Vivax MalariaPhase 3NCT01640574
Comparison Between 7 and 14 Day Primaquine Combined With Dihydroartemisinin-piperaquine or 3 Day Chloroquine Radical Cure of P. Vivax (BPD)
A Phase 3 study testing Dihydroartemisinin-Piperaquine and Chloroquine in people with Vivax Malaria, run by University of Oxford at 1 site in Thailand.
Trial summary
In Southeast Asia, Plasmodium vivax (Pv) infection reaches 50-80% and bears a greater burden of disease than Plasmodium falciparum (Pf). As control over Pf improves, Pv will assume increasingly larger percentages of malaria prevalence. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Vivax Malaria
- What is being tested?
- Dihydroartemisinin-Piperaquine and Chloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 680 participants
- Where
- 1 siteThailand
- Study dates
- Feb 2012to 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 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- ≥ 6 months old
- Microscopic diagnosis of Plasmodium vivax malaria mono-infection
- Participant or parent/guardian is willing and able to give informed consent for participation in the study
- Able (in the Investigators opinion) and willing to comply with all study requirements.
Who cannot join
- Severe malaria
- History of allergy or adverse reaction to artesunate, piperaquine, chloroquine, or primaquine
- Blood transfusion in the past 3 months
- G6PD deficiency by rapid test
- Hematocrit ≤ 25%
- Pregnancy at the time of screening
- Breastfeeding an infant < 6 months old
- Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomised Parallel Open Label Comparison Between 7 and 14 Day Primaquine Combined With 3-day Dihydroartemisinin-piperaquine or 3-day Chloroquine Regimens for Radical Cure of Plasmodium Vivax
In Southeast Asia, Plasmodium vivax (Pv) infection reaches 50-80% and bears a greater burden of disease than Plasmodium falciparum (Pf). As control over Pf improves, Pv will assume increasingly larger percentages of malaria prevalence. The chronicity of Pv, due to the latent liver stage (hypnozoite) not eradicated by chloroquine, causes recurring disability and compounds the economic burden of those with symptomatic disease. The only widely available treatment for hypnozoites is primaquine, which, because of challenges with tolerability, safety in G6PD deficient persons, and compliance, is not commonly prescribed for the treatment of Pv. Currently, chloroquine is used for the treatment of the blood stages of Pv, however, there are concerns about increasing parasite resistance. Alternative treatments, such as artesunate, should be considered in the future of the treatment of blood stage Pv. The use of primaquine in the treatment of hypnozoites (radical cure) should be emphasized so that transmission of Pv can be controlled.
This study aims to determine the optimal primaquine regimen for radical cure of Plasmodium vivax. Chloroquine is currently the standard of treatment for Plasmodium vivax. Chloroquine may have synergistic effects when used with primaquine and due to its long half-life may delay the first relapse of vivax malaria. In contrast, artesunate does not have documented interactions with primaquine and has a very short half-life, thus, presumably will have no impact on first relapse. Combining primaquine with these two anti-malarials may lead to an alternative regimen for Pv infection and changing the primaquine dosing regimen may lead to a more practical and efficacious therapy.
- Conditions
- Vivax Malaria
- Being tested
- Dihydroartemisinin-Piperaquine, Chloroquine
- Keywords
- Vivax, Chloroquine, Primaquine, Dihydroartemisinin-Piperaquine
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dihydroartemisinin-PiperaquineDrug
Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days
Dihydroartemisinin-PiperaquineDrug
Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days
ChloroquineDrug
Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days
ChloroquineDrug
- Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days
| Study group | Role | What they receive |
|---|---|---|
| DHA-P 7 days | Experimental | Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days Receives: Drug: Dihydroartemisinin-Piperaquine |
| DHA-P 14 days | Experimental | Dihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days Receives: Drug: Dihydroartemisinin-Piperaquine |
| Chloroquine 7 days | Active comparator | Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days Receives: Drug: Chloroquine |
| Chloroquine 14 days | Active comparator | Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days Receives: Drug: Chloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of P. vivax
Recurrence with Plasmodium vivax malaria within 52 weeks of first treatment dose
Measured: 52 weeks
Secondary outcomes (3)
Adverse Events
Number of adverse events within 28 days of study medication
Measured: 28 days
Recurrence of P. vivax
Recurrence with Plasmodium vivax malaria within 6 months of first treatment dose
Measured: 6 months
Drug concentrations
Chloroquine, piperaquine and primaquine drug levels
Measured: 63 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2012 (estimated)
- Study startFeb 2012
- Primary completionJul 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Vivax MalariaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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
- 680 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francois Nosten, MD, Principal investigator, University of OxfordCindy Chu, MD, Principal investigator, Shoklo Malaria Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01640574
- Sponsor's protocol ID
- SMRU1102
- Status last verified
- Apr 2016
- First submitted
- 11 Jul 2012
- Last updated
- 28 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Stadler E, Cromer D, Mehra S, Adekunle AI, Flegg JA, Anstey NM, Watson JA, Chu CS, Mueller I, Robinson LJ, Schlub TE, Davenport MP, Khoury DS. Population heterogeneity in Plasmodium vivax relapse risk. PLoS Negl Trop Dis. 2022 Dec 19;16(12):e0010990. doi: 10.1371/journal.pntd.0010990. eCollection 2022 Dec.
PubMed 36534705Chu CS, Watson JA, Phyo AP, Win HH, Yotyingaphiram W, Thinraow S, Soe NL, Aung AA, Wilaisrisak P, Kraft K, Imwong M, Hanpithakpong W, Blessborn D, Tarning J, Proux S, Ling C, Nosten FH, White NJ. Determinants of Primaquine and Carboxyprimaquine Exposures in Children and Adults with Plasmodium vivax Malaria. Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0130221. doi: 10.1128/AAC.01302-21. Epub 2021 Aug 16.
PubMed 34398667Chu CS, Phyo AP, Turner C, Win HH, Poe NP, Yotyingaphiram W, Thinraow S, Wilairisak P, Raksapraidee R, Carrara VI, Paw MK, Wiladphaingern J, Proux S, Bancone G, Sriprawat K, Lee SJ, Jeeyapant A, Watson J, Tarning J, Imwong M, Nosten F, White NJ. Chloroquine Versus Dihydroartemisinin-Piperaquine With Standard High-dose Primaquine Given Either for 7 Days or 14 Days in Plasmodium vivax Malaria. Clin Infect Dis. 2019 Apr 8;68(8):1311-1319. doi: 10.1093/cid/ciy735.
PubMed 30952158Chu CS, Bancone G, Moore KA, Win HH, Thitipanawan N, Po C, Chowwiwat N, Raksapraidee R, Wilairisak P, Phyo AP, Keereecharoen L, Proux S, Charunwatthana P, Nosten F, White NJ. Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens. PLoS Med. 2017 Feb 7;14(2):e1002224. doi: 10.1371/journal.pmed.1002224. eCollection 2017 Feb.
PubMed 28170391
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Parallel Open Label Comparison Between 7 and 14 Day Primaquine Combined With 3-day Dihydroartemisinin-piperaquine or 3-day Chloroquine Regimens for Radical Cure of Plasmodium Vivax
- ClinicalTrials.gov ID
- NCT01640574
- Acronym / sponsor ID
- SMRU1102
- Conditions
- Vivax Malaria
- Keywords
- Vivax, Chloroquine, Primaquine, Dihydroartemisinin-Piperaquine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 680 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 13 Jul 2012 (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 Southeast Asia, Plasmodium vivax (Pv) infection reaches 50-80% and bears a greater burden of disease than Plasmodium falciparum (Pf). As control over Pf improves, Pv will assume increasingly larger percentages of malaria prevalence. The chronicity of Pv, due to the latent liver stage (hypnozoite) not eradicated by chloroquine, causes recurring disability and compounds the economic burden of those with symptomatic disease. The only widely available treatment for hypnozoites is primaquine, which, because of challenges with tolerability, safety in G6PD deficient persons, and compliance, is not commonly prescribed for the treatment of Pv. Currently, chloroquine is used for the treatment of the blood stages of Pv, however, there are concerns about increasing parasite resistance. Alternative treatments, such as artesunate, should be considered in the future of the treatment of blood stage Pv. The use of primaquine in the treatment of hypnozoites (radical cure) should be emphasized so that transmission of Pv can be controlled.
This study aims to determine the optimal primaquine regimen for radical cure of Plasmodium vivax. Chloroquine is currently the standard of treatment for Plasmodium vivax. Chloroquine may have synergistic effects when used with primaquine and due to its long half-life may delay the first relapse of vivax malaria. In contrast, artesunate does not have documented interactions with primaquine and has a very short half-life, thus, presumably will have no impact on first relapse. Combining primaquine with these two anti-malarials may lead to an alternative regimen for Pv infection and changing the primaquine dosing regimen may lead to a more practical and efficacious therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| DHA-P 7 days | Experimental | Drug: Dihydroartemisinin-PiperaquineDihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days |
| DHA-P 14 days | Experimental | Drug: Dihydroartemisinin-PiperaquineDihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days |
| Chloroquine 7 days | Active comparator | Drug: ChloroquineChloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days |
| Chloroquine 14 days | Active comparator | Drug: ChloroquineChloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- ≥ 6 months old
- Microscopic diagnosis of Plasmodium vivax malaria mono-infection
- Participant or parent/guardian is willing and able to give informed consent for participation in the study
- Able (in the Investigators opinion) and willing to comply with all study requirements.
Key exclusion criteria (8 listed)
- Severe malaria
- History of allergy or adverse reaction to artesunate, piperaquine, chloroquine, or primaquine
- Blood transfusion in the past 3 months
- G6PD deficiency by rapid test
- Hematocrit ≤ 25%
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-PiperaquineDihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days and Primaquine 1 mg/kg once daily for 7 days | Drug | DHA-P 7 days |
| Dihydroartemisinin-PiperaquineDihydroartemisinin-piperaquine + Primaquine: DHA-P 7mg/kg/day dihydroartemisinin and 55mg/kg/day piperaquine daily for 3 days Primaquine 0.5 mg/kg daily for 14 days | Drug | DHA-P 14 days |
| ChloroquineChloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 1 mg/kg once daily for 7 days | Drug | Chloroquine 7 days |
| Chloroquineo Chloroquine + Primaquine: Chloroquine 10, 10, 5 and Primaquine 0.5 mg/kg daily for 14 days | Drug | Chloroquine 14 days |
Primary outcome
Recurrence of P. vivax
Time frame: 52 weeks
Recurrence with Plasmodium vivax malaria within 52 weeks of first treatment dose
3 secondary outcomes
Adverse Events
Time frame: 28 days
Recurrence of P. vivax
Time frame: 6 months
Drug concentrations
Time frame: 63 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 28 Apr 2016.
- Derived from this study: PubMed 36534705Stadler E, Cromer D, Mehra S, Adekunle AI, Flegg JA, Anstey NM, Watson JA, Chu CS, Mueller I, Robinson LJ, Schlub TE, Davenport MP, Khoury DS. Population heterogeneity in Plasmodium vivax relapse risk. PLoS Negl Trop Dis. 2022 Dec 19;16(12):e0010990. doi: 10.1371/journal.pntd.0010990. eCollection 2022 Dec.
- Derived from this study: PubMed 34398667Chu CS, Watson JA, Phyo AP, Win HH, Yotyingaphiram W, Thinraow S, Soe NL, Aung AA, Wilaisrisak P, Kraft K, Imwong M, Hanpithakpong W, Blessborn D, Tarning J, Proux S, Ling C, Nosten FH, White NJ. Determinants of Primaquine and Carboxyprimaquine Exposures in Children and Adults with Plasmodium vivax Malaria. Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0130221. doi: 10.1128/AAC.01302-21. Epub 2021 Aug 16.
- Derived from this study: PubMed 30952158Chu CS, Phyo AP, Turner C, Win HH, Poe NP, Yotyingaphiram W, Thinraow S, Wilairisak P, Raksapraidee R, Carrara VI, Paw MK, Wiladphaingern J, Proux S, Bancone G, Sriprawat K, Lee SJ, Jeeyapant A, Watson J, Tarning J, Imwong M, Nosten F, White NJ. Chloroquine Versus Dihydroartemisinin-Piperaquine With Standard High-dose Primaquine Given Either for 7 Days or 14 Days in Plasmodium vivax Malaria. Clin Infect Dis. 2019 Apr 8;68(8):1311-1319. doi: 10.1093/cid/ciy735.
- Derived from this study: PubMed 28170391Chu CS, Bancone G, Moore KA, Win HH, Thitipanawan N, Po C, Chowwiwat N, Raksapraidee R, Wilairisak P, Phyo AP, Keereecharoen L, Proux S, Charunwatthana P, Nosten F, White NJ. Haemolysis in G6PD Heterozygous Females Treated with Primaquine for Plasmodium vivax Malaria: A Nested Cohort in a Trial of Radical Curative Regimens. PLoS Med. 2017 Feb 7;14(2):e1002224. doi: 10.1371/journal.pmed.1002224. eCollection 2017 Feb.
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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.
Francois Nosten, MD principal investigator
University of Oxford
Cindy Chu, MD principal investigator
Shoklo Malaria Research Unit
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 and Chloroquine in people with Vivax Malaria, run by University of Oxford at 1 site in Thailand.
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 8 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 28 Apr 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 Thailand. 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?
Recurrence of P. vivax (time frame: 52 weeks). 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 NCT01640574, which also lists 4 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 28 Apr 2016.