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.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 12
- 主要终点
- AESI - Bacterial Infection
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 9 Months 至 23 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
-
干预措施: Xromi (Drug)
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.
结局指标
主要结局
AESI - Bacterial Infection
时间窗: 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
时间窗: 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
时间窗: 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.
AESI - Myelosuppression (Neutropenia)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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).
次要结局
- Other Adverse Events(Baseline to 24 months)
- Acute Chest Syndrome (ACS)(Pre-baseline, Baseline to 24 months)
- Splenomegaly(Pre-baseline, Baseline to 24 months)
- Priapism(Baseline to 24 months)
- Hepatobiliary disorder(Pre-baseline, Baseline to 24 months)
- Splenic Sequestration Crisis(Pre-baseline, Baseline to 24 months)
- Cerebrovascular accident(Pre-baseline, Baseline to 24 months)
- Hospitalisations for SCD(Pre-baseline, Baseline to 24 months)
- Other Clinical Events(Pre-baseline, Baseline to 24 months)
- Other Event - Death(Baseline to 24 months)
- Surgery(Pre-baseline, Baseline to 24 months)
- Blood Transfusion(Pre-baseline, Baseline to 24 months)
- Non-hospitalised Visit for SCD(Pre-baseline, Baseline to 24 months)
- Haemoglobin (Hb)(Pre-baseline, Baseline to 24 months)
- Foetal Haemoglobin (HbF)(Pre-baseline, Baseline to 24 months)
- Absolute Neutrophil Count (ANC)(Pre-baseline, Baseline to 24 months)
- Absolute Reticulocyte Count (ARC)(Pre-baseline, Baseline to 24 months)
- Platelet Count(Pre-baseline, Baseline to 24 months)
- White Blood Cell Count (WBC)(Pre-baseline, Baseline to 24 months)
- Mean Corpuscular Volume (MCV)(Pre-baseline, Baseline to 24 months)
- Mean Corpuscular Haemoglobin (MCH)(Pre-baseline, Baseline to 24 months)
- Ferritin(Pre-baseline, Baseline to 24 months)
- Transferrin Saturation(Pre-baseline, Baseline to 24 months)
- Alanine Transaminase (ALT)(Pre-baseline, Baseline to 24 months)
- Alkaline Phosphatase (ALP)(Pre-baseline, Baseline to 24 months)
- Aspartate Transaminase (AST)(Pre-baseline, Baseline to 24 months)
- Total Bilirubin(Pre-baseline, Baseline to 24 months)
- Lactate Dehydrogenase(Pre-baseline, Baseline to 24 months)
- Gamma-Glutamyl Transferase (GGT)(Pre-baseline, Baseline to 24 months)
- Serum Creatinine(Pre-baseline, Baseline to 24 months)
- Estimated Glomular Filtration Rate (eGFR)(Pre-baseline, Baseline to 24 months)
- Albumin-Creatinine Ratio (ACR)(Pre-baseline, Baseline to 24 months)
- Liver Size(Pre-baseline, Baseline to 24 months)
- Spleen Size(Pre-baseline, Baseline to 24 months)
- Maximum Time Averaged Mean Velocity (TAMV)(Pre-baseline, Baseline to 24 months)
- Painful Vaso-occlusive Crisis (VOC)(Pre-baseline, Baseline to 24 months)
- Abnormal or Conditional TCD(Pre-baseline, Baseline to 24 months)
- Haemoglobin Fractions(Pre-baseline, Baseline to 24 months)