Table 4.

List of amendment until to date

Amendment number	Protocol version no	Changes
1	V 1.1	• Amendments in response to OXTREC, HREC comments
2	V 2.1 and V 2.2	• Updated visit schedule
3	V 2.11 to V2.15	• Maximum number of symptomatic recurrences limited to 4 then supervised open PQ will be given • Primaquine also to be given supervised for 14 days at the appropriate dose to all participants with at least 1 symptomatic or asymptomatic relapse at the end of the study • Option for telephoning subjects to run though symptom checklist • Patients can be enrolled into the study on the basis of a positive RDT for malaria, as per site local practice • Amend haematological warning signs & management of acute haemolysis
4	V 2.16	• Inclusion of flow cytometry in addition to the currently proposed G6PD tests
5	V 2.16-3.0	• Removal of taking a drug with antimalarial activity during the study as reason to withdraw patient • Add exclusion criterion – cannot be enrolled in IMPROV twice • Exclusion criteria removed: women planning to become pregnant & previous use of antimalarial drugs • G6PD status to be decided on basis of spot test only • Methaemoglobin to be measured at selected sites only and rotated • Assent form amended to include weekly PQ regimen • HemoCue sampling increased in both arms • Maximum number of symptomatic recurrences in Vietnam – 3 within first 6 months – added to the consent form but will be for Vietnam only • Adjustment to dosing table for those weighing 17 kg
6	V 4.0	• Addition of Ethiopia • G6PD substudy with consent form added as an appendix • Study schedule amended accordingly to accommodate additional G6PD testing • Clarity added on PK sampling on D7 & 14 – now to be done pre & post dose
7	V 5.0	• Update list of investigator and affiliations • Remove site in Pakistan and add the 2nd site in Ethiopia • Revise AE reporting to grades 3 and 4 only • Revise management of patients with anemia related adverse events & management of acute haemolysis