Malaria
Conditions
Interventions
Sponsors
Liverpool School of Tropical Medicine
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: • =2 weeks and <14 weeks (13-6/7 weeks inclusive) gestation from the last menstrual period (LMP) as assessed by echography • Microscopy confirmed P. falciparum mono or mixed infections, regardless of symptoms. • Emancipated minor and aged =16 years • Haemoglobin = 7 g/dL • Residence within the health facility catchment area • Willingness to adhere to study requirements and to deliver the baby at the local health facility • Ability to provide written informed consent
Exclusion criteria
Exclusion criteria: • Known allergy to any of the study drugs • History of known pregnancy complications or poor obstetric history, such as repeated miscarriages, stillbirths, or eclampsia • History or presence of major illnesses likely to influence pregnancy outcome; • Known HIV positive • Any significant illness at the time of screening requiring hospitalisation, including severe malaria • Intent to move out of the study catchment area before delivery or planned delivery out of the catchment area • Recent (2 weeks) treatment with antimalarials or antimicrobials with antimalarial activity (chloroquine, AL, DP, PA, SPAQ, ASAQ, MQAS, azithromycin, clindamycin, tetracycline, quinolones, cotrimoxazole and SP) • Twin/multiple pregnancy detected • Non-viable pregnancy confirmed by ultrasound or doppler • Known history or evidence of clinically significant cardiovascular disorders or family history of sudden death or congenital long QT syndrome or current co-administration of other drugs that might contribute to a prolonged QTc interval or cause “Torsades de Point” • Chronic medical condition requiring frequent medications (e.g., TB, suspected hepatic lesions, liver disease, sickle cell disease, diabetes, epilepsy, asthma and hypertension) • Prior randomisation in this study during the current pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary efficacy endpoint •PCR-adjusted adequate clinical and parasitological response (ACPR) by Day 42 ;Key safety endpoint •A composite endpoint of miscarriage, stillbirth, or major congenital anomalies. | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse events and serious adverse events (SAEs) incidence and severity, including significant changes in relevant laboratory values;Drug discontinuation due to adverse drug reactions at any time during pregnancy. ;Gestational age at delivery, birthweight, Z-scores for birthweight for gestational age, and their binary versions (preterm birth [PTD], low birth weight [LBW], and small-for-gestational age [SGA]) and neonatal death;Vulnerable newborn: the composite of LBW, PTD or SGA among live births.;Adverse pregnancy outcome: a composite of miscarriage, stillbirth, major congenital anomalies, vulnerable newborn (PTB/LBW/SGA) or neonatal deaths ;PCR-adjusted ACPR by Day 28;PCR-unadjusted ACPR rate by Day 28 and 42 (i.e, no treatment failure or new infection);Survival analysis over 42 days for recurrent, recrudescent and new infections;Fever clearance by Day 3;Parasite clearance by Day 3, including sub-microscopic malaria infection;Gametocyte carriage and clearance;Proportion anaemic and mean haemoglobin on Days 14, 28 and 42 and at delivery;Prevalence of placenta malaria at delivery (active infection).;PK parameters such as Cmax, AUC, and T1/2 wherever possible;Neurodevelopment score from infants at 3 and 6 months using Bayley Scales of Infant and Toddler Development;Incidence of developmental delays or abnormalities detected during routine paediatric exams in the first 6 months of life.;Attainment of key developmental milestones, assessed at 3 and 6 months;Parent questionnaires on infant temperament, sleep patterns, and behavioural development at 3 and 6 months | — |
Countries
Burkina Faso, Kenya, Mali
Contacts
Public ContactDr Hellen Barsosio
principal investigators
Outcome results
None listed