Haematological Disorders
Conditions
Interventions
Ticagrelor
Placebo
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply: 1 Provision of signed and dated informed consent prior to any study specific procedures not part of standard medical care (local regulations and international guidelines are to be followed in determining the assent/consent requirements for children). The Informed consent form (ICF) process is described in Appendix A 3. 2 Children aged 6 months to <18 years of age and body weight =6 kg diagnosed with HbSS or HbS/ß0 as confirmed by high-performance liquid chromatography (HPLC) or haemoglobin electrophoresis. Note: Diagnosis of SCD (if not confirmed prior to screening and records not available on the medical file) should be confirmed for HbSS or HbS/ß0 by HPLC or haemoglobin electrophoresis, performed at the site’s local laboratory, in order to confirm the type of mutation. Children being judged to be severely underweight (<3rd percentile according the World Health Organisation [WHO] growth charts) cannot be included. 3 Have experienced at least 2 VOCs (painful crisis and/or ACS) as judged by the Investigator in the past 12 months prior to Visit R1 (patients aged 6 to <24 months) or Visit 1 (patients aged 2 to <18 years). These VOCs need to be documented in the patient’s medical records or in other documents that can be reconciled. 4 If aged 2 to =16 years, must have had a TCD within the past year prior to Visit 2 (see Yawn et al 2014). If this is not the case, a TCD examination must be done before randomisation. 5 If aged =10 years, must have had an ophthalmological examination within the past year prior to Visit 1 (see Yawn et al 2014). If this is not the case, the patient must be examined by an ophthalmologist before proceeding in the study. If local guidelines dictate ophthalmological examination at younger ages, those local guidelines should be followed. 6 If treated with hydroxyurea or L-glutamine, the weight-adjusted d
Exclusion criteria
Exclusion criteria: 1 As judged by the Investigator, any evidence of unsuitability which in the Investigator’s opinion makes it undesirable for the patient to participate in the study. 2 History of transient ischaemic attack (TIA) or cerebrovascular accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy. 3 Findings on TCD: Current or previous values for time averaged mean of the maximum velocity (TAMMV) that are Conditional or Abnormal. Patients with Conditional TAMMV values or higher (=153 cm/sec using TCD imaging technique [TCDi] which is corresponding to =170 cm/sec by the non-imaging technique). Both the middle cerebral artery and the internal carotid artery should be considered. Any other criteria that would locally be considered as TCD indications for chronic transfusion would also exclude the patient. 4 Pathological finding on any other imaging assay indicating increased risk for intracerebral bleeding or thromboembolism. 5 International normalised ratio (INR) >1.4 or active pathological bleeding or increased risk of bleeding complications according to Investigator. 6 Haemoglobin 3 days per week that cannot be discontinued (see Appendix K). 10 Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued. 11 Moderate or severe hepatic impairment defined as laboratory values of alanine aminotransferase (ALT) >2×upper limit of normal (ULN), total bilirubin >2×ULN (unless judged by the Investigator to be cau
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of VOCs | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of VOCs in patients aged 2 to <18 years;Number of painful crises;Number of ACSs;Duration of painful crises;Number of VOCs requiring hospitalisation or emergency department visits;Number of days hospitalised for VOC;Number of acute SCD complications;Number of days hospitalised for acute SCD complications;Number of sickle cell-related RBC transfusions ;HRQL total score and by dimension using Paediatric Quality of Life Inventory (PedsQL) SCD Module; and Fatigue total score and by dimension using the PedsQL Multidimensional Fatigue Scale (age appropriate versions: 2 to 4 years; 5 to 7 years; 8 to 12 years; 13 to 18 years); HRQL total score and by dimension using the PedsQL Infant Scale (age appropriate versions: 1 to 12 months; 13 to 24 months);Proportion of days of absence from school or work (only if going to school or work at randomisation);Intensity of worst pain daily during VOC • For patients aged =4 years, observer reported using the Face, Legs, Activity, Cry, Consolability (FLACC) scale • For patients aged 5 to <18 years, self-reported using the Faces Pain Scale - Revised (FPS-R) ;Type of analgesics (opioid and non-opioid) use;• For patients aged =4 years taking the tablet dispersed or whole, an observer assessment of palatability and swallowability will be undertaken • For patients aged =5 years taking the tablet dispersed or whole, palatability will be assessed and categorised using the Facial Hedonic Scale ;Adverse Events (AE)/Serious Adverse Events (SAEs) including bleeding Vital signs and laboratory safety variables ;Duration of ACS;Population PK parameters such as oral clearance (CL/F) and ticagrelor exposure (AUC) | — |
Countries
Ghana, Kenya, Nigeria, Tanzania, Uganda
Contacts
Public ContactIssa ;Iheanyi Sabi;Okpala
Principal Investigator and National Coordinator;Principal Investigator and National coordinator
Outcome results
None listed