Eziefula 2013

Methods	Individually randomized placebo-controlled, double blind trial conducted December 2011 to March 2013
Participants	468 randomized, aged one to 10 years old, male and female Inclusion criteria: 1. P. falciparum mono infection with parasite density lower than 500,000 parasites/μL 2. Normal G6PD enzyme function 3. Fever or history of fever in past 24 hours
	Exclusion criteria: 1. Signs of severity 2. Haemoglobin concentration < 80 g/L 3. Known allergy to the trial drugs 4. Antimalarials taken within the past two days 5. PQ taken within the past four weeks 6. Blood transfusion within the past 90 days
Interventions	1. AL standard three day (twice per day) course + placebo (given with 5th AL dose, ie, with 1st dose on 3rd day of treatment) 2. AL + 0.1 mg/kg PQ 3. AL + 0.4 mg/kg PQ 4. AL + 0.75 mg/kg PQ (reference)
Outcomes	Primary efficacy: Mean duration of gametocyte carriage Secondary efficacy: Point prevalence of gametocytes on days 7, 10 and 14; gametocyte circulation time (days), AUC of gametocyte density Primary safety: Arithmetic mean maximum decrease in haemoglobin concentration from enrolment to day 28 Secondary safety: Day of haemoglobin nadir, maximum percentage decrease in haemoglobin, percentage of participants with haemoglobin concentration lower than 50 g/L, requirement for blood transfusion, evidence of black urine, and frequency of severe adverse events.
Notes	G6PD enzyme function based on a fluorescence spot test (R&D Diagnostics, Aghia Paraskevi, Greece)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer-generated four-digit treatment assignment codes and allocated these to random dose groups in block sizes of 16.
Allocation concealment (selection bias)	Low risk	Only the pharmacist was aware of allocation.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 8% of patients were lost to follow-up. No group significantly different from others.
Selective reporting (reporting bias)	Low risk	None detected or suspected.
Other bias	Low risk	None detected or suspected.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Masking syrup" added to all treatments to mask taste of drug.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Assessors were blinded.