Sickle cell disease Circulatory System Sickle cell disease
Conditions
Interventions
Current interventions as of 27/02/2024:
H-PRIME will recruit children between the ages of 1-10 years and follow them over a maximum period of 48 months. Children in different randomisations will be fo
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 1-10 years inclusive 2. Confirmed Sickle Cell Disease (SCD) (diagnosed either by HPLC or IEF at a qualified laboratory) 3. Have received conjugate pneumococcal vaccination against Hib and S. pneumoniae (otherwise eligible but unvaccinated children will be vaccinated through the study) 4. 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: 1. Already meet criteria for starting hydroxyurea under Uganda National Guidelines 2026 (frequent crises (>5/year), abnormal transcranial Doppler ultrasound velocities, stroke or acute chest syndrome) 2. Already receiving hydroxyurea 3. 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) 4. Known cancer 5. A clinical history of previous or existing liver or renal diseases unrelated to sickle cell disease 6. Known cardiac ventricular dysfunction or failure or a previous history of cardiac arrhythmias 7. 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)) 8. Current participation in any other clinical trial of an investigational medicinal product 9. 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 |
|---|---|
| Determined either at the time they occur, via direct communication from participants to the study team, or at each of the 3 monthly followup appointments: Group 1: Mortality Group 2: Malaria-associated hospitalisations (diagnosed by rapid diagnostic test (RDT) and confirmed by microscopy and/or PCR) Group 3: Hospitalisations for any reason | — |
Secondary
| Measure | Time frame |
|---|---|
| Determined either at the time they occur, via direct communication from participants to the study team, or at each of the 3 monthly followup appointments: 1. Mortality (for both randomisations in which mortality is not the primary outcome - G2 and G3) 2. Malaria-associated hospitalisations (where not the primary outcome - G1 and G3) 3. All-cause hospitalisations (where not the primary outcome - G1 and G2) 4. Any of the following specific SCD-specific complications requiring medical intervention (Grade 2 or above): painful crisis, hand-foot syndrome, splenic sequestration, acute chest syndrome or stroke. | — |
Countries
Uganda
Contacts
Public ContactDennis Amorut
Outcome results
None listed