebotomy to obtain a complete blood count, reticulocyte count, and reticulocyte hemoglobin count is pursued the Monday after starting iron supplementation and every 2 weeks thereafter to weeks to monitor hematocrit or hemoglobin levels and iron status.

Group Type OTHER

6 mg/kg of oral iron as ferrous sulfate administered every day.

Intervention Type DIETARY_SUPPLEMENT

6 mg/kg of oral iron as daily ferrous sulfate instead of 6mg/kg of oral iron supplementation administered every other day.

Intervention Group

After the infant achieves full enteral feeds, the infant is started on 6mg/kg of oral iron supplementation administered every other day. The dose of 6 mg/kg of enteral iron was chosen based on the aforementioned recommendations with evidence of its safety, while minimizing the need to increase the enteral iron dosage if an infant were to be started on ESAs where a dose of 6 mg/kg of enteral iron supplementation is the standard practice. Phlebotomy to obtain a complete blood count, reticulocyte count, and reticulocyte hemoglobin count is pursued the Monday after starting iron supplementation and every 2 weeks thereafter to weeks to monitor hematocrit or hemoglobin levels and iron status.

Group Type EXPERIMENTAL

6 mg/kg of oral iron as ferrous sulfate administered every other day.

Intervention Type DIETARY_SUPPLEMENT

6mg/kg of oral iron as ferrous sulfate administered every other day instead of 6 mg/kg of oral iron daily supplementation.

Interventions

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6 mg/kg of oral iron as ferrous sulfate administered every other day.

6mg/kg of oral iron as ferrous sulfate administered every other day instead of 6 mg/kg of oral iron daily supplementation.

Intervention Type DIETARY_SUPPLEMENT

6 mg/kg of oral iron as ferrous sulfate administered every day.

6 mg/kg of oral iron as daily ferrous sulfate instead of 6mg/kg of oral iron supplementation administered every other day.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Children (Minor \< 18 years of age)
* Neonates
* Hospitalized
* Premature infants who are on full enteral feeds and are started on oral iron
* Premature infants who completed 26 0/7 to 32 6/7 weeks' gestation at birth

Exclusion Criteria

• Infants with known congenital anomalies or chromosomal abnormalities (such as Trisomy 18 or Trisomy 21), conditions that affect iron metabolism (such as thalassemia or hemochromatosis), bleeding disorders or coagulopathy, and received iron parenterally prior to randomization
Minimum Eligible Age

26 Weeks

Maximum Eligible Age

32 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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CHRISTUS Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pratik K Parikh, MD

Role: PRINCIPAL_INVESTIGATOR

CHRISTUS Health

Richelle L Homo, MD

Role: PRINCIPAL_INVESTIGATOR

CHRISTUS Health; Brooke Army Medical Center

Locations

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CHRISTUS Children's

San Antonio, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rosario Ocampo

Role: CONTACT

210-704-4996

Donna Rodney

Role: CONTACT

(210) 683-7746

Facility Contacts

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Rosario Ocampo

Role: primary

210-639-3157

References

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Sriranjan J, Kalata C, Fusch G, Thomas K, Goswami I. Prevalence and Implications of Low Reticulocyte-Hemoglobin Levels among Extreme Preterm Neonates: A Single-Center Retrospective Study. Nutrients. 2022 Dec 16;14(24):5343. doi: 10.3390/nu14245343.

Reference Type RESULT
PMID: 36558502 (View on PubMed)

Wang Y, Wu Y, Li T, Wang X, Zhu C. Iron Metabolism and Brain Development in Premature Infants. Front Physiol. 2019 Apr 25;10:463. doi: 10.3389/fphys.2019.00463. eCollection 2019.

Reference Type RESULT
PMID: 31105583 (View on PubMed)

McCarthy EK, Dempsey EM, Kiely ME. Iron supplementation in preterm and low-birth-weight infants: a systematic review of intervention studies. Nutr Rev. 2019 Dec 1;77(12):865-877. doi: 10.1093/nutrit/nuz051.

Reference Type RESULT
PMID: 31532494 (View on PubMed)

Nii M, Okamoto T, Sugiyama T, Aoyama A, Nagaya K. Reticulocyte hemoglobin content changes after treatment of anemia of prematurity. Pediatr Int. 2022 Jan;64(1):e15330. doi: 10.1111/ped.15330.

Reference Type RESULT
PMID: 36321339 (View on PubMed)

Puia-Dumitrescu M, Tanaka DT, Spears TG, Daniel CJ, Kumar KR, Athavale K, Juul SE, Smith PB. Patterns of phlebotomy blood loss and transfusions in extremely low birth weight infants. J Perinatol. 2019 Dec;39(12):1670-1675. doi: 10.1038/s41372-019-0515-6. Epub 2019 Oct 3.

Reference Type RESULT
PMID: 31582812 (View on PubMed)

Bahr TM, Tan S, Smith E, Beauman SS, Schibler KR, Grisby CA, Lowe JR, Bell EF, Laptook AR, Shankaran S, Carlton DP, Rau C, Baserga MC, Flibotte J, Zaterka-Baxter K, Walsh MC, Das A, Christensen RD, Ohls RK; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Serum ferritin values in neonates <29 weeks' gestation are highly variable and do not correlate with reticulocyte hemoglobin content. J Perinatol. 2023 Nov;43(11):1368-1373. doi: 10.1038/s41372-023-01751-z. Epub 2023 Aug 18.

Reference Type RESULT
PMID: 37596391 (View on PubMed)

Karakoc G, Orgul G, Sahin D, Yucel A. Is every other day iron supplementation effective for the treatment of the iron deficiency anemia in pregnancy? J Matern Fetal Neonatal Med. 2022 Mar;35(5):832-836. doi: 10.1080/14767058.2021.1910666. Epub 2021 Apr 18.

Reference Type RESULT
PMID: 33866933 (View on PubMed)

Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020 May;105(5):1232-1239. doi: 10.3324/haematol.2019.220830. Epub 2019 Aug 14.

Reference Type RESULT
PMID: 31413088 (View on PubMed)

von Siebenthal HK, Gessler S, Vallelian F, Steinwendner J, Kuenzi UM, Moretti D, Zimmermann MB, Stoffel NU. Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study. EClinicalMedicine. 2023 Nov 3;65:102286. doi: 10.1016/j.eclinm.2023.102286. eCollection 2023 Nov.

Reference Type RESULT
PMID: 38021373 (View on PubMed)

Pasupathy E, Kandasamy R, Thomas K, Basheer A. Alternate day versus daily oral iron for treatment of iron deficiency anemia: a randomized controlled trial. Sci Rep. 2023 Feb 1;13(1):1818. doi: 10.1038/s41598-023-29034-9.

Reference Type RESULT
PMID: 36725875 (View on PubMed)

German KR, Comstock BA, Parikh P, Whittington D, Mayock DE, Heagerty PJ, Bahr TM, Juul SE. Do Extremely Low Gestational Age Neonates Regulate Iron Absorption via Hepcidin? J Pediatr. 2022 Feb;241:62-67.e1. doi: 10.1016/j.jpeds.2021.09.059. Epub 2021 Oct 7.

Reference Type RESULT
PMID: 34626672 (View on PubMed)

Uyoga MA, Mikulic N, Paganini D, Mwasi E, Stoffel NU, Zeder C, Karanja S, Zimmermann MB. The effect of iron dosing schedules on plasma hepcidin and iron absorption in Kenyan infants. Am J Clin Nutr. 2020 Oct 1;112(4):1132-1141. doi: 10.1093/ajcn/nqaa174.

Reference Type RESULT
PMID: 32678434 (View on PubMed)

Manapurath RM, Gadapani Pathak B, Sinha B, Upadhyay RP, Choudhary TS, Chandola TR, Mazumdar S, Taneja S, Bhandari N, Chowdhury R. Enteral Iron Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis. Pediatrics. 2022 Aug 1;150(Suppl 1):e2022057092I. doi: 10.1542/peds.2022-057092I.

Reference Type RESULT
PMID: 35921671 (View on PubMed)

MacQueen BC, Baer VL, Scott DM, Ling CY, O'Brien EA, Boyer C, Henry E, Fleming RE, Christensen RD. Iron Supplements for Infants at Risk for Iron Deficiency. Glob Pediatr Health. 2017 Apr 25;4:2333794X17703836. doi: 10.1177/2333794X17703836. eCollection 2017.

Reference Type RESULT
PMID: 28491927 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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2024-091

Identifier Type: -

Identifier Source: org_study_id

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