MalariaPhase 3PRINOGAMNCT01838902
Primaquine's Gametocytocidal Efficacy in Malaria Asymptomatic Carriers
A Phase 3 study testing DHA-PPQ, PQ (0.75) and PQ (0.4) in people with Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
Trial summary
In this study, the investigators are interested to know if lower doses of Primaquine together with dihydroartemisinin-piperaquine can produce a similar effect of clearing both sexual and asexual parasites in asymptomatic carriers compared to the recommended dose of primaquine but with a decreased risk of haemolysis. Read more about this study
- Who is it for?
- Ages 12 months and olderHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- DHA-PPQ, PQ (0.75) and PQ (0.4)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 467 participants
- Where
- 1 siteThe Gambia
- Study dates
- Aug 2013to Oct 2015
- Phase
- Phase 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 12 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Age ≥1 year
- Weight >10 Kg
- P. falciparum mono-infection, density of at least 20 parasites/μL
- Axillary temperature < 37.5ºC
- Resident in the study area and willingness to reside for the duration of the study
- Written informed consent (plus an assent in children >12years of age)
Who cannot join
- G6PD Deficiency Haemoglobin <8g/dl
- Known allergy to any of the study medications
- Known Pregnancy or breastfeeding
- Clear/documented history of anti-malarial treatment 2 weeks before contact with study team
- History of blood transfusion in the previous 3 months
- Any chronic or acute conditions that might interfere with the study as judged by the research clinician
- History of sickle cell anaemia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Primaquine's Gametocytocidal Efficacy in Malaria Asymptomatic Carriers Treated With Dihydroartemisinin-piperaquine in The Gambia
In this study, the investigators are interested to know if lower doses of Primaquine together with dihydroartemisinin-piperaquine can produce a similar effect of clearing both sexual and asexual parasites in asymptomatic carriers compared to the recommended dose of primaquine but with a decreased risk of haemolysis.
Children (> 1 year) and adults with normal Glucose-6-phosphate dehydrogenase enzyme levels but with asexual Plasmodium falciparum parasites on the day of screening will be invited to take part in this study.
Read the detailed description
To date, primaquine (PQ), an 8-aminoquinoline, is the only currently registered product able to clear P. falciparum mature gametocytes. However, its use has been and is still limited by its haematological toxicity (haemolytic anaemia), particularly but not exclusively in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd), in whom haemolysis can occur after a single PQ dose. Such an effect is dose-dependent. Considering that the current recommended dose was established several decades ago on a small number of experimentally challenged volunteers, it may be possible to obtain the same effect with a lower dose and hence decrease the risk of haemolysis. The proposed study is a four-arm, open label, randomized, controlled trial. G6PD-normal asymptomatic P. falciparum infected individuals identified through population screening will be randomized to receive either a complete course of dihydroartemisinin-piperaquine (DHA-PPQ) alone (control arm) or a complete course of DHA-PPQ plus a single dose of PQ at 3 differing dose strengths (intervention arms), i.e. 0.75mg/kg, 0.4mg base/kg and 0.2mg base/kg.
The study is planned to enroll 1,200 individuals with an asymptomatic malaria infection during the rainy /transmission season (June - December) from villages around the MRC's field stations at Walikunda and Basse in The Gambia. Asymptomatic parasite carriers identified by qualitative (RDT) and quantitative (parasites counts >20/µl by slide microscopy) methods during population screening exercises at the villages will be invited for a written informed consent and further screening to confirm eligibility, including tests for qualitative G6PD enzyme function (fluorescence spot test) and haemoglobin. If eligible, they will be assigned to one of four study arms using a block randomization scheme in a 1:1:1:1 ratio ensuring a balance in enrollment between the four groups. Enrolled participants will receive ACT treatment on days 0, 1 and 2. On day 2, participants allocated to the PQ arms will receive a dose of primaquine based on determined body weight.
Each participant involvement consists of a maximum of 11 visits over a 42 day period after initiation of treatment. The primary end point is the prevalence of P. falciparum gametocyte carriers at day 7, as determined by QT-NASBA.
- Conditions
- Malaria
- Being tested
- DHA-PPQ, PQ (0.75), PQ (0.4), PQ (0.2)
- Keywords
- Malaria, Falciparum, Direct membrane feeding, QT-NASBA, Asexual parasite, Asymptomatic carrier, Gametocytocidal, Gametocyte, Transmission blocking, Sexual stage, Primaquine, Dihydroartemisinin, Piperaquine, Gambia, Africa
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DHA-PPQDrug
Also called Eurartesim
Participants will receive a 3 day course of DHA-PPQ
PQ (0.75)Drug
Also called Primaquine
Participants will receive a single dose of PQ at 0.75mg base/kg body weight
PQ (0.4)Drug
Also called Primaquine
Participants will receive a single dose of PQ at 0.4mg base/kg body weight
PQ (0.2)Drug
Also called Primaquine
Participants will receive a single dose of PQ at 0.2mg base/kg body weight
| Study group | Role | What they receive |
|---|---|---|
| Eurartesim (control) | Other | All participants will receive a complete course of DHA-PPQ (Eurartesim) Receives: Drug: DHA-PPQ |
| Primaquine 0.75mg base/kg | Experimental | Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.75mg/kg body weight Receives: Drug: DHA-PPQ; Drug: PQ (0.75) |
| Primaquine 0.4mg base /kg | Experimental | Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.4mg base/kg Body weight Receives: Drug: DHA-PPQ; Drug: PQ (0.4) |
| Primaquine 0.2mg base/kg | Experimental | Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.2mg base/kg body weight Receives: Drug: DHA-PPQ; Drug: PQ (0.2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of P. falciparum gametocyte carriers (QT-NASBA)
Proportion of study participants in each arm with P. falciparum gametocyte carriers as determined by quantitative nucleic acid sequence based amplification assay (QT-NASBA)
Measured: Day 7
Secondary outcomes (6)
Prevalence of P.Falciparum gametocytes carriers
Prevalence of P. falciparum gametocyte carriers on days 3, 10, 14, 28 and 42, as determined by QT-NASBA
Measured: Days 3, 10, 14, 28 and 42
Proportion of individuals infectious to mosquitoes (DMFA)
% of individuals whose day 7 blood samples when fed to mosquitoes by direct membrane feeding assay
Measured: Day 7
Haemoglobin change
Mean (±SD) difference in haemoglobin measured between baseline (day 0) and each follow up visit day by study arm
Measured: Day 0 and days 3, 7, 10, 14, 21, 28, 35 and 42
Prevalence of infection (asexual stages)
Proportion of participants carrying asexual forms of P. Falciparum on day 3
Measured: Day 3
Proportion of participants with recurrent infection (PCR adjusted and unadjusted)
% of participants previously negative for parasites with detectable parasite (by microscopy and PCR) in samples after day 7
Measured: Day 7 to Day 42
Occurrence of adverse events (AEs) and serious adverse events (SAEs)
Occurrence of adverse events (AEs) and serious adverse events (SAEs) during follow up
Measured: Day 3 to Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2013 (estimated)
- Study startAug 2013
- Primary completionFeb 2015
- Study completionOct 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 467 participants (actual)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Umberto D'Alessandro, MD, PhD, Principal investigator, MRC Unit, Fajara The Gambia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01838902
- Sponsor's protocol ID
- SCC 1321
- Acronym
- PRINOGAM
- Status last verified
- Mar 2018
- First submitted
- 12 Apr 2013
- Last updated
- 22 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Okebe J, Bousema T, Affara M, Di Tanna GL, Dabira E, Gaye A, Sanya-Isijola F, Badji H, Correa S, Nwakanma D, Van Geertruyden JP, Drakeley C, D'Alessandro U. The Gametocytocidal Efficacy of Different Single Doses of Primaquine with Dihydroartemisinin-piperaquine in Asymptomatic Parasite Carriers in The Gambia: A Randomized Controlled Trial. EBioMedicine. 2016 Nov;13:348-355. doi: 10.1016/j.ebiom.2016.10.032. Epub 2016 Oct 23.
PubMed 27825738Okebe J, Bousema T, Affara M, DiTanna G, Eziefula AC, Jawara M, Nwakanma D, Amambua-Ngwa A, Van Geertruyden JP, Drakeley C, D'Alessandro U. The gametocytocidal efficacy of primaquine in malaria asymptomatic carriers treated with dihydroartemisinin-piperaquine in The Gambia (PRINOGAM): study protocol for a randomised controlled trial. Trials. 2015 Mar 1;16:70. doi: 10.1186/s13063-015-0597-1.
PubMed 25887344
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Primaquine's Gametocytocidal Efficacy in Malaria Asymptomatic Carriers Treated With Dihydroartemisinin-piperaquine in The Gambia
- ClinicalTrials.gov ID
- NCT01838902
- Acronym / sponsor ID
- PRINOGAM / SCC 1321
- Conditions
- Malaria
- Keywords
- Malaria, Falciparum, Direct membrane feeding, QT-NASBA, Asexual parasite, Asymptomatic carrier, Gametocytocidal, Gametocyte, Transmission blocking
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 467 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 24 Apr 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.
In this study, the investigators are interested to know if lower doses of Primaquine together with dihydroartemisinin-piperaquine can produce a similar effect of clearing both sexual and asexual parasites in asymptomatic carriers compared to the recommended dose of primaquine but with a decreased risk of haemolysis.
Children (> 1 year) and adults with normal Glucose-6-phosphate dehydrogenase enzyme levels but with asexual Plasmodium falciparum parasites on the day of screening will be invited to take part in this study.
Detailed description
To date, primaquine (PQ), an 8-aminoquinoline, is the only currently registered product able to clear P. falciparum mature gametocytes. However, its use has been and is still limited by its haematological toxicity (haemolytic anaemia), particularly but not exclusively in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd), in whom haemolysis can occur after a single PQ dose. Such an effect is dose-dependent. Considering that the current recommended dose was established several decades ago on a small number of experimentally challenged volunteers, it may be possible to obtain the same effect with a lower dose and hence decrease the risk of haemolysis. The proposed study is a four-arm, open label, randomized, controlled trial. G6PD-normal asymptomatic P. falciparum infected individuals identified through population screening will be randomized to receive either a complete course of dihydroartemisinin-piperaquine (DHA-PPQ) alone (control arm) or a complete course of DHA-PPQ plus a single dose of PQ at 3 differing dose strengths (intervention arms), i.e. 0.75mg/kg, 0.4mg base/kg and 0.2mg base/kg.
The study is planned to enroll 1,200 individuals with an asymptomatic malaria infection during the rainy /transmission season (June - December) from villages around the MRC's field stations at Walikunda and Basse in The Gambia. Asymptomatic parasite carriers identified by qualitative (RDT) and quantitative (parasites counts >20/µl by slide microscopy) methods during population screening exercises at the villages will be invited for a written informed consent and further screening to confirm eligibility, including tests for qualitative G6PD enzyme function (fluorescence spot test) and haemoglobin. If eligible, they will be assigned to one of four study arms using a block randomization scheme in a 1:1:1:1 ratio ensuring a balance in enrollment between the four groups. Enrolled participants will receive ACT treatment on days 0, 1 and 2. On day 2, participants allocated to the PQ arms will receive a dose of primaquine based on determined body weight.
Each participant involvement consists of a maximum of 11 visits over a 42 day period after initiation of treatment. The primary end point is the prevalence of P. falciparum gametocyte carriers at day 7, as determined by QT-NASBA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Eurartesim (control) | Other | Drug: DHA-PPQAll participants will receive a complete course of DHA-PPQ (Eurartesim) |
| Primaquine 0.75mg base/kg | Experimental | Drug: DHA-PPQ, Drug: PQ (0.75)Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.75mg/kg body weight |
| Primaquine 0.4mg base /kg | Experimental | Drug: DHA-PPQ, Drug: PQ (0.4)Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.4mg base/kg Body weight |
| Primaquine 0.2mg base/kg | Experimental | Drug: DHA-PPQ, Drug: PQ (0.2)Participants will be randomized to receive a complete course of DHA-PPQ plus a single dose of PQ at 0.2mg base/kg body weight |
Who may qualify
- Ages
- 12 months and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥1 year
- Weight >10 Kg
- P. falciparum mono-infection, density of at least 20 parasites/μL
- Axillary temperature < 37.5ºC
- Resident in the study area and willingness to reside for the duration of the study
Key exclusion criteria (7 listed)
- G6PD Deficiency Haemoglobin <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 |
|---|---|---|
| DHA-PPQAlso: EurartesimParticipants will receive a 3 day course of DHA-PPQ | Drug | Eurartesim (control), Primaquine 0.2mg base/kg, Primaquine 0.4mg base /kg, Primaquine 0.75mg base/kg |
| PQ (0.75)Also: PrimaquineParticipants will receive a single dose of PQ at 0.75mg base/kg body weight | Drug | Primaquine 0.75mg base/kg |
| PQ (0.4)Also: PrimaquineParticipants will receive a single dose of PQ at 0.4mg base/kg body weight | Drug | Primaquine 0.4mg base /kg |
| PQ (0.2)Also: PrimaquineParticipants will receive a single dose of PQ at 0.2mg base/kg body weight | Drug | Primaquine 0.2mg base/kg |
Primary outcome
Prevalence of P. falciparum gametocyte carriers (QT-NASBA)
Time frame: Day 7
Proportion of study participants in each arm with P. falciparum gametocyte carriers as determined by quantitative nucleic acid sequence based amplification assay (QT-NASBA)
6 secondary outcomes
Prevalence of P.Falciparum gametocytes carriers
Time frame: Days 3, 10, 14, 28 and 42
Proportion of individuals infectious to mosquitoes (DMFA)
Time frame: Day 7
Haemoglobin change
Time frame: Day 0 and days 3, 7, 10, 14, 21, 28, 35 and 42
Prevalence of infection (asexual stages)
Time frame: Day 3
Proportion of participants with recurrent infection (PCR adjusted and unadjusted)
Time frame: Day 7 to Day 42
Occurrence of adverse events (AEs) and serious adverse events (SAEs)
Time frame: Day 3 to Day 42
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 22 Mar 2018.
- Derived from this study: PubMed 27825738Okebe J, Bousema T, Affara M, Di Tanna GL, Dabira E, Gaye A, Sanya-Isijola F, Badji H, Correa S, Nwakanma D, Van Geertruyden JP, Drakeley C, D'Alessandro U. The Gametocytocidal Efficacy of Different Single Doses of Primaquine with Dihydroartemisinin-piperaquine in Asymptomatic Parasite Carriers in The Gambia: A Randomized Controlled Trial. EBioMedicine. 2016 Nov;13:348-355. doi: 10.1016/j.ebiom.2016.10.032. Epub 2016 Oct 23.
- Derived from this study: PubMed 25887344Okebe J, Bousema T, Affara M, DiTanna G, Eziefula AC, Jawara M, Nwakanma D, Amambua-Ngwa A, Van Geertruyden JP, Drakeley C, D'Alessandro U. The gametocytocidal efficacy of primaquine in malaria asymptomatic carriers treated with dihydroartemisinin-piperaquine in The Gambia (PRINOGAM): study protocol for a randomised controlled trial. Trials. 2015 Mar 1;16:70. doi: 10.1186/s13063-015-0597-1.
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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.
Umberto D'Alessandro, MD, PhD principal investigator
MRC Unit, Fajara The Gambia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing DHA-PPQ, PQ (0.75) and PQ (0.4) in people with Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
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 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 22 Mar 2018. 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 The Gambia. 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 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?
Prevalence of P. falciparum gametocyte carriers (QT-NASBA) (time frame: Day 7). 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 NCT01838902, 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 22 Mar 2018.