Hydroxyurea – Pragmatic Reduction in Mortality and Economic burden: A multi-centre Phase III trial to investigate the efficacy of hydroxyurea for children with sickle cell anaemia when administered in a pragmatic fashion.
- Conditions
- Haematological DisordersMalariaBacterial infectionPaediatrics
- Registration Number
- PACTR202401802272880
- Lead Sponsor
- Imperial College
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 1800
?Aged 1-10 years inclusive
?Confirmed SCD (either by HPLC or IEF at a qualified laboratory)
?Have received conjugate pneumococcal vaccination against Hib and S. pneumoniae (otherwise eligible but unvaccinated children will be vaccinated through the study as above)
?Carer willing/able to provide consent and to bring the child for follow-up visits, as demonstrated by either regular attendance at SCD clinics to date, or attending two visits (one of which may be the screening visit) before randomisation
?Weighing <8kg – temporary exclusion pending the achievement of 8kg or more
?Already meet criteria for starting hydroxyurea in national guidelines (frequent crises (>5/year), known abnormal transcranial Doppler ultrasound velocities, stroke or acute chest syndrome)
?Already receiving hydroxyurea
?Taking concomitant medications that are contraindicated with any of the trial medications (hydroxyurea, SP, DHA-PQP, penicillin V, cotrimoxazole) (including, but not limited to, nefazodone, verapamil, rifampicin, isoniazid, ethambutol)
?A positive pregnancy test at screening or enrolment visits
?Known cancer
?A clinical history of previous or existing liver or renal diseases unrelated to sickle cell disease
?Known cardiac ventricular dysfunction or failure or a previous history of cardiac arrhythmias
?Known HIV (these children should receive cotrimoxazole prophylaxis and many will be receiving antiretrovirals that are contraindicated with one or more trial medications (zidovudine, amprenavir, atazanavir, indinavir, nelfinavir, ritonavir))
?Current participation in any other clinical trial of an investigational medicinal product
?Presence of acute infection on the day of screening (e.g. symptomatic P. falciparum malaria, pneumonia, septicaemia, meningitis, newly identified tuberculosis) – such children may be enrolled after recovery from an acute infection if they do not meet other exclusion criteria
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method ?R1: mortality (all-cause)<br>?R2: malaria-associated hospitalisations (diagnosed by rapid diagnostic test (RDT) and confirmed by microscopy and/or PCR)<br>?R3: hospitalisation for any reason<br><br>
- Secondary Outcome Measures
Name Time Method ?Mortality (where mortality is not the primary outcome for that randomisation)<br>?Malaria-associated hospitalisations (where not the primary outcome)<br>?All-cause hospitalisations (where not the primary outcome)<br>?Any of the following SCD-specific complications requiring medical intervention (Grade 2 or above): painful crisis, hand-foot syndrome, splenic sequestration, acute chest syndrome or stroke <br>?Number of blood transfusions and volume of blood transfused<br>?Haemoglobin (Hb) and fetal haemoglobin (HbF) concentrations<br>?The frequencies of abnormal renal or liver function test result<br>?Febrile events treated with intravenous antibiotics<br>?Specific bacterial bloodstream infections confirmed by blood culture or molecular typing<br>?Serious adverse events (SAEs)