A Randomised, Double Blind, Parallel Group, Multicentre, Phase III Study to Evaluate the Effect of Ticagrelor versus Placebo in Reducing the Number of Vaso-Occlusive Crises in Paediatric Patients Aged 6 Months to <18 Years with Sickle Cell Disease (HESTIA5)
- Conditions
- Haematological Disorders
- Registration Number
- PACTR202003558059352
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 8
Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply:
1Provision 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.
2Children 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.
3Have 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.
4If 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.
5If 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.
6If treated with hydroxyurea or L-glutamine, the weight-adjusted d
1As 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.
2History of transient ischaemic attack (TIA) or cerebrovascular accident (ischaemic or haemorrhagic), severe head trauma, intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy.
3Findings 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.
4Pathological finding on any other imaging assay indicating increased risk for intracerebral bleeding or thromboembolism.
5International normalised ratio (INR) >1.4 or active pathological bleeding or increased risk of bleeding complications according to Investigator.
6Haemoglobin <6 g/dL from test performed at Visit R1 and Visit 1 (patients aged 6 to <24 months) or at Enrolment (Visit 1) (patients aged 2 to <18 years).
7Platelets <100 × 109/L from test performed at Visit R1 and Visit 1 (patients aged 6 to <24 months) or at Enrolment (Visit 1) (patients aged 2 to <18 years).
8Undergoing treatment with chronic red blood cell transfusion therapy.
9Chronic use of NSAIDs defined as continuous intake >3 days per week that cannot be discontinued (see Appendix K).
10Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
11Moderate 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method umber of VOCs
- Secondary Outcome Measures
Name Time Method