Effectiveness of Nontraditional Hydroxyurea Algorithms: Novel and Clinical Evaluations (ENHANCE)

NCT07177300 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: ENHANCEGCF_Quinn
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The main reason for this research study is to learn more about hydroxyurea and the treatment of sickle cell anemia (SCA). Hydroxyurea is a medication that has been studied for many years and has been shown to provide benefits for people with SCA. In this research study, the investigators hope to learn more about how to improve the dosing and monitoring of hydroxyurea and learn more about the long-term effects of hydroxyurea over time. Hydroxyurea is usually dosed based only on your weight. Our study will use a new way to select a starting dose that is based on how each patient absorbs hydroxyurea.

Conditions

Sickle Cell Anemia (HbSS); Sickle-β0-thalassemia (HbSβ0)

Keywords

sickle cell anemia; SCD; sickle cell; hydroxyurea

Outcome Measures

Primary Outcomes (1)

• Composite Organ Injury

  Evidence of injury in any of four critical organ systems: brain, kidney, heart, or spleen. Participants will be classified as having met the composite endpoint if they fulfill at least one of the organ-specific criteria listed: cerebral infarction (silent or overt) or steno-occlusive vasculopathy by MRI of brain; urine albumin-to-creatinine ratio (UACR) \> 300 mg/g; extracellular volume fraction (ECV) \> 0.35 on cardiac MRI; or erythrocyte pit count \< 5%

  Through study completion, an average of 10 years

Secondary Outcomes (7)

• longitudinal change in fetal hemoglobin percentage (HbF%)

  Through study completion, an average of 10 years

• Longitudinal change in hemoglobin concentration (g/dL)

  Through study completion, an average of 10 years.

• Longitudinal change in reticulocyte count (10^9/L)

  Through study completion, an average of 10 years.

• Longitudinal change in absolute neutrophil count (10^9/L)

  Through study completion, an average of 10 years.

• Longitudinal change in mean cell volume (fL)

  Through study completion, an average of 10 years.

Study Arms (1)

Observational Treatment Group (Single Arm)

EXPERIMENTAL

All children with sickle cell anemia who are started on hydroxyurea for clinical indicators between 6 months and 5 years of age can do so on this observational study with PK-optimized hydroxyurea dosing.

Drug: PK-optimized oral hydroxyurea at MTD until 15 years of age.

Interventions

PK-optimized oral hydroxyurea at MTD until 15 years of age. DRUG

Because people are different, we will measure how each participant's body absorbs and eliminates the medicine, hydroxyurea, using blood tests. This information will be used to determine the best dose for each participant (rather than using the same weight-based dose for everyone).

Also known as: pharmacokinetic, maximum tolerated dose

Observational Treatment Group (Single Arm)

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of sickle cell anemia (HbSS) or sickle-β0-thalassemia (HbSβ0)
• Age 6 months at the time of enrollment
• Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy

You may not qualify if:

• Current treatment with regularly scheduled blood transfusions
• Sickle-hemoglobin C disease (HbSC), sickle-β+-thalassemia (HbSβ+)

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Greater Cincinnati Foundation: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Related Publications (13)

• Hay SB, Ferchen K, Chetal K, Grimes HL, Salomonis N. The Human Cell Atlas bone marrow single-cell interactive web portal. Exp Hematol. 2018 Dec;68:51-61. doi: 10.1016/j.exphem.2018.09.004. Epub 2018 Sep 21.

  PMID: 30243574 BACKGROUND

• Marahatta A, Megaraj V, McGann PT, Ware RE, Setchell KD. Stable-Isotope Dilution HPLC-Electrospray Ionization Tandem Mass Spectrometry Method for Quantifying Hydroxyurea in Dried Blood Samples. Clin Chem. 2016 Dec;62(12):1593-1601. doi: 10.1373/clinchem.2016.263715. Epub 2016 Sep 30.

  PMID: 27694393 BACKGROUND

• Vassiliou G. Telomere Length and Clonal Hematopoiesis. N Engl J Med. 2023 Jun 29;388(26):2481-2484. doi: 10.1056/NEJMe2303022. Epub 2023 May 4. No abstract available.

  PMID: 37140164 BACKGROUND

• Bowman RL, Busque L, Levine RL. Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies. Cell Stem Cell. 2018 Feb 1;22(2):157-170. doi: 10.1016/j.stem.2018.01.011.

  PMID: 29395053 BACKGROUND

• Sankaran VG, Xu J, Orkin SH. Advances in the understanding of haemoglobin switching. Br J Haematol. 2010 Apr;149(2):181-94. doi: 10.1111/j.1365-2141.2010.08105.x. Epub 2010 Mar 1.

  PMID: 20201948 BACKGROUND

• Ware RE, Davis BR, Schultz WH, Brown RC, Aygun B, Sarnaik S, Odame I, Fuh B, George A, Owen W, Luchtman-Jones L, Rogers ZR, Hilliard L, Gauger C, Piccone C, Lee MT, Kwiatkowski JL, Jackson S, Miller ST, Roberts C, Heeney MM, Kalfa TA, Nelson S, Imran H, Nottage K, Alvarez O, Rhodes M, Thompson AA, Rothman JA, Helton KJ, Roberts D, Coleman J, Bonner MJ, Kutlar A, Patel N, Wood J, Piller L, Wei P, Luden J, Mortier NA, Stuber SE, Luban NLC, Cohen AR, Pressel S, Adams RJ. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016 Feb 13;387(10019):661-670. doi: 10.1016/S0140-6736(15)01041-7. Epub 2015 Dec 6.

  PMID: 26670617 BACKGROUND

• Hankins JS, Helton KJ, McCarville MB, Li CS, Wang WC, Ware RE. Preservation of spleen and brain function in children with sickle cell anemia treated with hydroxyurea. Pediatr Blood Cancer. 2008 Feb;50(2):293-7. doi: 10.1002/pbc.21271.

  PMID: 17554794 BACKGROUND

• Letvin NL, Linch DC, Beardsley GP, McIntyre KW, Nathan DG. Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea. N Engl J Med. 1984 Apr 5;310(14):869-73. doi: 10.1056/NEJM198404053101401.

  PMID: 6199670 BACKGROUND

• Platt OS. Hydroxyurea for the treatment of sickle cell anemia. N Engl J Med. 2008 Mar 27;358(13):1362-9. doi: 10.1056/NEJMct0708272. No abstract available.

  PMID: 18367739 BACKGROUND

• Ware RE. Optimizing hydroxyurea therapy for sickle cell anemia. Hematology Am Soc Hematol Educ Program. 2015;2015:436-43. doi: 10.1182/asheducation-2015.1.436.

  PMID: 26637755 BACKGROUND

• Lanzkron S, Carroll CP, Haywood C Jr. Mortality rates and age at death from sickle cell disease: U.S., 1979-2005. Public Health Rep. 2013 Mar-Apr;128(2):110-6. doi: 10.1177/003335491312800206.

  PMID: 23450875 BACKGROUND

• Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44. doi: 10.1056/NEJM199406093302303.

  PMID: 7993409 BACKGROUND

• Vichinsky E, Hurst D, Earles A, Kleman K, Lubin B. Newborn screening for sickle cell disease: effect on mortality. Pediatrics. 1988 Jun;81(6):749-55.

  PMID: 3368274 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Aging; Pharmacogenomic Variants; Maximum Tolerated Dose

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Growth and Development; Physiological Phenomena; Polymorphism, Genetic; Genetic Variation; Genetic Phenomena; Toxicity Tests; Investigative Techniques; Toxicological Phenomena; Pharmacological and Toxicological Phenomena

Study Officials

• Charles T. Quinn, Professor of Pediatrics, M.D., M.S.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wendi L. Long, Sr. Regulatory Specialist, BS, CCRC

CONTACT

513-803-3064; wendi.long@cchmc.org

Teresa Latham, Research Director, DrPH

CONTACT

(513) 803-7922; teresa.latham@cchmc.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, open-label, single-arm therapeutic trial of pharmacokinetics (PK)-optimized oral hydroxyurea at maximum tolerated dose (MTD) for the treatment of sickle cell anemia (SCA) with long-term follow-up.

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: September 16, 2025
• Study Start: December 19, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 16, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)