Primaquine in African Children: PAC study
| ISRCTN | ISRCTN11594437 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11594437 |
| Protocol serial number | BAKMAL1606, 106698/Z/14/Z |
| Sponsor | The University of Oxford |
| Funder | DFID/MRC/Wellcome Trust |
- Submission date
- 17/03/2017
- Registration date
- 09/05/2017
- Last edited
- 20/10/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Malaria is a disease that is spread by mosquito bites. It causes flu-like symptoms but can also cause serious illness and death. Malaria is a major problem in tropical areas like Africa. Research has shown that a drug called primaquine can reduce the malaria offspring in mosquitos which can then reduce malaria transmission. However, primaquine has a major disadvantage as it changes to act like bleach in the body. This is problematic to people who have naturally weak red blood cells and are lacking an enzyme that makes the chemicals that counteract bleach and drug metabolites called glucose 6 phosphate dehydrogenase (G6PD). The less G6PD in the red cells, the more damaging primaquine's is. It can cause red cells may burst open (haemolysis) which creates many health problems. Many malaria control programmes are unwilling to use primaquine because they think it is too dangerous and they cannot afford the cost, training or equipment to test for G6PD levels. Although the World Health Organisation (WHO) recommends using low dose primaquine even in malaria patients with G6PD deficiency, primaquine is not being used due to a lack of research, concerns about tests for G6PD and issues providing the medication to children. The aim of this study is to provide evidence that a low dose of primaquine is safe in G6PD deficient kids in order to reduce malaria rates and benefit communities.
Who can participate?
Children aged six months to 11 years old who have malaria.
What does the study involve?
Participants are allocated to one of two groups. Those in the first group have a deficiency in G6PD and those in the second group have normal G6PD levels. Participants in each group are then randomly allocated to one of four dosing treatments which include primaquine and combination treatments and two placebo primaquine treatment. The doses vary with each participant’s age and weight and are given daily for three days. The placebo group only receives the medication once. Participants are followed up for 42 days to measure their iron deficiency level in their blood.
What are the possible benefits and risks of participating?
Participants may benefit from knowing the status of their G6PD levels and from receiving information and counseling. There are risks with primaquine as it can cause anaemia (low blood iron).
Where is the study run from?
1. Kinshasa Mahidol Oxford Tropical Medicine Research Unit (Democratic Republic of Congo)
2. The Mbale Regional Referral Hospital (Uganda)
When is the study starting and how long is it expected to run for?
Feburary 2017 to November 2020
Who is funding the study?
DFID/MRC/Wellcome Trust (UK), grant reference number: MR/P006973/1
Who is the main contact?
Dr Bob Taylor
Contact information
Public
Mahidol Oxford Tropical Medicine Clinical Research Unit (MORU)
Mahidol University
420/6 Rajvithi Road
Rajthevee
Bangkok
10400
Thailand
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multi-centre double-blind open randomized parallel safety trial |
| Secondary study design | Randomised parallel trial |
| Participant information sheet | ISRCTN11594437_PIS_14Feb17_V2_Uganda.pdf |
| 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 |
| Study acronym | PAC study |
| Study objectives | The aim of this study is to provide evidence for drug policy on the safety of the WHO recommended SLDPQ regimen when used under close to routine conditions to G6PDd African children with acute uncomplicated P. falciparum. |
| Ethics approval(s) | Oxford Tropical Research Ethics Committee, 01/03/2017, ref: 53-16 |
| Health condition(s) or problem(s) studied | Uncomplicated falciparum Malaria, G6PD deficiency, Single low dose primaquine (SLDPQ) |
| Intervention | 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. |
| Intervention type | Drug |
| Phase | Phase III/IV |
| Drug / device / biological / vaccine name(s) | Artemether, lumefantrine, dihydroartemisinin, piperaquine, primaquine |
| Primary outcome measure(s) |
1. Profound anaemia (Hb concentration < 4g/dL) is measured using the HemoCue machine during the first days 21 days of follow up |
| Key secondary outcome measure(s) |
1. Fractional change in haemoglobin on day seven vs. baseline, measured by HemoCue® at baseline and day seven |
| Completion date | 02/11/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Months |
| Upper age limit | 11 Years |
| Sex | All |
| Target sample size at registration | 1600 |
| Total final enrolment | 1137 |
| Key inclusion criteria | 1. Aged 6 months to 11 years old 2. Clinically uncomplicated disease 3. Fever (≥37.5⁰C 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 |
| Key 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 |
| Date of first enrolment | 17/07/2017 |
| Date of final enrolment | 07/10/2019 |
Locations
Countries of recruitment
- Congo, Democratic Republic
- Uganda
Study participating centres
University of Kinshasa
Avenue Tombalbaye 68-78
Kinshasa
1015
Congo, Democratic Republic
Mbale Regional Referral & Teaching Hospital
Mbale
209
Uganda
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 30/11/2022 | 05/12/2022 | Yes | No | |
| Results article | 20/10/2023 | 20/10/2023 | Yes | No | |
| Results article | 01/07/2025 | 02/07/2025 | Yes | No | |
| Results article | Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo | 15/10/2025 | 20/10/2025 | Yes | No |
| Other publications | Age-based dosing regimen development | 18/01/2018 | 21/10/2021 | Yes | No |
| Other publications | Pharmacokinetics | 25/09/2023 | 09/06/2025 | Yes | No |
| Participant information sheet | version V2 | 14/02/2017 | 01/06/2017 | No | Yes |
| Participant information sheet | version V2 | 14/02/2017 | 01/06/2017 | No | Yes |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Protocol file | version 2 | 01/09/2018 | 22/08/2022 | No | No |
Additional files
- ISRCTN11594437_PIS_14Feb17_V2_Uganda.pdf
- Uploaded 01/06/2017
- ISRCTN11594437_PIS_14Feb17_V2.pdf
- Uploaded 01/06/2017
- ISRCTN11594437_PROTOCOL_V2_01Sep18.pdf
- Protocol file
Editorial Notes
20/10/2025: Publication reference added.
02/07/2025: Publication reference added.
09/06/2025: Publication reference added.
20/10/2023: Publication reference added.
05/12/2022: Publication reference added.
22/08/2022: Protocol file uploaded.
15/08/2022: The intention to publish date has been changed from 01/02/2022 to 01/10/2022.
21/02/2022: The recruitment start date was changed from 01/09/2017 to 17/07/2017.
21/12/2021: The intention to publish date was changed from 01/11/2021 to 01/02/2022.
21/10/2021: Publication reference added.
03/08/2021: The intention to publish date was changed from 01/08/2021 to 01/11/2021.
06/05/2021: The intention to publish date was changed from 01/05/2021 to 01/08/2021.
09/12/2020: The following changes were made to the trial record:
1. The overall end date was changed from 19/11/2019 to 02/11/2020.
2. The intention to publish date was changed from 01/12/2020 to 01/05/2021.
3. The plain English summary was updated to reflect these changes.
23/09/2020: Internal review.
06/08/2020: The following changes were made to the trial record:
1. The overall end date was changed from 01/06/2020 to 19/11/2019.
2. The total final enrolment was added.
3. The recruitment end date was changed from 31/12/2019 to 07/10/2019.
4. The participant level data was changed from "Not provided at time of registration" to "Available on request"
5. The publication and dissemination plan was changed.
6. The plain English summary was updated to reflect these changes.
10/09/2018: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/07/2018 to 31/12/2019.
2. The overall trial end date was changed from 01/03/2019 to 01/06/2020.
3. The intention to publish date was changed from 31/07/2019 to 01/12/2020.
01/06/2017: Participant information sheet uploaded.
