Sickle Cell DiseasePhase 3HESTIA5NCT04293172
Study to Evaluate the Effect of Ticagrelor Versus Placebo in Reducing Vaso-Occlusive Crises Rate in Pediatric Patients With Sickle Cell Disease.
A Phase 3 study testing Brilinta in people with Sickle Cell Disease, run by AstraZeneca.
Trial summary
The purpose of this study is to compare the effect of ticagrelor vs placebo for the reduction of Vaso-Occlusive crises in paediatric patients with Sickle Cell Disease Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Brilinta
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Jun 2020to 10 Oct 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
- Children aged 6 months to <18 years of age and body weight ≥6 kg diagnosed with HbSS or HbS/β0 as confirmed by high-performance liquid chromatography (HPLC) or haemoglobin electrophoresis.
- Have experienced at least 2 VASO-OCCLUSIVE CRISES (painful crisis and/or ACUTE CHEST SYNDROME) 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 VASO-OCCLUSIVE CRISES need to be documented in the patient's medical records or in other documents that can be reconciled.
- If aged 2 to ≤16 years, must have had a TCD within the past year prior to Visit 2. If this is not the case, a TCD examination must be done before randomisation.
- If aged ≥10 years, must have had an ophthalmological examination within the past year prior to Visit 1. 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.
- If treated with hydroxyurea or L-glutamine, the weight-adjusted dose must be stable for 3 months before screening.
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- Suitable venous access for the study-related blood sampling.
- Prior to dosing on day of randomisation (Visit 2), a negative urine (dipstick) pregnancy test performed at Enrolment (Visit 1) and at Visit 2 must be available for female patients of childbearing potential.
- Females of childbearing potential (after menarche) must not become pregnant during the study. Sexually active females must use a highly effective method of contraception which results in a low failure rate (ie, less than 1% per year). If use of effective contraception cannot be secured in sexually active females, the patient cannot be included in this study.
Who cannot join
- 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.
- 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.
- 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.
- Pathological finding on any other imaging assay indicating increased risk for intracerebral bleeding or thromboembolism.
- International normalised ratio (INR) >1.4 or active pathological bleeding or increased risk of bleeding complications according to Investigator.
- Haemoglobin <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).
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- Platelets <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).
- Undergoing treatment with chronic red blood cell transfusion therapy.
- Chronic use of NSAIDs defined as continuous intake >3 days per week that cannot be discontinued.
- Receiving chronic treatment with anticoagulants or antiplatelet drugs that cannot be discontinued.
- 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 caused by haemolysis), albumin <35 g/L (3.5 g/dL) and INR >1.4, or symptoms of liver disease (eg, ascites) 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).
- Renal failure requiring dialysis.
- Patient considered to be at risk of bradycardic events (eg, known sick sinus syndrome or second- or third-degree atrioventricular block) unless already treated with a permanent pacemaker.
- Concomitant oral or intravenous therapy with strong cytochrome P450 3A (CYP3A) inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers, which cannot be stopped at least 5 half-lives before randomisation.
- Active untreated malaria. Patients with suspected malaria at Visit R1 (patients aged 6 to <24 months) or at Enrolment (Visit 1) (patients aged 2 to <18 years) will be tested.
- Known hypersensitivity or contraindication to ticagrelor.
- Patients who are currently pregnant or breastfeeding or planning to become pregnant during the study or have given birth less than 3 months prior to Enrolment (Visit 1).
- Concern for the inability of the patient or caregiver (defined as legally authorised representative) to comply with study procedures and/or follow-up.
- Previous randomisation in the present study or participation in any previous HESTIA study.
- Participation in another clinical study with an IP or device during the last 30 days preceding screening.
- Involvement of member of patient's family, or patient self, in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
About this study
Official title: 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)
The purpose of this study is to compare the effect of ticagrelor vs placebo for the reduction of Vaso-Occlusive crises in paediatric patients with Sickle Cell Disease
Read the detailed description
- HESTIA5 will evaluate the efficacy, safety and tolerability of ticagrelor versus placebo in children with SICKLE CELL DISEASE during treatment for at least 12 months and up to a maximum of 24 months.
- The target population are children (males and females) aged 6 months to <18 years and body weight ≥6 kg diagnosed with homozygous sickle cell or sickle beta-zero-thalassaemia confirmed by high-performance liquid chromatography or hemoglobin electrophoresis. The aim is to randomise 20 patients in the age group 6 to <24 months. At least 50 patients should be randomised in each of the age groups: ≥2 to <12 years and ≥12 to <18 years.
- Prior to randomisation in this study, patients aged 6 to <24 months will undergo a 14-day Run in period in which they will receive open-label ticagrelor twice a day for 14 days according to weight. Run-in period includes 4 visits, called R1, R2, R3 and R4. The run-In period is to ensure that the treatment is well-tolerated, and that the exposure is in line with model-based predictions following repeated twice a day dosing with ticagrelor in this age group. At the end of the Run-in period (Visit R4), the patient will take his/her final dose of open-label IP and await the independent Data Monitoring Committee chairman's evaluation of tolerability, safety and exposure before being eligible to enter the Screening period for randomisation. Patients who complete the Run-in period according to the protocol must also meet all the inclusion/exclusion criteria detailed in Protocol, to proceed to randomisation.
- To be eligible for the study, patients must have experienced at least 2 VASO-OCCLUSIVE CRISES (defined as painful crisis and/or ACUTE CHEST SYNDROME) events in the past 12 months prior to Visit 1, (patients aged 2 to <18 years) and prior to visit R1 (patients aged 6 to <24 months) indicating that the severity of the patient's disease justifies preventive chronic long-term treatment. Even if painful VASO-OCCLUSIVE CRISES are uncommon in infants and become more frequent in older children, data show that symptoms like dactylitis precede more severe events and confirm that children who have early dactylitis are more likely to have severe events later in life.
- Study participants should receive standard of care for SICKLE CELL DISEASE, adjusted to the individual patient at the discretion of the investigator, including routine health care screening examinations and immunizations to local guidelines and health care programmes. Study drug will be given on the background of standard treatments for SICKLE CELL DISEASE. Study participants are not withheld from any other treatments that may be used in SICKLE CELL DISEASE (eg., hydroxyurea) during the trial, which is important considering the use of a placebo control group. However, restrictions apply to some medications and interventions that may be necessary for the patient's health and well-being during the study.
- Patients are to be followed until a common study end date (CSED) is reached defined as 12 months after the last patient is randomized. Treatment duration is at least 12 months for study participants, and patients will continue on treatment until 12 months after last randomized patient or up to a maximum of 24 months. The expected average follow-up is 18 months, assuming a uniformly distributed enrolment period of 12 months. Considering inclusion of patients with at least 2 VASO-OCCLUSIVE CRISES in the past year, this treatment duration is considered long enough to evaluate effects on VASO-OCCLUSIVE CRISES events as well as to capture safety and tolerability data supporting a potential future long term use of ticagrelor.
- Due to ticagrelor mechanism of action and the potential to reduce symptoms caused by ischemia during a vaso-occlusion, a composite endpoint with painful crises and/or ACUTE CHEST SYNDROME has been selected for the primary endpoint. Painful crisis is the most common reason for emergency department visits for patients with SICKLE CELL DISEASE with a significant impact on young patients' lives, affecting them physically and emotionally. Secondary endpoints are included to broaden the understanding of effects in patients with SICKLE CELL DISEASE and to also assess potential benefits on symptomatic disease burden and health-related quality of life (HRQL).
- Patients will be treated with 5, 10, 15, 30 and 45 mg twice a day or matching placebo, depending on body weight.
- Conditions
- Sickle Cell Disease
- Being tested
- Brilinta, Placebo
- Keywords
- Ticagrelor, Vaso-Occlusive Crises, Paediatric Patients, 6 Months to <18 Years, Sickle Cell Disease, Sickle Cell Anemia, Platelet aggregation, Brillinta, Acute Chest Syndrome, painful crisis
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises, Acute Chest Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrilintaDrug
Patients in the open-label Run-in period (patients aged 6 to <24 months only) will receive ticagrelor 5 mg twice a day (body weight 6 to ≤9 kg), 10 mg twice a day (body weight >9 to ≤12 kg) or 15 mg twice a day (body weight >12 to ≤24 kg) for 14 days.
The double-blind IP will be based on 5 weight bands:
- 6 to ≤9 kg: ticagrelor 5 mg or matching placebo, twice a day
- >9 to ≤12 kg: ticagrelor 10 mg or matching placebo, twice a day
- >12 to ≤24 kg: ticagrelor 15 mg or matching placebo, twice a day
- >24 to ≤48 kg: ticagrelor 30 mg or matching placebo, twice a day
- >48 kg: ticagrelor 45 mg or matching placebo, twice a day
PlaceboDrug
Patients in the open-label Run-in period (patients aged 6 to <24 months only) will receive ticagrelor 5 mg twice a day (body weight 6 to ≤9 kg), 10 mg twice a day (body weight >9 to ≤12 kg) or 15 mg twice a day (body weight >12 to ≤24 kg) for 14 days.
The double-blind IP will be based on 5 weight bands:
- 6 to ≤9 kg: ticagrelor 5 mg or matching placebo, twice a day
- >9 to ≤12 kg: ticagrelor 10 mg or matching placebo, twice a day
- >12 to ≤24 kg: ticagrelor 15 mg or matching placebo, twice a day
- >24 to ≤48 kg: ticagrelor 30 mg or matching placebo, twice a day
- >48 kg: ticagrelor 45 mg or matching placebo, twice a day
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor | Experimental | The double-blinded study drug dose will be weight dependent. Receives: Drug: Brilinta |
| Placebo | Placebo comparator | The double-blinded study drug dose will be weight dependent Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Vaso-Occlusive Crises
Vaso-occlusive crises (VOC) defined as the composite of a painful crisis and/or an Acute Chest Syndrome (ACS) . Each component is defined as:
A painful crisis is an onset or worsening of pain that lasts at least 2 hours, for which there is no explanation other than vaso-occlusion and which requires therapy with oral or parenteral opioids, parenteral NSAIDs, or other analgesics prescribed by a health care provider in a medical setting (such as a hospital, clinic or emergency room visit) or at home.
An ACS is an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray.
Measured: Up to end of study visit (12 to 24 months)
Secondary outcomes (16)
Number of Vaso-Occlusive Crises in patients aged 2 to <18 years
Measured: Up to end of study visit (12 to 24 months)
Number of painful crises
Measured: Up to end of study visit (12 to 24 months)
Number of Acute Chest Syndromes
Measured: Up to end of study visit (12 to 24 months)
Duration of painful crises
Measured: Up to end of study visit (12 to 24 months)
Number of Vaso-Occlusive Crises requiring hospitalisation or emergency department visits
Measured: Up to end of study visit (12 to 24 months)
Number of days hospitalised for Vaso-Occlusive Crises
Measured: Up to end of study visit (12 to 24 months)
Number of acute Sickle Cell Disease complications
Measured: Up to end of study visit (12 to 24 months)
Number of days hospitalised for acute Sickle Cell Disease complications
Measured: Up to end of study visit (12 to 24 months)
Number of sickle cell-related red blood cell (RBC) transfusions
Measured: Up to end of study visit (12 to 24 months)
Health-related quality of life (HRQL)
HRQL total score and by dimension using Paediatric Quality of Life Inventory (PedsQL) Sickle Cell Disease 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)
Measured: At randomization, visit 9 (6 months), visit 15 (12 months), visit 21 (18 months) and End of Study visit (12 to 24 months).
Absence from school or work due to Sickle Cell Disease
Proportion of days of absence from school or work (only if going to school or work at randomisation)
Measured: Up to end of study visit (12 to 24 months)
Intensity of pain during Vaso-Occlusive Crises in patients aged ≤4 years
Intensity of worst pain daily during Vaso-Occlusive Crises
- For patients aged ≤4 years, observer reported using the Face, Legs, Activity, Cry, Consolability (FLACC) scale
Measured: Up to end of study visit (12 to 24 months)
Intensity of pain during Vaso-Occlusive Crises for patients aged 5 to <18 years
Intensity of worst pain daily during Vaso-Occlusive Crises
- For patients aged 5 to <18 years, self-reported using the Faces Pain Scale - Revised (FPS-R)
Measured: Up to end of study visit (12 to 24 months)
Type of analgesics (opioid and non-opioid) use
Measured: Up to end of study visit (12 to 24 months)
Palatability and Swallowability
For patients aged ≤4 years taking the tablet dispersed or whole, an observer assessment of palatability will be undertaken
Measured: Immediately after administration of IP at randomization and visit 9 (6 months)
Palatability and Swallowabilty
For patients aged ≥5 years taking the tablet dispersed or whole, palatability will be assessed and categorised using the Facial Hedonic Scale
Measured: Immediately after administration of IP at randomization and visit 9 (6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2020
- Study start30 Jun 2020 (estimated)
- Primary completion10 Oct 2022 (estimated)
- Study completion10 Oct 2022 (estimated)
Why it stopped: Study halted prematurely, prior to enrolment of first patient.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Responsible party
- Sponsor
- Investigators
- Anders Berggren, MD, PhD, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04293172
- Sponsor's protocol ID
- D5136C00013
- Acronym
- HESTIA5
- Status last verified
- Jul 2020
- First submitted
- 4 Feb 2020
- Last updated
- 15 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04293172
- Acronym / sponsor ID
- HESTIA5 / D5136C00013
- Conditions
- Sickle Cell Disease
- Keywords
- Ticagrelor, Vaso-Occlusive Crises, Paediatric Patients, 6 Months to <18 Years, Sickle Cell Disease, Sickle Cell Anemia, Platelet aggregation, Brillinta
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study halted prematurely, prior to enrolment of first patient.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Study start
- 30 Jun 2020 (estimated)
- Primary completion
- 10 Oct 2022 (estimated)
- Study completion
- 10 Oct 2022 (estimated)
- First posted
- 3 Mar 2020 (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.
The purpose of this study is to compare the effect of ticagrelor vs placebo for the reduction of Vaso-Occlusive crises in paediatric patients with Sickle Cell Disease
Detailed description
- HESTIA5 will evaluate the efficacy, safety and tolerability of ticagrelor versus placebo in children with SICKLE CELL DISEASE during treatment for at least 12 months and up to a maximum of 24 months.
- The target population are children (males and females) aged 6 months to <18 years and body weight ≥6 kg diagnosed with homozygous sickle cell or sickle beta-zero-thalassaemia confirmed by high-performance liquid chromatography or hemoglobin electrophoresis. The aim is to randomise 20 patients in the age group 6 to <24 months. At least 50 patients should be randomised in each of the age groups: ≥2 to <12 years and ≥12 to <18 years.
- Prior to randomisation in this study, patients aged 6 to <24 months will undergo a 14-day Run in period in which they will receive open-label ticagrelor twice a day for 14 days according to weight. Run-in period includes 4 visits, called R1, R2, R3 and R4. The run-In period is to ensure that the treatment is well-tolerated, and that the exposure is in line with model-based predictions following repeated twice a day dosing with ticagrelor in this age group. At the end of the Run-in period (Visit R4), the patient will take his/her final dose of open-label IP and await the independent Data Monitoring Committee chairman's evaluation of tolerability, safety and exposure before being eligible to enter the Screening period for randomisation. Patients who complete the Run-in period according to the protocol must also meet all the inclusion/exclusion criteria detailed in Protocol, to proceed to randomisation.
- To be eligible for the study, patients must have experienced at least 2 VASO-OCCLUSIVE CRISES (defined as painful crisis and/or ACUTE CHEST SYNDROME) events in the past 12 months prior to Visit 1, (patients aged 2 to <18 years) and prior to visit R1 (patients aged 6 to <24 months) indicating that the severity of the patient's disease justifies preventive chronic long-term treatment. Even if painful VASO-OCCLUSIVE CRISES are uncommon in infants and become more frequent in older children, data show that symptoms like dactylitis precede more severe events and confirm that children who have early dactylitis are more likely to have severe events later in life.
- Study participants should receive standard of care for SICKLE CELL DISEASE, adjusted to the individual patient at the discretion of the investigator, including routine health care screening examinations and immunizations to local guidelines and health care programmes. Study drug will be given on the background of standard treatments for SICKLE CELL DISEASE. Study participants are not withheld from any other treatments that may be used in SICKLE CELL DISEASE (eg., hydroxyurea) during the trial, which is important considering the use of a placebo control group. However, restrictions apply to some medications and interventions that may be necessary for the patient's health and well-being during the study.
- Patients are to be followed until a common study end date (CSED) is reached defined as 12 months after the last patient is randomized. Treatment duration is at least 12 months for study participants, and patients will continue on treatment until 12 months after last randomized patient or up to a maximum of 24 months. The expected average follow-up is 18 months, assuming a uniformly distributed enrolment period of 12 months. Considering inclusion of patients with at least 2 VASO-OCCLUSIVE CRISES in the past year, this treatment duration is considered long enough to evaluate effects on VASO-OCCLUSIVE CRISES events as well as to capture safety and tolerability data supporting a potential future long term use of ticagrelor.
- Due to ticagrelor mechanism of action and the potential to reduce symptoms caused by ischemia during a vaso-occlusion, a composite endpoint with painful crises and/or ACUTE CHEST SYNDROME has been selected for the primary endpoint. Painful crisis is the most common reason for emergency department visits for patients with SICKLE CELL DISEASE with a significant impact on young patients' lives, affecting them physically and emotionally. Secondary endpoints are included to broaden the understanding of effects in patients with SICKLE CELL DISEASE and to also assess potential benefits on symptomatic disease burden and health-related quality of life (HRQL).
- Patients will be treated with 5, 10, 15, 30 and 45 mg twice a day or matching placebo, depending on body weight.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor | Experimental | Drug: BrilintaThe double-blinded study drug dose will be weight dependent. |
| Placebo | Placebo comparator | Drug: PlaceboThe double-blinded study drug dose will be weight dependent |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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).
- Children aged 6 months to <18 years of age and body weight ≥6 kg diagnosed with HbSS or HbS/β0 as confirmed by high-performance liquid chromatography (HPLC) or haemoglobin electrophoresis.
- Have experienced at least 2 VASO-OCCLUSIVE CRISES (painful crisis and/or ACUTE CHEST SYNDROME) 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 VASO-OCCLUSIVE CRISES need to be documented in the patient's medical records or in other documents that can be reconciled.
- If aged 2 to ≤16 years, must have had a TCD within the past year prior to Visit 2. If this is not the case, a TCD examination must be done before randomisation.
- If aged ≥10 years, must have had an ophthalmological examination within the past year prior to Visit 1. 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.
Key exclusion criteria (21 listed)
- 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.
- 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.
- 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.
- Pathological finding on any other imaging assay indicating increased risk for intracerebral bleeding or thromboembolism.
- International normalised ratio (INR) >1.4 or active pathological bleeding or increased risk of bleeding complications according to Investigator.
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 |
|---|---|---|
| BrilintaPatients in the open-label Run-in period (patients aged 6 to <24 months only) will receive ticagrelor 5 mg twice a day (body weight 6 to ≤9 kg), 10 mg twice a day (body weight >9 to ≤12 kg) or 15 mg twice a day (body weight >12 to ≤24 kg) for 14 days. The double-blind IP will be based on 5 weight bands: * 6 to ≤9 kg: ticagrelor 5 mg or matching placebo, twice a day * >9 to ≤12 kg: ticagrelor 10 mg or matching placebo, twice a day * >12 to ≤24 kg: ticagrelor 15 mg or matching placebo, twice a day * >24 to ≤48 kg: ticagrelor 30 mg or matching placebo, twice a day * >48 kg: ticagrelor 45 mg or matching placebo, twice a day | Drug | Ticagrelor |
| PlaceboPatients in the open-label Run-in period (patients aged 6 to <24 months only) will receive ticagrelor 5 mg twice a day (body weight 6 to ≤9 kg), 10 mg twice a day (body weight >9 to ≤12 kg) or 15 mg twice a day (body weight >12 to ≤24 kg) for 14 days. The double-blind IP will be based on 5 weight bands: * 6 to ≤9 kg: ticagrelor 5 mg or matching placebo, twice a day * >9 to ≤12 kg: ticagrelor 10 mg or matching placebo, twice a day * >12 to ≤24 kg: ticagrelor 15 mg or matching placebo, twice a day * >24 to ≤48 kg: ticagrelor 30 mg or matching placebo, twice a day * >48 kg: ticagrelor 45 mg or matching placebo, twice a day | Drug | Placebo |
Primary outcome
Number of Vaso-Occlusive Crises
Time frame: Up to end of study visit (12 to 24 months)
Vaso-occlusive crises (VOC) defined as the composite of a painful crisis and/or an Acute Chest Syndrome (ACS) . Each component is defined as: A painful crisis is an onset or worsening of pain that lasts at least 2 hours, for which there is no explanation other than vaso-occlusion and which requires therapy with oral or parenteral opioids, parenteral NSAIDs, or other analgesics prescribed by a health care provider in a medical setting (such as a hospital, clinic or emergency room visit) or at home. An ACS is an acute illness characterized by fever and/or respiratory symptoms, accompanied by a new pulmonary infiltrate on a chest X-ray.
16 secondary outcomes
Number of Vaso-Occlusive Crises in patients aged 2 to <18 years
Time frame: Up to end of study visit (12 to 24 months)
Number of painful crises
Time frame: Up to end of study visit (12 to 24 months)
Number of Acute Chest Syndromes
Time frame: Up to end of study visit (12 to 24 months)
Duration of painful crises
Time frame: Up to end of study visit (12 to 24 months)
Number of Vaso-Occlusive Crises requiring hospitalisation or emergency department visits
Time frame: Up to end of study visit (12 to 24 months)
Number of days hospitalised for Vaso-Occlusive Crises
Time frame: Up to end of study visit (12 to 24 months)
Number of acute Sickle Cell Disease complications
Time frame: Up to end of study visit (12 to 24 months)
Number of days hospitalised for acute Sickle Cell Disease complications
Time frame: Up to end of study visit (12 to 24 months)
Number of sickle cell-related red blood cell (RBC) transfusions
Time frame: Up to end of study visit (12 to 24 months)
Health-related quality of life (HRQL)
Time frame: At randomization, visit 9 (6 months), visit 15 (12 months), visit 21 (18 months) and End of Study visit (12 to 24 months).
Absence from school or work due to Sickle Cell Disease
Time frame: Up to end of study visit (12 to 24 months)
Intensity of pain during Vaso-Occlusive Crises in patients aged ≤4 years
Time frame: Up to end of study visit (12 to 24 months)
Intensity of pain during Vaso-Occlusive Crises for patients aged 5 to <18 years
Time frame: Up to end of study visit (12 to 24 months)
Type of analgesics (opioid and non-opioid) use
Time frame: Up to end of study visit (12 to 24 months)
Palatability and Swallowability
Time frame: Immediately after administration of IP at randomization and visit 9 (6 months)
Palatability and Swallowabilty
Time frame: Immediately after administration of IP at randomization and visit 9 (6 months)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
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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. This study is not recruiting at the moment.
Anders Berggren, MD, PhD study director
AstraZeneca
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brilinta in people with Sickle Cell Disease, run by AstraZeneca.
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 9 inclusion and 21 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: withdrawn, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Vaso-Occlusive Crises (time frame: Up to end of study visit (12 to 24 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2020.