Plasmodium FalciparumPhase 4NCT02090036
Efficacy and Safety of a Single Low-dose Primaquine for the Clearance of Gametocytes
A Phase 4 study testing Primaquine (For artemether-lumefantrine+primaquine arm) in people with Plasmodium Falciparum, run by Muhimbili University of Health and Allied Sciences at 1 site in Tanzania.
Trial summary
The purpose of this study is to assess efficacy and safety of a single low-dose Primaquine added to standard artemether/lumefantrine treatment for the clearance of Plasmodium falciparum gametocytes among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Plasmodium Falciparum
- What is being tested?
- Primaquine (For artemether-lumefantrine+primaquine arm)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 1 siteTanzania
- Study dates
- Jul 2014to Nov 2014
- 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 and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age of 1 year and above and neither pregnant nor breast feeding.
- Weight over 10 kg.
- Body temperature ≥37.5°C) or history of fever in the last 24 hours.
- P. falciparum mono-infection.
Who cannot join
- Evidence of severe illness malaria or danger signs.
- Known allergy to study medications.
- Hemoglobin <8 g/dl.
- Antimalarials taken within last 2 weeks.
- Blood transfusion within last 90 days and evidence of recent use (within 14 days)of or will be taking other drugs known to cause hemolysis in G6PD deficient subjects.
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Muhimbili University of Health and Allied Sciences
Dar es Salaam, 65001
About this study
Official title: Efficacy and Safety of a Single Low-dose Primaquine Added to Standard Artemether-lumefantrine Treatment for the Clearance of Plasmodium Falciparum Gametocytes.
The purpose of this study is to assess efficacy and safety of a single low-dose Primaquine added to standard artemether/lumefantrine treatment for the clearance of Plasmodium falciparum gametocytes among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status.
Read the detailed description
The current gained successes in malaria control are accredited partly to the availability of efficacious and fast acting artemisinins which are also potent against P. falciparum young gametocytes. Nonetheless, mature gametocytes may persist after treatment, contributing to malaria transmission. Conversely, artemisinin resistance is confirmed in South-east Asia, and it may spread to Africa. New control tools have to be integrated to sustain the gained successes, further reduce transmission and curb the spread of resistance.
Primaquine has strong gametocytocidal effect against mature gametocytes and when added to schizonticidal drugs such as artemether-lumefantrine (AL), it rapidly shorten gametocytes carriage duration, halting disease transmission. Nonetheless, its wide scale use has been hampered by a dose-dependent acute hemolytic anemia it causes in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Conversely, Artemisinins potentiate primaquine activities, thus a low dose of primaquine would be able to clear falciparum gametocytes.
The World Health Organization recommends addition of 0.25 mg/kg single-dose primaquine to Artemisinin based combination therapies in malaria endemic areas including Africa without testing for G6PD status. Nonetheless, the recommendation, relies on historical data from South-East Asia and among African Americans in the United States. Therefore, this study plans to assess safety and efficacy of 0.25 mg/kg single-dose primaquine added to a standard AL treatment against P. falciparum gametocytes clearance among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status..
- Conditions
- Plasmodium Falciparum
- Being tested
- Primaquine (For artemether-lumefantrine+primaquine arm), Placebo (For artemether-lumefantrine arm)
- Keywords
- Efficacy, Safety, Primaquine, Artemether-lumefantrine, Gametocytes
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Primaquine (For artemether-lumefantrine+primaquine arm)Drug
A 0.25 mg/kg single-dose primaquine will be administered concomitantly with the first dose of artemether-lumefantrine in all patients randomized into the artemether-lumefantrine+primaquine arm.
Placebo (For artemether-lumefantrine arm)Drug
Volume of normal saline mixed with coloured fruit juice measured based on weight bands will be given orally concomitantly with first dose of artemether-lumefantrine.
| Study group | Role | What they receive |
|---|---|---|
| artemether-lumefantrine+placebo | Active comparator | In the artemether-lumefantrine arm, the first dose of artemether-lumefantrine will be administered concomitantly with a single-dose placebo. A volume of normal saline will be measured based on weight bands and then will be given to patients. Receives: Drug: Placebo (For artemether-lumefantrine arm) |
| artemether-lumefantrine+primaquine | Experimental | All the recruited patients will be treated with a six doses, 3 days artemether-lumefantrine treatment regimen. However, patients randomized to the artemether-lumefantrine+primaquine arm will be given 0.25 mg/kg single-dose primaquine concomitantly with artemether-lumefantrine first dose. Receives: Drug: Primaquine (For artemether-lumefantrine+primaquine arm) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of days per treatment arm for gametocytes to become undetectable using Quantitative nucleic acid sequence based assay (QT-NASBA).
Measured: 14 days
Secondary outcomes (1)
Mean maximal fall in hemoglobin (g/dl) from enrolment to day 28 of follow-up defined as mean greatest negative difference in hemoglobin per treatment arm.
Measured: 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2014 (estimated)
- Study startJul 2014
- Primary completionOct 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Plasmodium FalciparumStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Muhimbili University of Health and Allied Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet
- Responsible party
- Principal investigator, Richard Mwaiswelo, Muhimbili University of Health and Allied Sciences
- Investigators
- Andreas Martensson, PhD, Study director, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02090036
- Sponsor's protocol ID
- 1.0.2014
- Status last verified
- Dec 2014
- First submitted
- 16 Mar 2014
- Last updated
- 8 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mwaiswelo R, Ngasala B, Jovel I, Xu W, Larsson E, Malmberg M, Gil JP, Premji Z, Mmbando BP, Martensson A. Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2019 May;100(5):1179-1186. doi: 10.4269/ajtmh.18-0729.
PubMed 30860013Mwaiswelo R, Ngasala B, Jovel I, Aydin-Schmidt B, Gosling R, Premji Z, Mmbando B, Bjorkman A, Martensson A. Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial. Malar J. 2016 Aug 26;15(1):435. doi: 10.1186/s12936-016-1430-3.
PubMed 27565897Mwaiswelo R, Ngasala BE, Jovel I, Gosling R, Premji Z, Poirot E, Mmbando BP, Bjorkman A, Martensson A. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Malar J. 2016 Jun 10;15:316. doi: 10.1186/s12936-016-1341-3.
PubMed 27287612
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of a Single Low-dose Primaquine Added to Standard Artemether-lumefantrine Treatment for the Clearance of Plasmodium Falciparum Gametocytes.
- ClinicalTrials.gov ID
- NCT02090036
- Acronym / sponsor ID
- 1.0.2014
- Conditions
- Plasmodium Falciparum
- Keywords
- Efficacy, Safety, Primaquine, Artemether-lumefantrine, Gametocytes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Muhimbili University of Health and Allied SciencesUniversity, hospital or other
- Collaborators
- Karolinska Institutet
- Study start
- Jul 2014
- Primary completion
- Oct 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 18 Mar 2014 (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.
The purpose of this study is to assess efficacy and safety of a single low-dose Primaquine added to standard artemether/lumefantrine treatment for the clearance of Plasmodium falciparum gametocytes among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status.
Detailed description
The current gained successes in malaria control are accredited partly to the availability of efficacious and fast acting artemisinins which are also potent against P. falciparum young gametocytes. Nonetheless, mature gametocytes may persist after treatment, contributing to malaria transmission. Conversely, artemisinin resistance is confirmed in South-east Asia, and it may spread to Africa. New control tools have to be integrated to sustain the gained successes, further reduce transmission and curb the spread of resistance.
Primaquine has strong gametocytocidal effect against mature gametocytes and when added to schizonticidal drugs such as artemether-lumefantrine (AL), it rapidly shorten gametocytes carriage duration, halting disease transmission. Nonetheless, its wide scale use has been hampered by a dose-dependent acute hemolytic anemia it causes in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Conversely, Artemisinins potentiate primaquine activities, thus a low dose of primaquine would be able to clear falciparum gametocytes.
The World Health Organization recommends addition of 0.25 mg/kg single-dose primaquine to Artemisinin based combination therapies in malaria endemic areas including Africa without testing for G6PD status. Nonetheless, the recommendation, relies on historical data from South-East Asia and among African Americans in the United States. Therefore, this study plans to assess safety and efficacy of 0.25 mg/kg single-dose primaquine added to a standard AL treatment against P. falciparum gametocytes clearance among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status..
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| artemether-lumefantrine+placebo | Active comparator | Drug: Placebo (For artemether-lumefantrine arm)In the artemether-lumefantrine arm, the first dose of artemether-lumefantrine will be administered concomitantly with a single-dose placebo. A volume of normal saline will be measured based on weight bands and then will be given to patients. |
| artemether-lumefantrine+primaquine | Experimental | Drug: Primaquine (For artemether-lumefantrine+primaquine arm)All the recruited patients will be treated with a six doses, 3 days artemether-lumefantrine treatment regimen. However, patients randomized to the artemether-lumefantrine+primaquine arm will be given 0.25 mg/kg single-dose primaquine concomitantly with artemether-lumefantrine first dose. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Age of 1 year and above and neither pregnant nor breast feeding.
- Weight over 10 kg.
- Body temperature ≥37.5°C) or history of fever in the last 24 hours.
- P. falciparum mono-infection.
Key exclusion criteria (5 listed)
- Evidence of severe illness malaria or danger signs.
- Known allergy to study medications.
- Hemoglobin <8 g/dl.
- Antimalarials taken within last 2 weeks.
- Blood transfusion within last 90 days and evidence of recent use (within 14 days)of or will be taking other drugs known to cause hemolysis in G6PD deficient subjects.
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 |
|---|---|---|
| Primaquine (For artemether-lumefantrine+primaquine arm)A 0.25 mg/kg single-dose primaquine will be administered concomitantly with the first dose of artemether-lumefantrine in all patients randomized into the artemether-lumefantrine+primaquine arm. | Drug | artemether-lumefantrine+primaquine |
| Placebo (For artemether-lumefantrine arm)Volume of normal saline mixed with coloured fruit juice measured based on weight bands will be given orally concomitantly with first dose of artemether-lumefantrine. | Drug | artemether-lumefantrine+placebo |
Primary outcome
Number of days per treatment arm for gametocytes to become undetectable using Quantitative nucleic acid sequence based assay (QT-NASBA).
Time frame: 14 days
1 secondary outcome
Mean maximal fall in hemoglobin (g/dl) from enrolment to day 28 of follow-up defined as mean greatest negative difference in hemoglobin per treatment arm.
Time frame: 28 days.
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 8 Dec 2014.
- Derived from this study: PubMed 30860013Mwaiswelo R, Ngasala B, Jovel I, Xu W, Larsson E, Malmberg M, Gil JP, Premji Z, Mmbando BP, Martensson A. Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2019 May;100(5):1179-1186. doi: 10.4269/ajtmh.18-0729.
- Derived from this study: PubMed 27565897Mwaiswelo R, Ngasala B, Jovel I, Aydin-Schmidt B, Gosling R, Premji Z, Mmbando B, Bjorkman A, Martensson A. Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial. Malar J. 2016 Aug 26;15(1):435. doi: 10.1186/s12936-016-1430-3.
- Derived from this study: PubMed 27287612Mwaiswelo R, Ngasala BE, Jovel I, Gosling R, Premji Z, Poirot E, Mmbando BP, Bjorkman A, Martensson A. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Malar J. 2016 Jun 10;15:316. doi: 10.1186/s12936-016-1341-3.
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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.
Andreas Martensson, PhD study director
Karolinska Institutet
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 (For artemether-lumefantrine+primaquine arm) in people with Plasmodium Falciparum, run by Muhimbili University of Health and Allied Sciences 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 4 inclusion and 5 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 8 Dec 2014. 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?
Number of days per treatment arm for gametocytes to become undetectable using Quantitative nucleic acid sequence based assay (QT-NASBA). (time frame: 14 days). 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 NCT02090036, which also lists 3 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 8 Dec 2014.