MalariaPhase 3DAPPINCT02259426
Dihydroartemisinin-piperaquine With Low Dose Primaquine to Reduce Malaria Transmission
A Phase 3 study testing Dihydroartemisinin-piperaquine combination (Artekin) and Primaquine in people with Malaria and Asymptomatic Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Kenya.
Trial summary
Primaquine (PQ) is currently the only available drug that can clear the 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 5 to 15 years
- Conditions the study is for
- Malaria, Asymptomatic Malaria, Plasmodium Falciparum
- What is being tested?
- Dihydroartemisinin-piperaquine combination (Artekin) and Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteKenya
- Study dates
- Oct 2014to Dec 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 5 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Microscopically detectable P. falciparum gametocyte carriage
Who cannot join
- Age < 5 years or > 15 years
- Non-falciparum malaria co-infection
- Malaria parasite density ≥ 200,000 parasites/µL
- Clinical symptoms indicating severe malaria
- Axillary temperature ≥ 39°C
- Body Mass Index (BMI) below 16 or above 32 kg/m2
Show all 20Show fewer
- Haemoglobin concentration below 9.5 g/dL
- Anti-malarials taken in last 2 days
- For women: Pregnancy (assessed by clinical examination and urine pregnancy test) or lactation
- Known hypersensitivity to DP or PQ
- History and/or symptoms indicating chronic illness
- Current use of tuberculosis or anti-retroviral medication
- Unable to give written informed consent
- Unwillingness to participate in two membrane feeding assays
- Travel history to Angola, Cameroon, Chad, Central African Republic, Congo, DR Congo, - Equatorial Guinea, Ethiopia, Gabon, Nigeria and Sudan
- Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease
- Taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes - macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole) and cisapride
- Known disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia
- Taking drugs which may be metabolized by cytochrome enzyme CYP2D6 (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine)
- Blood transfusion within last 90 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double Blind Randomized Controlled Trial of Dihydroartemisinin-piperaquine Alone and in Combination With Single Dose Primaquine to Reduce Post-treatment Malaria Transmission.
Primaquine (PQ) is currently the only available drug that can clear the mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. A major caveat to the use of primaquine in mass adminsitrations for the reduction of malaria transmission is that metabolism of the drug in individuals with glucose-6 phosphate dehydrogenase (G6PD) deficiency can lead to transient haemolysis. The haemolytic side effect of PQ is dose-related. Haemolysis is more commonly observed after prolonged PQ treatment but has also been observed in African populations following a single dose of PQ. This haemolysis was self-limiting, largely restricted to G6PD deficient individuals and did not lead to clinical symptoms. Nevertheless, any drug-induced haemolysis is reason for concern and the World Health Organization has therefore reduced the recommended dose of single low dose primaquine from 0.75mg/kg to 0.25mg/kg. This dosage is deemed safe without prior G6PD or Hb screening. However, there is limited direct evidence on the extent to which this dosage of PQ prevents malaria transmission to mosquitoes.
In the current study, the investigators will assess the efficacy of DP in combination with low-dose PQ to prevent onward malaria transmission. The investigators will perform the investigators study in individuals aged 5-15 years who are carry microscopically detectable densities of P. falciparum gametocytes. This age group is chosen because asexual parasite carriage and gametocyte carriage are common in this age group. All enrolled individuals will receive a full three-day course of DP, and will be randomized to receive a dose of primaquine or placebo with their third dose. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For all individuals, the effect of treatment on infectivity to mosquitoes will be assessed by membrane feeding assays at two time points.
- Conditions
- Malaria, Asymptomatic Malaria, Plasmodium Falciparum
- Being tested
- Dihydroartemisinin-piperaquine combination (Artekin), 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.
Dihydroartemisinin-piperaquine combination (Artekin)Drug
PrimaquineDrug
Single-dose 0.25mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Dihydroartemisínin-piperaquine (Artekin) | Active comparator | Dihydroartemisínin-piperaquine combination alone Receives: Drug: Dihydroartemisinin-piperaquine combination (Artekin) |
| Dihydroartemisinin-piperaquine, Primaquine | Experimental | Dihydroartemisinin-piperaquine with single-dose 0.25mg/kg Primaquine Receives: Drug: Dihydroartemisinin-piperaquine combination (Artekin); Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gametocyte prevalence on day 7 after initiation of treatment
Gametocyte prevalence on day 7 after initiation of treatment is measured by molecular methods.
Measured: day 7 of follow-up
Secondary outcomes (4)
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 3 and 7 during follow-up
Haematological recovery
Haemoglobin concentration will be determined at enrolment and on days 2, 3, 7 and 14 during follow-up. Haemoglobin concentration will be presented as grams per decilitre and as concentration relative to enrollment value.
Measured: 14 days during follow-up
Gametocyte sex-ratio
The ratio of male:female gametocytes will be determined at enrolment and on days 2, 3, 7 and 14 during follow-up by qRT-PCR.
Measured: 14 days of follow-up
Gametocyte carriage during follow-up
Gametocyte prevalence at enrolment and on days 2, 3, 7 (primary outcome measure), and 14 during follow-up. The duration of gametocyte carriage in days will be estimated.
Measured: 14 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 posted8 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionSep 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 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, International Centre of Insect Physiology and Ecology (ICIPE)
- Responsible party
- Sponsor
- Investigators
- Teun Bousema, PhD, Principal investigator, Radboud university medical center, London School of hygiene and tropical medicinePatrick Sawa, MD, Principal investigator, ICIPE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02259426
- Sponsor's protocol ID
- DAPPI-1
- Acronym
- DAPPI
- Status last verified
- Jan 2016
- First submitted
- 29 Sep 2014
- Last updated
- 14 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Randomized Controlled Trial of Dihydroartemisinin-piperaquine Alone and in Combination With Single Dose Primaquine to Reduce Post-treatment Malaria Transmission.
- ClinicalTrials.gov ID
- NCT02259426
- Acronym / sponsor ID
- DAPPI / DAPPI-1
- Conditions
- Malaria, Asymptomatic Malaria, Plasmodium Falciparum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- Radboud University Medical Center, International Centre of Insect Physiology and Ecology (ICIPE)
- Study start
- Oct 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 8 Oct 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.
Primaquine (PQ) is currently the only available drug that can clear the mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. A major caveat to the use of primaquine in mass adminsitrations for the reduction of malaria transmission is that metabolism of the drug in individuals with glucose-6 phosphate dehydrogenase (G6PD) deficiency can lead to transient haemolysis. The haemolytic side effect of PQ is dose-related. Haemolysis is more commonly observed after prolonged PQ treatment but has also been observed in African populations following a single dose of PQ. This haemolysis was self-limiting, largely restricted to G6PD deficient individuals and did not lead to clinical symptoms. Nevertheless, any drug-induced haemolysis is reason for concern and the World Health Organization has therefore reduced the recommended dose of single low dose primaquine from 0.75mg/kg to 0.25mg/kg. This dosage is deemed safe without prior G6PD or Hb screening. However, there is limited direct evidence on the extent to which this dosage of PQ prevents malaria transmission to mosquitoes.
In the current study, the investigators will assess the efficacy of DP in combination with low-dose PQ to prevent onward malaria transmission. The investigators will perform the investigators study in individuals aged 5-15 years who are carry microscopically detectable densities of P. falciparum gametocytes. This age group is chosen because asexual parasite carriage and gametocyte carriage are common in this age group. All enrolled individuals will receive a full three-day course of DP, and will be randomized to receive a dose of primaquine or placebo with their third dose. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For all individuals, the effect of treatment on infectivity to mosquitoes will be assessed by membrane feeding assays at two time points.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dihydroartemisínin-piperaquine (Artekin) | Active comparator | Drug: Dihydroartemisinin-piperaquine combination (Artekin)Dihydroartemisínin-piperaquine combination alone |
| Dihydroartemisinin-piperaquine, Primaquine | Experimental | Drug: Dihydroartemisinin-piperaquine combination (Artekin), Drug: PrimaquineDihydroartemisinin-piperaquine with single-dose 0.25mg/kg Primaquine |
Who may qualify
- Ages
- 5 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Microscopically detectable P. falciparum gametocyte carriage
Key exclusion criteria (20 listed)
- Age < 5 years or > 15 years
- Non-falciparum malaria co-infection
- Malaria parasite density ≥ 200,000 parasites/µL
- Clinical symptoms indicating severe malaria
- Axillary temperature ≥ 39°C
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 |
|---|---|---|
| Dihydroartemisinin-piperaquine combination (Artekin) | Drug | Dihydroartemisinin-piperaquine, Primaquine, Dihydroartemisínin-piperaquine (Artekin) |
| PrimaquineSingle-dose 0.25mg/kg | Drug | Dihydroartemisinin-piperaquine, Primaquine |
Primary outcome
Gametocyte prevalence on day 7 after initiation of treatment
Time frame: day 7 of follow-up
Gametocyte prevalence on day 7 after initiation of treatment is measured by molecular methods.
4 secondary outcomes
Transmission to Anopheles gambiae mosquitoes
Time frame: Day 3 and 7 during follow-up
Haematological recovery
Time frame: 14 days during follow-up
Gametocyte sex-ratio
Time frame: 14 days of follow-up
Gametocyte carriage during follow-up
Time frame: 14 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 14 Jan 2016.
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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.
Teun Bousema, PhD principal investigator
Radboud university medical center, London School of hygiene and tropical medicine
Patrick Sawa, MD principal investigator
ICIPE
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 Dihydroartemisinin-piperaquine combination (Artekin) and Primaquine in people with Malaria and Asymptomatic Malaria, run by London School of Hygiene and Tropical Medicine at 1 site in Kenya.
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 1 inclusion and 20 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 14 Jan 2016. 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 Kenya. 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?
Gametocyte prevalence on day 7 after initiation of treatment (time frame: day 7 of follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jan 2016.