MalariaPhase 4ESSLDPQP4502D6NCT03352843
Single Low-dose Primaquine Efficacy and Safety.
A Phase 4 study testing Primaquine in people with Malaria, run by Tropical Pesticides Research Institute, Tanzania at 1 site in Tanzania.
Trial summary
Background: The World Health Organization has recommended addition of a 0.25 mg/kg single-dose primaquine (PQ) to standard artemisinin-based combination therapy (ACT) for elimination of malaria in low transmission-settings and for containment in areas threatened by artemisinin resistance. Read more about this study
- Who is it for?
- Ages 1 year to 10 years
- Conditions the study is for
- Malaria
- What is being tested?
- Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 1 siteTanzania
- Study dates
- 11 Jun 2019to 28 Feb 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age from 1 to 10 years
- Weight ≥ 10 kg
- Body temperature ≥ 37.5°C or history of fever in the last 24 hours
- Microscopy confirmed P. falciparum mono-infection
- Parasitemia level of 2000 - 200000/µL
- Ability to swallow oral medication
- Ability and willingness to abide by the study protocol and the stipulated follow up visits
- Written proxy informed consent from a parent/guardian.
Who cannot join
- Evidence of severe malaria or danger signs
- Known allergy to trial medicines
- Reported antimalarial intake ≤ 2 weeks
- Hemoglobin < 5 g/dL
- Blood transfusion within last 90 days
- Febrile condition other than malaria
- Known underlying chronic or severe disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Single Low-dose Primaquine Efficacy and Safety for Treatment of Uncomplicated Plasmodium Falciparum Malaria Based on Cytochrome P450 2D6 Activity in Bagamoyo District, Tanzania.
Background: The World Health Organization has recommended addition of a 0.25 mg/kg single-dose primaquine (PQ) to standard artemisinin-based combination therapy (ACT) for elimination of malaria in low transmission-settings and for containment in areas threatened by artemisinin resistance. However, PQ metabolism is dependent on a highly polymorphic cytochrome P450 (CYP) 2D6 isoenzyme which probably compromises the drugs' safety and efficacy, particularly in individuals with reduced isoenzyme activity. This trial therefore, aims to assess the safety and efficacy of 0.25 mg/kg single-dose PQ when added to standard artemether-lumefantrine regimen for clearance and sterilization of Plasmodium falciparum gametocytes in patients with CYP450 2D6 reduced/null activity as compared to those with normal/increased enzyme activity.
Methods: On hundred and fifty-five children aged between 1 and 10 years and with uncomplicated P. falciparum malaria will be enrolled, treated with standard artemether-lumefantrine regimen plus a 0.25 mg/kg single-dose of PQ and then followed up on days 0, 1, 2, 3, 7, 14, 21 and 28 for clinical and laboratory assessment. Primaquine will be administered together with the first dose of artemether-lumefantrine. Safety assessment will be performed using the Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT). Gametocytes will be detected and quantified by microscopy and Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA) on days 0 and 7. For a subset of 100 participants, post-treatment infectiousness will be assessed by mosquito feeding assays on day 7. The CYP2D6 status will be determined using a polymerase chain reaction (PCR) followed by a restriction fragment length polymorphism (RFLP). The primary outcome will be the safety of single low-dose primaquine in patients with CYP2D6 reduced/null compared to those with normal/increased activity.
Expected outcomes: The findings will provide the much-needed information on the safety and efficacy of single low-dose primaquine for clearance and sterilization of P. falciparum gametocytes in individuals with reduced/null compared to those with normal/increased CYP450 2D6 isoenzyme activity prior to the implementation of the treatment policy particularly in Africa.
- Conditions
- Malaria
- Being tested
- Primaquine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrimaquineDrug
All patients will be administered with a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen, and then followed-up for 28 days for clinical and laboratory assessment to assess safety and efficacy.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Not described Receives: Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of single low-dose primaquine.
Proportion of participants with adverse and or serious adverse events between days 0 and 28 of follow up following treatment with a single low-dose primaquine in individuals with reduced/null compared to those with normal/increased CYP450 2D6 isoenzyme activity.
Measured: 6 months after the start of recruitment
Secondary outcomes (2)
Sterilization of gametocytes
Proportion of participants with infected mosquitoes following membrane feeding experiment on day 7.
Measured: 6 months after the start of recruitment
Gametocytes carriage on day 7
Proportion of participants with gametocytes carriage measured by QT-NASBA on day 7
Measured: 12 months after the start of recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2017
- Study start11 Jun 2019
- Primary completion28 Feb 2020
- Study completion28 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tropical Pesticides Research Institute, Tanzania
- Sponsor type
- Other government
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Principal investigator, Richard Mwaiswelo, Tropical Pesticides Research Institute, Tanzania
- Investigators
- Richard O Mwaiswelo, PhD, Principal investigator, Tropical Pesticides Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03352843
- Sponsor's protocol ID
- TMA2016CDF-1555
- Acronym
- ESSLDPQP4502D6
- Status last verified
- Feb 2023
- First submitted
- 9 Nov 2017
- Last updated
- 24 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Shared after the primary findings have been published
Publications
Mwaiswelo RO, Ngasala B, Msolo D, Kweka E, Mmbando BP, Martensson A. A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania. Malar J. 2022 Mar 12;21(1):84. doi: 10.1186/s12936-022-04100-1.
PubMed 35279143
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Low-dose Primaquine Efficacy and Safety for Treatment of Uncomplicated Plasmodium Falciparum Malaria Based on Cytochrome P450 2D6 Activity in Bagamoyo District, Tanzania.
- ClinicalTrials.gov ID
- NCT03352843
- Acronym / sponsor ID
- ESSLDPQP4502D6 / TMA2016CDF-1555
- Conditions
- Malaria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- Tropical Pesticides Research Institute, TanzaniaOther government
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- 11 Jun 2019 (actual)
- Primary completion
- 28 Feb 2020 (actual)
- Study completion
- 28 Feb 2020 (actual)
- First posted
- 24 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: The World Health Organization has recommended addition of a 0.25 mg/kg single-dose primaquine (PQ) to standard artemisinin-based combination therapy (ACT) for elimination of malaria in low transmission-settings and for containment in areas threatened by artemisinin resistance. However, PQ metabolism is dependent on a highly polymorphic cytochrome P450 (CYP) 2D6 isoenzyme which probably compromises the drugs' safety and efficacy, particularly in individuals with reduced isoenzyme activity. This trial therefore, aims to assess the safety and efficacy of 0.25 mg/kg single-dose PQ when added to standard artemether-lumefantrine regimen for clearance and sterilization of Plasmodium falciparum gametocytes in patients with CYP450 2D6 reduced/null activity as compared to those with normal/increased enzyme activity.
Methods: On hundred and fifty-five children aged between 1 and 10 years and with uncomplicated P. falciparum malaria will be enrolled, treated with standard artemether-lumefantrine regimen plus a 0.25 mg/kg single-dose of PQ and then followed up on days 0, 1, 2, 3, 7, 14, 21 and 28 for clinical and laboratory assessment. Primaquine will be administered together with the first dose of artemether-lumefantrine. Safety assessment will be performed using the Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT). Gametocytes will be detected and quantified by microscopy and Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA) on days 0 and 7. For a subset of 100 participants, post-treatment infectiousness will be assessed by mosquito feeding assays on day 7. The CYP2D6 status will be determined using a polymerase chain reaction (PCR) followed by a restriction fragment length polymorphism (RFLP). The primary outcome will be the safety of single low-dose primaquine in patients with CYP2D6 reduced/null compared to those with normal/increased activity.
Expected outcomes: The findings will provide the much-needed information on the safety and efficacy of single low-dose primaquine for clearance and sterilization of P. falciparum gametocytes in individuals with reduced/null compared to those with normal/increased CYP450 2D6 isoenzyme activity prior to the implementation of the treatment policy particularly in Africa.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: Primaquine |
Who may qualify
- Ages
- 1 year to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Age from 1 to 10 years
- Weight ≥ 10 kg
- Body temperature ≥ 37.5°C or history of fever in the last 24 hours
- Microscopy confirmed P. falciparum mono-infection
- Parasitemia level of 2000 - 200000/µL
Key exclusion criteria (7 listed)
- Evidence of severe malaria or danger signs
- Known allergy to trial medicines
- Reported antimalarial intake ≤ 2 weeks
- Hemoglobin < 5 g/dL
- Blood transfusion within last 90 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrimaquineAll patients will be administered with a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen, and then followed-up for 28 days for clinical and laboratory assessment to assess safety and efficacy. | Drug | Single arm |
Primary outcome
Safety of single low-dose primaquine.
Time frame: 6 months after the start of recruitment
Proportion of participants with adverse and or serious adverse events between days 0 and 28 of follow up following treatment with a single low-dose primaquine in individuals with reduced/null compared to those with normal/increased CYP450 2D6 isoenzyme activity.
2 secondary outcomes
Sterilization of gametocytes
Time frame: 6 months after the start of recruitment
Gametocytes carriage on day 7
Time frame: 12 months after the start of recruitment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2023.
- Derived from this study: PubMed 35279143Mwaiswelo RO, Ngasala B, Msolo D, Kweka E, Mmbando BP, Martensson A. A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania. Malar J. 2022 Mar 12;21(1):84. doi: 10.1186/s12936-022-04100-1.
- Individual participant dataSharing planned: Yes. Shared after the primary findings have been published
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard O Mwaiswelo, PhD principal investigator
Tropical Pesticides Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Primaquine in people with Malaria, run by Tropical Pesticides Research Institute, Tanzania at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of single low-dose primaquine. (time frame: 6 months after the start of recruitment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03352843, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2023; AzTrials last refreshed its copy on 31 Oct 2026.