Acute uncomplicated Plasmodium falciparum malaria Infections and Infestations Plasmodium falciparum malaria
Conditions
Interventions
Current intervention as of 28/06/2022:
Anti-infectivity study
This is an open, randomised, parallel, phase IIb trial assessing the anti-infectivity efficacy, tolerability and PK of single low-dose pri
thereafter, tablets will be used
2. ASPYR + SLDPQ (allometrically scaled weight-based regimen)
Acceptability study
This will be done using the ClinSearch Acceptability Score Test (CAST®) and then cal
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant parent/legal guardian is willing and able to give informed consent for participation in the study 2. Aged =6 months and <5 years 3. Weight =5 kg 4. Presentation with fever (axillary =37.5°C, tympanic =38°C) or fever history =24 h and clinically uncomplicated disease 5. P. falciparum parasitaemia 1,000 – 250,000/µl (mono-/mixed Plasmodium species) detected by light microscopy 6. Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule
Exclusion criteria
Exclusion criteria: 1. General danger signs in children under 5 years or signs of severe falciparum malaria according to the definitions of WHO (2000) e.g. prostration, respiratory distress, reduced consciousness 2. Persistent vomiting as given in the history of the current illness 3. P. falciparum (Pf) parasitaemia >250,000/µl (>5% parasitaemia) 4. Haemoglobin (Hb) <5 g/dl 5. Patients on treatment for a significant illness e.g. HIV/AIDS, TB, leprosy or currently taking a drug known to cause haemolysis in G6PDd 6. Known to be allergic to PQ or ASPYR 7. On regular medication, which might interfere with antimalarial pharmacokinetics 8. Antimalarials taken within the last 2 weeks 9. Having taken a herbal medicine within the last 4 weeks 10. Previous participation in a malaria vaccine trial 11. Previous enrolment in the current trial or current enrolment in another trial 12. Severe malnutrition – defined as a mid-upper arm circumference (MUAC) <115 mm 13. Febrile condition due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal or hepatic diseases, HIV/AIDS)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 28/06/2022: 1. Proportions of patients infecting =1 mosquito in the ASPYR arm vs ASPYR+SLDPQ arm assessed by direct membrane feeding on days 0, 1, 2, and 7 2. Mean within-person percentage change in mosquito infectivity assessed by direct membrane feeding at baseline and on days 1, 2, 7, and 14 Previous primary outcome measure: 1. Proportions of patients infecting =1 mosquito in the ASPYR arm vs ASPYR+SLDPQ arm assessed by direct membrane feeding at days 2, 3, 7 and 14 2. Mean within-person percentage change in mosquito infectivity assessed by direct membrane feeding on days 2, 3, 7 and 14 vs baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 28/06/2022: 1. Determine mosquito infectivity by measuring proportion of mosquitoes with detected oocysts and sporozoites, oocyst intensity & sporozoite index on days 0, 1, 2, and 7 2. Gametocyte carriage assessed by quantitative nucleic acid sequence-based amplification and microscopy on days 0, 1, 2, 7, and 14 3. Primaquine exposure and anti-infectivity efficacy measured using pharmacokinetics (PK) on days 0 and 1 and direct membrane feeding assay (DMFA) on days 0, 1, 2, and 7 4. Haemoglobin (Hb) dynamics & recovery by Day 28 measured using a HemoCue® machine on days 0, 1, 2, 3, 7, 14, 21, 28, 35, and 42 5. Presence of sickle cell trait/disease, thalassemia and G6PD variants measured using PCR on day 0 6. Cure rate measured using microscopy of a Giemsa stained thick blood film on day 42 7. Parasite and fever clearance times measured using microscopy and a thermometer respectively on days 0, 1, 2, 3, 7, 14, 21, 28, 35 and 42 8. Tolerability measured using adverse events, methaemoglobin oximeter on day 0, 1, 2, 3, 7, 14, 21, 28, 35, and 42 and biochemistry on days 0 and 7 9. CYP 2D6 polymorphisms measured using PCR on day 0 10. PQ and carboxyPQ PK parameters measured using PK on days 0 and 1 11. Covariates explaining variability in PQ and carboxyPQ PK parameters measured using nonlinear mixed-effects modelling on days 0 and 1 12. Acceptability score measured using the ClinSearch Acceptability Score Test (CAST) on day 0 13. Proportions of patients/careers responding to specific questions on a Knowledge, Attitude and Practices (KAP) questionnaire and the mean values of household income on day 0 Previous secondary outcome measures: 1. Gametocyte carriage assessed by quantitative nucleic acid sequence-based amplification and microscopy at days 0, 3, 7, 14, 28, 35 and 42 2. Primaquine exposure and anti-infectivity efficacy measured using pharmacokinetics (PK) and direct membrane feeding assay (DMFA) at days 0, 1 and days 0, 2, 3 | — |
Countries
Burkina Faso
Outcome results
None listed