Sickle Cell DiseasePRECISENCT06923111
PASS of Xromi Comparing Safety and Effectiveness in Children Under 2 Years With Sickle Cell Disease [PRECISE PASS]
An observational study of Sickle Cell Disease, run by Nova Laboratories Limited at 12 sites in 2 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 9 to 23 months
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Xromi
- Type of treatment
- Pill or oral medicine
- How many people
- 180 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 9 Jun 2025to Jun 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 to 23 months
- All sexes
- No healthy volunteers
- Child
Study population: The study population will consist of children with SCD who meet all the inclusion criteria and none of the exclusion criteria. Identification of participants will be conducted as follows: * Prospective exposure cohort: Potential participants will be identified as they attend the participating sites where eligibility criteria will be assessed prior to initiation with Xromi. * Retrospective comparator cohort: Potential participants will be selected from clinical chart review for hydroxycarbamide naive children that could be matched to prospective participants.
Who may be able to join
- 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.
- Aged from 9 months to under 2 years at the index date.
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- 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.
Who cannot join
- 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.
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- 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
- 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.
Trial locations and contacts
12 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 2 countries
United Kingdom10 sites, 10 recruiting
- Recruiting
Basildon University Hospital
Basildon
- Recruiting
Noah's Ark Children's Hospital for Wales
Cardiff
- Recruiting
Evelina London Children's Hospital
London
- Recruiting
Kings College Hospital
London
- Recruiting
North Middlesex University Hospital
London
- Recruiting
The Royal London Hospital
London
- Recruiting
University College London Hospital
London
- Recruiting
Whittington Hospital
London
- Recruiting
Royal Manchester Children's Hospital
Manchester
- Recruiting
John Radcliffe Hospital
Oxford
Germany2 sites, 2 recruiting
- Recruiting
Universitätsklinikum Hamburg-Eppendorf
Hamburg
- Recruiting
Universitätsklinikum Heidelberg
Heidelberg
About this study
Official 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.
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.
Read the detailed description
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.
- Conditions
- Sickle Cell Disease
- Being tested
- Xromi
- Keywords
- Hydroxyurea, liquid formulation, HbS Disease, Hemoglobin S Disease, Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorders, Sickling Disorder Due to Hemoglobin S, Xromi, Hydroxycarbamide, paediatric, children, hemaglobinopathy in children, hemoglobinopathy, paediatric formuation
- Medical subject headings
- Anemia, Sickle Cell, Hemoglobinopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XromiDrug
Also called hydroxycarbamide oral solution 100mg/ml, liquid hydroxyurea, LO1XX05
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
| Study group | Role | What they receive |
|---|---|---|
| Prospective Exposure Cohort | Children with SCD aged 9 months to under 2 years of age who are newly prescribed Xromi®, will be identified prospectively. These participants will be followed up for 24 months from their index date, regardless of whether they continue treatment with Xromi®, discontinue all hydroxycarbamide treatment, or switch to another formulation of hydroxycarbamide. The decision to prescribe Xromi® will be made solely by the physician independently of the study, as part of standard care.
- Receives: Drug: Xromi | |
| Retrospective Comparator Cohort | Children with SCD and naïve to any hydroxycarbamide formulation at the index date. These participants will be identified retrospectively using the data from the last 10 years up to the date Xromi® was first used in children from 9 months to under 2 years of age at each individual site. The 24-month follow-up will be retrospective from the date they are matched to the exposed participant, irrespective of whether they start on any formulation of hydroxycarbamide during the follow-up. |
What is being measured
The primary outcome is the main question the study is designed to answer.
AESI - Myelosuppression (Neutropenia)
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
Measured: Pre-baseline, Baseline to 24 months
AESI - Myelosuppression (Reticulocytopenia)
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,
Measured: Pre-baseline, Baseline to 24 months
AESI - Myelosuppression (Thrombocytopenia)
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.
Measured: Pre-baseline, Baseline to 24 months
AESI - Myelosuppression (Anaemia)
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.
Measured: Pre-baseline, Baseline to 24 months
AESI - Abnormal Weight Gain
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
Measured: Baseline to 24 months
AESI - Abnormal Weight Loss
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
Measured: Baseline to 24 months
AESI - Increase in Hepatic Enzyme (ALT)
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)
Measured: Baseline to 24 months
AESI - Increase in Hepatic Enzyme (AST)
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)
Measured: Baseline to 24 months
AESI - Alopecia
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).
Measured: Pre-baseline, Baseline to 24 months
AESI - Other Hair Loss
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).
Measured: Pre-baseline, Baseline to 24 months
AESI - Skin Hyperpigmentation
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).
Measured: Pre-baseline, Baseline to 24 months
AESI - Rash
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).
Measured: Pre-baseline, Baseline to 24 months
AESI - Skin Ulcers
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).
Measured: Pre-baseline, Baseline to 24 months
AESI - Growth Retardation
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).
Measured: Pre-baseline, Baseline to 24 months
AESI - Bacterial Infection
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.
Measured: Pre-baseline, Baseline to 24 months
AESI - Viral Infection
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.
Measured: Pre-baseline, Baseline to 24 months
AESI - Fungal Infection
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.
Measured: Pre-baseline, Baseline to 24 months
Secondary outcomes (38)
Other Adverse Events
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.
Measured: Baseline to 24 months
Painful Vaso-occlusive Crisis (VOC)
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.
Measured: Pre-baseline, Baseline to 24 months
Acute Chest Syndrome (ACS)
Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Measured: Pre-baseline, Baseline to 24 months
Splenomegaly
Occurrence of the clinical event Splenomegaly will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Measured: Pre-baseline, Baseline to 24 months
Priapism
Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Measured: Baseline to 24 months
Hepatobiliary disorder
Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Measured: Pre-baseline, Baseline to 24 months
Splenic Sequestration Crisis
Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Measured: Pre-baseline, Baseline to 24 months
Surgery
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.
Measured: Pre-baseline, Baseline to 24 months
Blood Transfusion
Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Measured: Pre-baseline, Baseline to 24 months
Cerebrovascular accident
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
Measured: Pre-baseline, Baseline to 24 months
Abnormal or Conditional TCD
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)
Measured: Pre-baseline, Baseline to 24 months
Hospitalisations for SCD
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.
Measured: Pre-baseline, Baseline to 24 months
Non-hospitalised Visit for SCD
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
Measured: Pre-baseline, Baseline to 24 months
Other Clinical Events
Occurrence of the clinical event will be collected during follow-up in both cohorts by the investigator to compare the Effectiveness of Xromi®.
Measured: Pre-baseline, Baseline to 24 months
Other Event - Death
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
Measured: Baseline to 24 months
Haemoglobin (Hb)
(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.
Measured: Pre-baseline, Baseline to 24 months
Foetal Haemoglobin (HbF)
(%) 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.
Measured: Pre-baseline, Baseline to 24 months
Haemoglobin Fractions
(%) 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
Measured: Pre-baseline, Baseline to 24 months
Absolute Neutrophil Count (ANC)
(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.
Measured: Pre-baseline, Baseline to 24 months
Absolute Reticulocyte Count (ARC)
(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.
Measured: Pre-baseline, Baseline to 24 months
Platelet Count
(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.
Measured: Pre-baseline, Baseline to 24 months
White Blood Cell Count (WBC)
(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.
Measured: Pre-baseline, Baseline to 24 months
Mean Corpuscular Volume (MCV)
(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.
Measured: Pre-baseline, Baseline to 24 months
Mean Corpuscular Haemoglobin (MCH)
(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.
Measured: Pre-baseline, Baseline to 24 months
Ferritin
(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.
Measured: Pre-baseline, Baseline to 24 months
Transferrin Saturation
(%) 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.
Measured: Pre-baseline, Baseline to 24 months
Alanine Transaminase (ALT)
(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.
Measured: Pre-baseline, Baseline to 24 months
Alkaline Phosphatase (ALP)
(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.
Measured: Pre-baseline, Baseline to 24 months
Aspartate Transaminase (AST)
(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.
Measured: Pre-baseline, Baseline to 24 months
Total Bilirubin
(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.
Measured: Pre-baseline, Baseline to 24 months
Lactate Dehydrogenase
(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.
Measured: Pre-baseline, Baseline to 24 months
Gamma-Glutamyl Transferase (GGT)
(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.
Measured: Pre-baseline, Baseline to 24 months
Serum Creatinine
(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.
Measured: Pre-baseline, Baseline to 24 months
Estimated Glomular Filtration Rate (eGFR)
(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.
Measured: Pre-baseline, Baseline to 24 months
Albumin-Creatinine Ratio (ACR)
(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.
Measured: Pre-baseline, Baseline to 24 months
Liver Size
(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.
Measured: Pre-baseline, Baseline to 24 months
Spleen Size
(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.
Measured: Pre-baseline, Baseline to 24 months
Maximum Time Averaged Mean Velocity (TAMV)
(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.
Measured: Pre-baseline, Baseline to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2025
- Study start9 Jun 2025
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nova Laboratories Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- OXON Epidemiology
- Responsible party
- Sponsor
- Investigators
- Hussain Dr Mulla, PhD, Study director, Nova Laboratories Ltd.Sara Dr Trompeter, MD, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06923111
- Sponsor's protocol ID
- NOVDD-001
- Other IDs
- EUPAS1000000076, CHIL 62837, 334976
- Acronym
- PRECISE
- Status last verified
- Mar 2026
- First submitted
- 3 Apr 2025
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study has been registered on a public database HMA-EMA RWD Catalogues and the study protocol has been shared publicly (EUPAS1000000076). Study publication of aggregated outcome results on Clinical trials.gov and in Multi-centre study publication in relevant medical journal. Investigators: All Investigators will be provided with their individual participant data at the end of the study as eCRFs. Regulatory Authorities: The study protocol was shared with the EMA and MHRA. The draft SAP was shared with the EMA during initial review of the study protocol prior to study initiation. CSR will be made available to the EMA and MHRA at the end of the study.
Publications
Rankine-Mullings A, Keenan R, Chakravorty S, Inusa B, Telfer P, Velangi M, Ware RE, Moss JJ, Lloyd AL, Edwards S, Mulla H. Efficacy, safety, and pharmacokinetics of a new, ready-to-use, liquid hydroxyurea in children with sickle cell anemia. Blood Adv. 2023 Aug 22;7(16):4319-4322. doi: 10.1182/bloodadvances.2023010099. No abstract available.
PubMed 37171600Thompson BW, Miller ST, Rogers ZR, Rees RC, Ware RE, Waclawiw MA, Iyer RV, Casella JF, Luchtman-Jones L, Rana S, Thornburg CD, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik S, Howard TH, Luck L, Wang WC. The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design. Pediatr Blood Cancer. 2010 Feb;54(2):250-5. doi: 10.1002/pbc.22269.
PubMed 19731330
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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.
- ClinicalTrials.gov ID
- NCT06923111
- Acronym / sponsor ID
- PRECISE / NOVDD-001
- Conditions
- Sickle Cell Disease
- Keywords
- Hydroxyurea, liquid formulation, HbS Disease, Hemoglobin S Disease, Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorders, Sickling Disorder Due to Hemoglobin S
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Nova Laboratories LimitedIndustry (pharma, biotech, devices)
- Collaborators
- OXON Epidemiology
- Study start
- 9 Jun 2025 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 11 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prospective Exposure Cohort | – | Drug: XromiChildren with SCD aged 9 months to under 2 years of age who are newly prescribed Xromi®, will be identified prospectively. These participants will be followed up for 24 months from their index date, regardless of whether they continue treatment with Xromi®, discontinue all hydroxycarbamide treatment, or switch to another formulation of hydroxycarbamide. The decision to prescribe Xromi® will be made solely by the physician independently of the study, as part of standard care. - |
| Retrospective Comparator Cohort | – | –Children with SCD and naïve to any hydroxycarbamide formulation at the index date. These participants will be identified retrospectively using the data from the last 10 years up to the date Xromi® was first used in children from 9 months to under 2 years of age at each individual site. The 24-month follow-up will be retrospective from the date they are matched to the exposed participant, irrespective of whether they start on any formulation of hydroxycarbamide during the follow-up. |
Who may qualify
- Ages
- 9 to 23 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The study population will consist of children with SCD who meet all the inclusion criteria and none of the exclusion criteria. Identification of participants will be conducted as follows: * Prospective exposure cohort: Potential participants will be identified as they attend the participating sites where eligibility criteria will be assessed prior to initiation with Xromi. * Retrospective comparator cohort: Potential participants will be selected from clinical chart review for hydroxycarbamide naive children that could be matched to prospective participants.
Key inclusion criteria (10 listed)
Key exclusion criteria (15 listed)
- Participants in the prospective exposure cohort who are prescribed Xromi® but do not initiate treatment will be excluded from the dataset.
- Retrospective Comparator cohort
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XromiAlso: hydroxycarbamide oral solution 100mg/ml, liquid hydroxyurea, LO1XX05Xromi 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 | Drug | Prospective Exposure Cohort |
Primary outcome
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
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,
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.
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.
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
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
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)
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)
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).
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).
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).
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).
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).
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).
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.
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.
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.
38 secondary outcomes
Other Adverse Events
Time frame: Baseline to 24 months
Painful Vaso-occlusive Crisis (VOC)
Time frame: Pre-baseline, Baseline to 24 months
Acute Chest Syndrome (ACS)
Time frame: Pre-baseline, Baseline to 24 months
Splenomegaly
Time frame: Pre-baseline, Baseline to 24 months
Priapism
Time frame: Baseline to 24 months
Hepatobiliary disorder
Time frame: Pre-baseline, Baseline to 24 months
Splenic Sequestration Crisis
Time frame: Pre-baseline, Baseline to 24 months
Surgery
Time frame: Pre-baseline, Baseline to 24 months
Blood Transfusion
Time frame: Pre-baseline, Baseline to 24 months
Cerebrovascular accident
Time frame: Pre-baseline, Baseline to 24 months
Abnormal or Conditional TCD
Time frame: Pre-baseline, Baseline to 24 months
Hospitalisations for SCD
Time frame: Pre-baseline, Baseline to 24 months
Non-hospitalised Visit for SCD
Time frame: Pre-baseline, Baseline to 24 months
Other Clinical Events
Time frame: Pre-baseline, Baseline to 24 months
Other Event - Death
Time frame: Baseline to 24 months
Haemoglobin (Hb)
Time frame: Pre-baseline, Baseline to 24 months
Foetal Haemoglobin (HbF)
Time frame: Pre-baseline, Baseline to 24 months
Haemoglobin Fractions
Time frame: Pre-baseline, Baseline to 24 months
Absolute Neutrophil Count (ANC)
Time frame: Pre-baseline, Baseline to 24 months
Absolute Reticulocyte Count (ARC)
Time frame: Pre-baseline, Baseline to 24 months
Platelet Count
Time frame: Pre-baseline, Baseline to 24 months
White Blood Cell Count (WBC)
Time frame: Pre-baseline, Baseline to 24 months
Mean Corpuscular Volume (MCV)
Time frame: Pre-baseline, Baseline to 24 months
Mean Corpuscular Haemoglobin (MCH)
Time frame: Pre-baseline, Baseline to 24 months
Ferritin
Time frame: Pre-baseline, Baseline to 24 months
Transferrin Saturation
Time frame: Pre-baseline, Baseline to 24 months
Alanine Transaminase (ALT)
Time frame: Pre-baseline, Baseline to 24 months
Alkaline Phosphatase (ALP)
Time frame: Pre-baseline, Baseline to 24 months
Aspartate Transaminase (AST)
Time frame: Pre-baseline, Baseline to 24 months
Total Bilirubin
Time frame: Pre-baseline, Baseline to 24 months
Lactate Dehydrogenase
Time frame: Pre-baseline, Baseline to 24 months
Gamma-Glutamyl Transferase (GGT)
Time frame: Pre-baseline, Baseline to 24 months
Serum Creatinine
Time frame: Pre-baseline, Baseline to 24 months
Estimated Glomular Filtration Rate (eGFR)
Time frame: Pre-baseline, Baseline to 24 months
Albumin-Creatinine Ratio (ACR)
Time frame: Pre-baseline, Baseline to 24 months
Liver Size
Time frame: Pre-baseline, Baseline to 24 months
Spleen Size
Time frame: Pre-baseline, Baseline to 24 months
Maximum Time Averaged Mean Velocity (TAMV)
Time frame: Pre-baseline, Baseline to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
- Background: PubMed 37171600Rankine-Mullings A, Keenan R, Chakravorty S, Inusa B, Telfer P, Velangi M, Ware RE, Moss JJ, Lloyd AL, Edwards S, Mulla H. Efficacy, safety, and pharmacokinetics of a new, ready-to-use, liquid hydroxyurea in children with sickle cell anemia. Blood Adv. 2023 Aug 22;7(16):4319-4322. doi: 10.1182/bloodadvances.2023010099. No abstract available.
- Background: PubMed 19731330Thompson BW, Miller ST, Rogers ZR, Rees RC, Ware RE, Waclawiw MA, Iyer RV, Casella JF, Luchtman-Jones L, Rana S, Thornburg CD, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik S, Howard TH, Luck L, Wang WC. The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design. Pediatr Blood Cancer. 2010 Feb;54(2):250-5. doi: 10.1002/pbc.22269.
- Individual participant dataSharing planned: Yes. The study has been registered on a public database HMA-EMA RWD Catalogues and the study protocol has been shared publicly (EUPAS1000000076). Study publication of aggregated outcome results on Clinical trials.gov and in Multi-centre study publication in relevant medical journal. Investigators: All Investigators will be provided with their individual participant data at the end of the study as eCRFs. Regulatory Authorities: The study protocol was shared with the EMA and MHRA. The draft SAP was shared with the EMA during initial review of the study protocol prior to study initiation. CSR will be made available to the EMA and MHRA at the end of the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hussain Dr Mulla, PhD study director
Nova Laboratories Ltd.
Sara Dr Trompeter, MD principal investigator
University College London Hospitals
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by Nova Laboratories Limited at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hussain Mulla, PhD (+44 (0)116 223 0100, hussain.mulla@novalabs.co.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AESI - Myelosuppression (Neutropenia) (time frame: Pre-baseline, Baseline to 24 months). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06923111, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.