MalariaPhase 2/3LOPRIMNCT01935882
Low Dose Primaquine for Clearance of Gametocytes
A Phase 2/3 study testing Artemether-lumefantrine combination, Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine and Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine in people with Malaria and Asymptomatic Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Burkina Faso.
Trial summary
Primaquine (PQ) is currently the only available drug that can clear mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. Read more about this study
- Who is it for?
- Ages 2 to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria, Asymptomatic Malaria, Plasmodium Falciparum
- What is being tested?
- Artemether-lumefantrine combination, Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine and Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 1 siteBurkina Faso
- Study dates
- Sep 2013to Jul 2015
- Phase
- Phase 2/3
- 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 2 to 15 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Age > 2 years and <15 years
- Weight over 10kg
- P. falciparum parasitaemia >1,000 parasites and <200,000 parasites/µl
- P. falciparum gametocytes detected by microscopy
- Normal G6PD enzyme function
- Informed consent by legally acceptable representative
Who cannot join
- Enrolled in another study
- Fever or history of fever in the last 24 hours
- Evidence of severe illness/ danger signs
- Known allergy to study medications
- Hb < 8g/dL
- Started menstruation
Show all 11Show fewer
- Pregnancy or breastfeeding
- Antimalarials taken within the last 2 days
- Primaquine taken within the last 4 weeks
- Blood transfusion within the last 90 days
- Non-falciparum malaria co-infection
Trial locations and contacts
1 site in 1 country.
Burkina Faso1 site
Centre National de Recherche et de Formation sur le Paludisme
Ouagadougou
About this study
Official title: A Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of Low Dose Primaquine for Clearance of Gametocytes in Asymptomatic Individuals Infected With P. Falciparum in Burkina Faso
Primaquine (PQ) is currently the only available drug that can clear mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. However, there are safety concerns about the use of PQ at the currently recommended dose of 0.75mg/kg in individuals who are glucose-6-phosphate dehydrogenase (G6PD) deficient. PQ causes transient but significant haemolysis in G6PD deficient individuals; this side-effect is dose dependent. There are indications that a lower dosing of PQ may effectively reduce gametocyte carriage but the lowest efficacious dose for gametocyte clearance is currently unknown. Recently, the World Health Organization changed their recommendation to a low dose of primaquine, 0.25mg/kg. However, there is no direct evidence on the extent to which (low dose) PQ prevents malaria transmission to mosquitoes and what the lowest efficacious dose is.
In the current study we aim to identify the lowest efficacious dose of PQ in individuals with normal G6PD function. Children with asymptomatic malaria and normal G6PD enzyme function will be randomized to treatment with artemether-lumefantrine alone or in combination with low doses of PQ. All enrolled individuals will receive a full three-day course of AL, and will be randomized to receive a dose of primaquine or placebo with their fifth dose of AL. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For a subset of participants with patent gametocytes, primaquine effect on infectivity to mosquitoes will be assessed by membrane feeding assays
- Conditions
- Malaria, Asymptomatic Malaria, Plasmodium Falciparum
- Being tested
- Artemether-lumefantrine combination, Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine, Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrine combinationDrug
Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquineDrug
Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquineDrug
| Study group | Role | What they receive |
|---|---|---|
| Artemether-Lumefantrine | Active comparator | Artemether-Lumefantrine combination Receives: Drug: Artemether-lumefantrine combination |
| Artemether-Lumefantrine-Primaquine 0.25 | Experimental | Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine Receives: Drug: Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine |
| Artemether-Lumefantrine-Primaquine 0.4 | Experimental | Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine Receives: Drug: Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gametocyte carriage
Gametocyte prevalence at enrolment and on days 2, 3, 7, 10, 14 during follow-up.
The duration of gametocyte carriage in days will be estimated.
Measured: 14 days during follow-up
Secondary outcomes (3)
Transmission to Anopheles gambiae mosquitoes
Mosquito membrane feeding assays will be used to determine the proportion of infected mosquitoes and the oocyst burden in infected mosquitoes.
Measured: day -1, day 3, day 7
Haematological recovery
Haemoglobin concentration will be determined at enrolment and on days 2, 3, 7, 10 and 14 during follow-up. Haemoglobin concentration will be presented as grams per decilitre and as concentration relative to enrolment value.
Measured: 14 days during follow-up
Primaquine and lumefantrine pharmacokinetics
The pharmacokinetic sampling will measure primaquine, lumefantrine and metabolites. Sampling involves 7 venous blood samples during the first 72 hours after treatment and a single later time point at day 7 post initiation of treatment. Drug plasma levels will be related to treatment arm and to the participant's Cytochrome P450 2D6 metabolizer status. CYP2D6 is an enzyme involved in primaquine metabolism.
Measured: 7 days during follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center, Centre national de recherche et de formation sur le paludisme
- Responsible party
- Sponsor
- Investigators
- Alfred Tiono, PhD, MD, Principal investigator, Centre national de recherche et de formation sur le paludisme
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01935882
- Sponsor's protocol ID
- LOPRIM-1
- Acronym
- LOPRIM
- Status last verified
- Sep 2015
- First submitted
- 2 Sep 2013
- Last updated
- 2 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Goncalves BP, Pett H, Tiono AB, Murry D, Sirima SB, Niemi M, Bousema T, Drakeley C, Ter Heine R. Age, Weight, and CYP2D6 Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02590-16. doi: 10.1128/AAC.02590-16. Print 2017 May.
PubMed 28289025Goncalves BP, Tiono AB, Ouedraogo A, Guelbeogo WM, Bradley J, Nebie I, Siaka D, Lanke K, Eziefula AC, Diarra A, Pett H, Bougouma EC, Sirima SB, Drakeley C, Bousema T. Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial. BMC Med. 2016 Mar 8;14:40. doi: 10.1186/s12916-016-0581-y.
PubMed 26952094
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of Low Dose Primaquine for Clearance of Gametocytes in Asymptomatic Individuals Infected With P. Falciparum in Burkina Faso
- ClinicalTrials.gov ID
- NCT01935882
- Acronym / sponsor ID
- LOPRIM / LOPRIM-1
- Conditions
- Malaria, Asymptomatic Malaria, Plasmodium Falciparum
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, Centre national de recherche et de formation sur le paludisme
- Study start
- Sep 2013
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 5 Sep 2013 (estimated)
- 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.
Primaquine (PQ) is currently the only available drug that can clear mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. However, there are safety concerns about the use of PQ at the currently recommended dose of 0.75mg/kg in individuals who are glucose-6-phosphate dehydrogenase (G6PD) deficient. PQ causes transient but significant haemolysis in G6PD deficient individuals; this side-effect is dose dependent. There are indications that a lower dosing of PQ may effectively reduce gametocyte carriage but the lowest efficacious dose for gametocyte clearance is currently unknown. Recently, the World Health Organization changed their recommendation to a low dose of primaquine, 0.25mg/kg. However, there is no direct evidence on the extent to which (low dose) PQ prevents malaria transmission to mosquitoes and what the lowest efficacious dose is.
In the current study we aim to identify the lowest efficacious dose of PQ in individuals with normal G6PD function. Children with asymptomatic malaria and normal G6PD enzyme function will be randomized to treatment with artemether-lumefantrine alone or in combination with low doses of PQ. All enrolled individuals will receive a full three-day course of AL, and will be randomized to receive a dose of primaquine or placebo with their fifth dose of AL. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For a subset of participants with patent gametocytes, primaquine effect on infectivity to mosquitoes will be assessed by membrane feeding assays
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Artemether-Lumefantrine | Active comparator | Drug: Artemether-lumefantrine combinationArtemether-Lumefantrine combination |
| Artemether-Lumefantrine-Primaquine 0.25 | Experimental | Drug: Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquineArtemether-Lumefantrine with a single dose of 0.25mg/kg primaquine |
| Artemether-Lumefantrine-Primaquine 0.4 | Experimental | Drug: Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquineArtemether-Lumefantrine with a single dose of 0.4mg/kg primaquine |
Who may qualify
- Ages
- 2 to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Age > 2 years and <15 years
- Weight over 10kg
- P. falciparum parasitaemia >1,000 parasites and <200,000 parasites/µl
- P. falciparum gametocytes detected by microscopy
- Normal G6PD enzyme function
Key exclusion criteria (11 listed)
- Enrolled in another study
- Fever or history of fever in the last 24 hours
- Evidence of severe illness/ danger signs
- Known allergy to study medications
- Hb < 8g/dL
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 |
|---|---|---|
| Artemether-lumefantrine combination | Drug | Artemether-Lumefantrine |
| Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine | Drug | Artemether-Lumefantrine-Primaquine 0.25 |
| Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine | Drug | Artemether-Lumefantrine-Primaquine 0.4 |
Primary outcome
Gametocyte carriage
Time frame: 14 days during follow-up
Gametocyte prevalence at enrolment and on days 2, 3, 7, 10, 14 during follow-up. The duration of gametocyte carriage in days will be estimated.
3 secondary outcomes
Transmission to Anopheles gambiae mosquitoes
Time frame: day -1, day 3, day 7
Haematological recovery
Time frame: 14 days during follow-up
Primaquine and lumefantrine pharmacokinetics
Time frame: 7 days during follow-up
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 2 Sep 2015.
- Derived from this study: PubMed 28289025Goncalves BP, Pett H, Tiono AB, Murry D, Sirima SB, Niemi M, Bousema T, Drakeley C, Ter Heine R. Age, Weight, and CYP2D6 Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02590-16. doi: 10.1128/AAC.02590-16. Print 2017 May.
- Derived from this study: PubMed 26952094Goncalves BP, Tiono AB, Ouedraogo A, Guelbeogo WM, Bradley J, Nebie I, Siaka D, Lanke K, Eziefula AC, Diarra A, Pett H, Bougouma EC, Sirima SB, Drakeley C, Bousema T. Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial. BMC Med. 2016 Mar 8;14:40. doi: 10.1186/s12916-016-0581-y.
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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.
Alfred Tiono, PhD, MD principal investigator
Centre national de recherche et de formation sur le paludisme
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Artemether-lumefantrine combination, Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine and Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine in people with Malaria and Asymptomatic Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Burkina Faso.
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 6 inclusion and 11 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 2 Sep 2015. 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 Burkina Faso. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Gametocyte carriage (time frame: 14 days during follow-up). 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 NCT01935882, which also lists 2 linked publications.
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 2 Sep 2015.