Haematological Disorders Malaria Bacterial infection Paediatrics
Conditions
Interventions
Sponsors
Imperial College
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? 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
Exclusion criteria
Exclusion criteria: ? Weighing 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ?R1: mortality (all-cause) ?R2: malaria-associated hospitalisations (diagnosed by rapid diagnostic test (RDT) and confirmed by microscopy and/or PCR) ?R3: hospitalisation for any reason | — |
Secondary
| Measure | Time frame |
|---|---|
| ? Mortality (where mortality is not the primary outcome for that randomisation) ? Malaria-associated hospitalisations (where not the primary outcome) ? All-cause hospitalisations (where not the primary outcome) ? 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 ? Number of blood transfusions and volume of blood transfused ? Haemoglobin (Hb) and fetal haemoglobin (HbF) concentrations ? The frequencies of abnormal renal or liver function test result ? Febrile events treated with intravenous antibiotics ? Specific bacterial bloodstream infections confirmed by blood culture or molecular typing ? Serious adverse events (SAEs) | — |
Countries
Uganda
Contacts
Public ContactDenis Aromut
Trial Manager
Outcome results
None listed