Primaquine in African Children: PAC study

• Register: ISRCTN
• Last refreshed on: 30 October 2023
• Main ID: ISRCTN11594437
• Date of registration: 09/05/2017
• Prospective Registration: Yes
• Primary sponsor: The University of Oxford
• Public title: Primaquine in African Children: PAC study
• Scientific title: Assessing the tolerability and safety of single low dose primaquine in African children with acute uncomplicated falciparum malaria and glucose 6 phosphate dehydrogenase deficiency in Africa
• Date of first enrolment: 17/07/2017
• Target sample size: 1600
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN11594437
• Study type: Interventional
• Study design: Multi-centre double blind open randomised parallel safety trial (Treatment)
• Phase: Phase III/IV

Countries of recruitment

Congo, Democratic Republic, Uganda

Contacts

• Name: Bob Taylor

Key inclusion & exclusion criteria

Inclusion criteria: 1. Aged six months to 11 years old
2. Clinically uncomplicated disease
3. Fever (= 37.5°C aural) or history of fever within the previous 72 hours
4. Positive malaria RDT (Uganda only)
5. Positive malaria slide for P. falciparum (mono or mixed infection) of any parasitaemia (Kinshasa only)
6. Informed consent provided by patient or relative/legal guardian
Exclusion criteria: 1. Malaria danger signs, sign(s) of severe malaria, or decompensated anaemia, including: an inability to take or retain fluids or oral medications, confusion, prostration, convulsions, respiratory distress, passing of red or cola-coloured urine (putative “blackwater fever”)
2. Severe anaemia (Hb <6 g/dL)
3. Comorbid illness that requires treatment in hospital (physician’s judgement)
4. Patients on drugs known to cause haemolysis in G6PDd e.g. dapsone, nalidixic acid
5. Known to be allergic to PQ, AL, or DHAPP
6. Previous enrolment in the current trial or current enrolment in another trial

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Uncomplicated falciparum Malaria, G6PD deficiency, Single low dose primaquine (SLDPQ)
Infections and Infestations
Uncomplicated falciparum Malaria, G6PD deficiency, Single low dose primaquine (SLDPQ)

Intervention(s)

Participants are allocated to either the G6PDd group or the G6PD normal group based on their the results of a G6PD rapid diagnostic test (RDT).

Participants are then randomly allocated as to which dosing group they receive using a computer generated randomisation list generated for each site. Treatment allocation is placed in a sealed envelope which is opened once participants receive their study number. The treatment allocation described the Artemisinin based combination treatment (ACT) to be given and the number of PQ/placebo pack.

The four dosing groups are the following:
1. Artemether Lumefantrine (AL) + single low-dose primaquine (SLDPQ)
2. Artemether Lumefantrine (AL) + single low-dose primaquine (SLDPQ) placebo
3. Dihydroartemisinin-piperaquine (DHAPP) + single low-dose primaquine (SLDPQ)
4. Dihydroartemisinin-piperaquine (DHAPP) + single low-dose primaquine (SLDPQ) placebo

The dosages for primaquine depends vary with age and the dosing for AL vary with weight (in kg). DHAPP+SLDPQ dosages are given daily for three days and vary with body weight (in kg). Those who receive the primaquine/placebo receive it once only at baseline. Follow up continues until day 42.

Primary Outcome(s)

1. Profound anaemia (Hb concentration < 4g/dL) is measured using the HemoCue machine during the first days 21 days of follow up
2. Severe anaemia (Hb <5g/dL) with clinical features of severe malaria is measured using the HemoCue machine during the first 21 days of follow up

Secondary Outcome(s)

1. Fractional change in haemoglobin on day seven vs. baseline, measured by HemoCue® at baseline and day seven
2. Proportion of patients with a fractional change of = 25% measured by HemoCue® over the follow up period of 42 days
3. Determinants of changes in HemoCue® measured haemoglobin over the follow up period of 42 days
4. G6PD genotype (hemizygous male, homo-, heterozygous female, normal) and selected G6PD variants (e.g. G6PD A- 202 mutations) are assessed by polymerase chain reaction (PCR) at baseline
5. G6PD enzyme activity is measured using a quantitative spectrophotometric method at baseline
6. Genotypes of other inherited blood disorders are assessed by polymerase chain reaction (PCR) at baseline
7. Incidence of adverse events are measured using clinical and laboratory records over the follow up period of 42 days
8. Pharmacokinetic characteristics of PQ and carboxyPQ by measuring drug concentrations at baseline and at hours one, one and a half, two, three, four, six, eight, ten, 12, 24 hours
9. Pharmacokinetic characteristics of lumefantrine and piperaquine are measured using their drug concentrations at baseline, day three, seven and 28
10. CYP 2D6 genotypes are assessed by polymerase chain reaction (PCR) at baseline
11. Asexual parasitaemia clearance time and half life are measured using malaria slide results at days one, two and three
12. Therapeutic efficacy of AL and DHAPP is measured using the WHO criteria at day 42
13. Gametocytaemia over time is measured using thick blood films at baseline and days one, two, three, seven, 14, 21, 28, 35 and 42
14. Proportion of patients with gametocytes over time is measured using those with a positive thick blood film at baseline and on days one, two, three, seven, 14, 21, 28, 35 and 42

Secondary ID(s)

BAKMAL1606, 106698/Z/14/Z

Source(s) of Monetary Support

DFID/MRC/Wellcome Trust

Ethics review

Status:
Approval date:
Contact:

Old ethics approval format; Oxford Tropical Research Ethics Committee, 01/03/2017, ref: 53-16

Results

• Results available: Yes
• Date Completed: 02/11/2020