Skip to main content
OpenTrials
Recruiting

NCT Number: NCT06923111

PASS of Xromi Comparing Safety and Effectiveness in Children Under 2 Years With Sickle Cell Disease [PRECISE PASS]

This post-authorisation safety and efficacy study (PRECISE PASS) evaluates the use of Xromi® (hydroxycarbamide 100 mg/mL oral solution) in children aged 9 months to under 2 years with sickle cell disease (SCD).

The objective is to assess the safety profile and clinical effectiveness of Xromi® under routine clinical conditions. The study includes a prospective cohort of Xromi®-treated patients and a matched retrospective comparator cohort of untreated patients. Participants will be followed for 24 months from treatment initiation or matched index date.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

9 month–23 month

Sex eligibility

All sexes

Study type

Observational

Primary location

Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Loading trial locations.

About this study

The PRECISE study is a combined Post-Authorisation Safety Study (PASS) (Category 3) and a Post-Authorisation Efficacy Study that aims to provide data on the safety and effectiveness of hydroxycarbamide 100mg/ml oral solution (Xromi ®) administered prospectively to children under 2 years of age, over a follow-up period of 24 months compared to matched retrospective comparators who were treatment naïve.

This is a non-interventional, matched cohort study involving children with SCD aged 9 to under 24 months. The study comprises two groups:

  • A prospective Xromi®-exposed cohort, enrolled at the time of treatment initiation and followed for 24 months.
  • A retrospective comparator cohort, matched 2:1 by site, age, and β-globin genotype, identified from clinical records of children not treated with hydroxycarbamide at the index date.

The primary objective is to compare the incidence of adverse events of special interest (AESIs) between the two cohorts. Secondary analyses will assess the comparative effectiveness of Xromi® on clinical events, laboratory parameters, and physiological assessments. Exploratory analyses will examine treatment-related safety and effectiveness by dose, subgroups, and exposure to hydroxycarbamide during follow-up.

Data will be sourced from routine clinical practice through chart reviews and follow-up visits. No study-specific interventions will be introduced. The study is planned across specialist sites in the UK and Germany, with potential expansion to other European countries if recruitment targets require.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Prospective Exposure Cohort

  • Inclusion criteria:
  • Aged from 9 months to under 2 years at the index date.
  • Diagnosis of SCD.
  • Known β-globin genotype at the index date.
  • Prescribed Xromi® for the prevention of complications of SCD.
  • Parent(s) (or a legal representative(s)) provides written informed consent to participate in the study, unless there is a waiver, non-opposition, or blanket written informed consent by the parent for research studies.
  • Exclusion criteria:
  • Previous use of hydroxycarbamide of any formulation before the index date.
  • Receiving regular blood transfusions (occurring every 8 weeks or more frequently) at the index date.
  • Known hypersensitivity to any of the excipients of Xromi® at the index date.
  • Contraindications to the drug at the index date: severe hepatic impairment (Child-Pugh classification C); severe renal impairment (creatinine clearance: CrCl <30 ml/min); presence of at least one of the following: Absolute neutrophil count (ANC) < 1.0 x 10^9/L, absolute reticulocyte count (ARC) <80 x 10^9/L, platelets <80 x 10^9/L.
  • Participating in another clinical study of an investigational medicinal product (IMP) at the index date.
  • Anti-retroviral medicinal products for human immunodeficiency virus (HIV) at the index date.
  • Active malignancy at the index date.

Participants in the prospective exposure cohort who are prescribed Xromi® but do not initiate treatment will be excluded from the dataset.

Retrospective Comparator cohort

  • Inclusion criteria:
  • Aged from 9 months to under 2 years at the index date.
  • Diagnosis of SCD.
  • Known β-globin genotype.
  • Matched to an exposed participant.
  • Parent(s) (or a legal representative(s)) provides written informed consent to participate in the study, unless there is a waiver, non-opposition, or blanket written informed consent by the parent for research studies.
  • Exclusion criteria:
  • Use of hydroxycarbamide of any formulation before or at the index date.
  • Receiving regular blood transfusions (occurring every 8 weeks or more frequently) at the index date.
  • Presence at the index date of any of the following: severe hepatic impairment (Child-Pugh classification C); severe renal impairment (CrCl <30 ml/min); presence of at least one of the following: ANC < 1.0 x 10^9/L, ARC < 80 x 10^9/L, platelets < 80 x 10^9/L).
  • Participating in another clinical study of an IMP at the index date.
  • Anti-retroviral medicinal products for HIV at the index date.
  • Active malignancy at the index date.

Treatment and study plan

Xromi

Drug

Xromi is indicated for the prevention of vaso-occlusive complications of Sickle Cell Disease in patients over 9 months of age as part of standard clinical practice

Other names: hydroxycarbamide oral solution 100mg/ml, liquid hydroxyurea, LO1XX05

Primary outcomes

  1. AESI - Myelosuppression (Neutropenia)

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Myelosuppression protocol definition of neutropenia is ANC <1.0 x 10^9/L

  2. AESI - Myelosuppression (Reticulocytopenia)

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Myelosuppression protocol definition of reticulocytopenia is ARC <80 x 10^9/L, unless Hb >90 g/L,

  3. AESI - Myelosuppression (Thrombocytopenia)

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Myelosuppression protocol definition of thrombocytopenia defined as platelets <80 x 10^9/L.

  4. AESI - Myelosuppression (Anaemia)

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Myelosuppression protocol definition of anaemia defined as Hb <45 g/L.

  5. AESI - Abnormal Weight Gain

    Time frame: Baseline to 24 months

    Weight (kg) Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and standard care guidelines

  6. AESI - Abnormal Weight Loss

    Time frame: Baseline to 24 months

    Weight (kg) Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and standard care guidelines

  7. AESI - Increase in Hepatic Enzyme (ALT)

    Time frame: Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and normal laboratory ranges. Defined as an increase in hepatic enzyme Alanine transaminase (ALT) increased (U/L)

  8. AESI - Increase in Hepatic Enzyme (AST)

    Time frame: Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and normal laboratory ranges. Defined as an increase in hepatic enzyme Aspartate transaminase (AST) increased (U/L)

  9. AESI - Alopecia

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of alopecia (a skin and subcutaneous tissue disorder).

  10. AESI - Other Hair Loss

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of other hair loss (a skin and subcutaneous tissue disorder).

  11. AESI - Skin Hyperpigmentation

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of skin hyperpigmentation, including oral and nail hyperpigmentation.(a skin and subcutaneous tissue disorder).

  12. AESI - Rash

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of a rash (a skin and subcutaneous tissue disorder).

  13. AESI - Skin Ulcers

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in study protocol as presence of skin ulcer, including leg ulcer (a skin and subcutaneous tissue disorder).

  14. AESI - Growth Retardation

    Time frame: Pre-baseline, Baseline to 24 months

    height/length (cm) Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort and standard care guidelines (as a drop of 2 or more centiles on growth charts over time).

  15. AESI - Bacterial Infection

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in the protocol as a proven or treated bacterial infection.

  16. AESI - Viral Infection

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in the protocol as a proven or treated viral infection.

  17. AESI - Fungal Infection

    Time frame: Pre-baseline, Baseline to 24 months

    Incidence of adverse events of special interest (AESIs) in children who have SCD and are treated with Xromi®, in comparison to a retrospective comparator cohort. Defined in the protocol as a proven or treated fungal infection.

Secondary outcomes

  1. Other Adverse Events

    Time frame: Baseline to 24 months

    Occurrence of other adverse events (AE), adverse reactions (AR) and serious adverse events (SAE) or serious adverse reactions (SAR) will be collected during follow-up.

  2. Painful Vaso-occlusive Crisis (VOC)

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

    • VOC events will include dactylitis.

  3. Acute Chest Syndrome (ACS)

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

  4. Splenomegaly

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event Splenomegaly will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

  5. Priapism

    Time frame: Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

  6. Hepatobiliary disorder

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

  7. Splenic Sequestration Crisis

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

  8. Surgery

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

    Defined in the protocol as any surgery that is planned, emergency, or due to pre-existing conditions e.g. SCD.

  9. Blood Transfusion

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

  10. Cerebrovascular accident

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

    The protocol definition includes silent stroke

  11. Abnormal or Conditional TCD

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

    • Transcranial Doppler Scan (TCD)

  12. Hospitalisations for SCD

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

    The reason for hospitalisation and duration will be collected.

  13. Non-hospitalised Visit for SCD

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

    Protocol definition includes Emergency department (ED) visits/treatment centres/paediatric ward/day unit attendances for SCD

  14. Other Clinical Events

    Time frame: Pre-baseline, Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.

  15. Other Event - Death

    Time frame: Baseline to 24 months

    Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator. Protocol definition includes any death occurring in the study both related and un-related to Xromi treatment

  16. Haemoglobin (Hb)

    Time frame: Pre-baseline, Baseline to 24 months

    (g/L) or (g/dl) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  17. Foetal Haemoglobin (HbF)

    Time frame: Pre-baseline, Baseline to 24 months

    (%) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  18. Haemoglobin Fractions

    Time frame: Pre-baseline, Baseline to 24 months

    (%) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

    • Haemoglobinopathy screen results including: HbS, HbA, HbA2, HbC

  19. Absolute Neutrophil Count (ANC)

    Time frame: Pre-baseline, Baseline to 24 months

    (10^9/L or /nL) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  20. Absolute Reticulocyte Count (ARC)

    Time frame: Pre-baseline, Baseline to 24 months

    (10^9/L or /nL) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  21. Platelet Count

    Time frame: Pre-baseline, Baseline to 24 months

    (10^9/L or /nL) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  22. White Blood Cell Count (WBC)

    Time frame: Pre-baseline, Baseline to 24 months

    (10^9/L or /nL) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  23. Mean Corpuscular Volume (MCV)

    Time frame: Pre-baseline, Baseline to 24 months

    (fl) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  24. Mean Corpuscular Haemoglobin (MCH)

    Time frame: Pre-baseline, Baseline to 24 months

    (pg) Haematological Parameter. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  25. Ferritin

    Time frame: Pre-baseline, Baseline to 24 months

    (µg/L) Iron Profile. Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  26. Transferrin Saturation

    Time frame: Pre-baseline, Baseline to 24 months

    (%) Iron Profile. Iron binding saturation or transferrin saturation.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  27. Alanine Transaminase (ALT)

    Time frame: Pre-baseline, Baseline to 24 months

    (U/L) Liver Function tests.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  28. Alkaline Phosphatase (ALP)

    Time frame: Pre-baseline, Baseline to 24 months

    (U/L) Liver Function tests.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  29. Aspartate Transaminase (AST)

    Time frame: Pre-baseline, Baseline to 24 months

    (U/L) Liver Function tests.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  30. Total Bilirubin

    Time frame: Pre-baseline, Baseline to 24 months

    (µmol/L or mg/dl) Liver Function tests.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  31. Lactate Dehydrogenase

    Time frame: Pre-baseline, Baseline to 24 months

    (U/L) Liver Function tests.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  32. Gamma-Glutamyl Transferase (GGT)

    Time frame: Pre-baseline, Baseline to 24 months

    (U/L) Liver Function tests.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  33. Serum Creatinine

    Time frame: Pre-baseline, Baseline to 24 months

    (µmol/L or mg/dl) Renal function test.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  34. Estimated Glomular Filtration Rate (eGFR)

    Time frame: Pre-baseline, Baseline to 24 months

    (ml/min/1.73m^2) Renal function test. Calculated value, Interpreted in line with UK CKD guidelines from creatinine values.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  35. Albumin-Creatinine Ratio (ACR)

    Time frame: Pre-baseline, Baseline to 24 months

    (Calculated value). Renal function test.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  36. Liver Size

    Time frame: Pre-baseline, Baseline to 24 months

    (cm) from costal margin. Physiological Assessment.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  37. Spleen Size

    Time frame: Pre-baseline, Baseline to 24 months

    (cm) from costal margin. Physiological Assessment.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

  38. Maximum Time Averaged Mean Velocity (TAMV)

    Time frame: Pre-baseline, Baseline to 24 months

    (cm/s) Cardiovascular function, assessed using transcranial doppler scan velocities.

    Results and dates of laboratory tests and physiological assessments will be collected, whenever available. At baseline, the most recent results, prior to Xromi® initiation in the prospective exposure cohort, will be collected. Results from laboratory tests and physiological assessments conducted during follow-up will also be collected.

Study contacts

Contact information is provided by the study sponsor or research team.

Hussain Mulla, PhD

CONTACT

[email protected]

+44 (0)116 223 0100

Sarah Edwards, PhD

CONTACT

[email protected]

+44 (0)116 223 0100

Sponsors and collaborators

Lead sponsor

Nova Laboratories Limited

Industry

Collaborators

  • OXON Epidemiology

Registry information

Official study title

A Comparative Observational Study to Evaluate the Safety and Effectiveness of Xromi (Hydroxycarbamide Oral Solution 100mg/ml) for the Prevention of Vaso-occlusive Complications of Sickle Cell Disease in Children Under 2 Years of Age.

Acronym: PRECISE

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Apr 11, 2025
Registry last updated
Mar 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.