Uncomplicated Falciparum MalariaPhase 2/3NCT02461186
Arterolane-PQP Versus DHA-PQP in Uncomplicated Falciparum Malaria in Eastern Myanmar
A Phase 2/3 study testing Arterolane maleate-piperaquine phosphate (Synriam) and Dihydroartemisinin-piperaquine phosphate (Duocotexin) in people with Uncomplicated Falciparum Malaria and Artemisinin-resistant, run by University of Oxford.
Trial summary
Emerging resistance to artemisinins and their partner drugs severely threatens the treatment of falciparum malaria in Myanmar with artemisinin combination therapies. To inform drug policy, it is crucial to evaluate alternative antimalarial treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uncomplicated Falciparum Malaria, Artemisinin-resistant
- What is being tested?
- Arterolane maleate-piperaquine phosphate (Synriam) and Dihydroartemisinin-piperaquine phosphate (Duocotexin)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2015to Jun 2017
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged ≥ 18 year old
- Symptomatic malaria infection, i.e. history of fever or presence of fever >37.5°c (tympanic) within the last 24 hours.
- Microscopic confirmation of asexual stages of P.falciparum (may be mixed with non-falciparum species) with a parasitaemia >10,000 parasites/µL
- Able to take oral medication
- Willingness and ability of patients to comply with the study protocol for the duration of the study
- Written informed consent given to participate in the trial
Who cannot join
- Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age 18 to 45 year old)
- P.falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175,000/µL).
- Signs or symptoms indicative of severe malaria:
- Impaired consciousness
- Severe anaemia (Hct<15%)
- Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venipuncture sites
Show all 23Show fewer
- Respiratory distress
- Severe jaundice
- Have taken a full course DHA-piperaquine, artemether-lumefantrin or other antimalarial treatment in the previous 42 days
- Known hypersensitivity to artemisinins or to piperaquine - defined as history of erythroderma/other severe cutaneous reaction or angioedema
- History of splenectomy
- History of taking medicinal products that are known to prolong the QTc interval, including:
- Antiarrhythmics (e.g. amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol).
- Neuroleptics (e.g. phenothiazines, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide, or thioridazine), antidepressive agents.
- Certain antimicrobial agents, including agents of the following classes:
- macrolides (e.g. erythromycin, clarithromycin),
- fluoroquinolones (e.g. moxifloxacin, sparfloxacin),
- imidazole and triazole antifungal agent,
- pentamidine and saquinavir.
- The non-sedating antihistamines terfenadine, astemizole, mizolastine.
- Other drugs: cisapride, droperidol, domperidone, bepridil, diphemanil, probucol, levomethadyl, methadone, vinca alkaloids, arsenic trioxide.
- History of taking any drug which is known to be metabolised by the cytochrome enzyme CYP2D6 including flecainide, metoprol, imipramine, amitriptyline, clomipramine.
- Family history of sudden unexplained death, or personal or family history of predisposing cardiac conditions for arrhythmia/QT prolongation (including congenital long QT syndrome, arrhythmia, QTc interval greater than 450 milliseconds with either Bazett or Fridericia correction).
About this study
Official title: An Open-label Randomized Trial to Assess the Therapeutic Efficacy of Arterolane-piperaquine Versus Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Falciparum Malaria in Eastern Myanmar, an Area of Emerging Artemisinin-resistant Falciparum Malaria
Emerging resistance to artemisinins and their partner drugs severely threatens the treatment of falciparum malaria in Myanmar with artemisinin combination therapies. To inform drug policy, it is crucial to evaluate alternative antimalarial treatments.
The investigators here propose a randomized clinical trial comparing parasite clearance parameters and efficacy of 3 days arterolane-piperaquine with standard treatment with 3 days dihydroartemisinin (DHA)-piperaquine in adult patients with uncomplicated falciparum malaria in Myanmar stratified for the presence of "K13" mutation in the infecting parasite strains.
Read the detailed description
Primary Objective:
- To assess the parasite clearance half-life of arterolane-piperaquine compared to DHA-piperaquine in patients with artemisinin resistant uncomplicated falciparum malaria, defined by presence of the "K13" mutations in the infecting parasite strain.
Secondary Objectives :
- To assess the therapeutic efficacy of arterolane-piperaquine and DHA-piperaquine for the treatment of uncomplicated falciparum malaria or mixed infection (P.falciparum (PF) + a non-falciparum species) at Day 42, stratified by presence of artemisinin resistance in the infecting parasite strain.
- To assess the frequency of adverse events and serious adverse events of arterolane-piperaquine compared to DHA-piperaquine.
- To assess other efficacy parameters related to parasite clearance and parasite cure rate as well as the gametocyte carriage.
- To obtain pharmacokinetic (PK) and pharmacokinetic/pharmacodynamics (PK/PD) data on arterolane-piperaquine and DHA-piperaquine.
- Being tested
- Arterolane maleate-piperaquine phosphate (Synriam), Dihydroartemisinin-piperaquine phosphate (Duocotexin)
- Keywords
- Arterolane-piperaquine, Dehydroartemisinin-piperaquine, therapeutic efficacy, Uncomplicated falciparum malaria, Artemisinin-resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arterolane maleate-piperaquine phosphate (Synriam)Drug
Dihydroartemisinin-piperaquine phosphate (Duocotexin)Drug
| Study group | Role | What they receive |
|---|---|---|
| Arterolane maleate-piperaquine phosphate (Synriam) | Experimental | Not described Receives: Drug: Arterolane maleate-piperaquine phosphate (Synriam) |
| Dihydroartemisinin-piperaquine phosphate (Duocotexin) | Experimental | Not described Receives: Drug: Dihydroartemisinin-piperaquine phosphate (Duocotexin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peripheral blood parasite half-life
Peripheral blood parasite half-life of the linear portion of the natural logarithm parasite clearance curve in patients with parasitaemia at inclusion >10,000 parasites/µL
Measured: 2 years
Secondary outcomes (1)
42 day PCR corrected adequate clinical and parasitological response (ACPR)
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionJun 2017 (estimated)
- Study completionJun 2017 (estimated)
Why it stopped: Change of the study site due to the current political climate in Myanmar.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uncomplicated Falciparum 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit, Department of Medical Research, Lower Myanmar
- Responsible party
- Sponsor
- Investigators
- Arjen M Dondorp, MD, Principal investigator, Mahidol Oxfrod Tropical Medicine Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02461186
- Sponsor's protocol ID
- BAKMAL1501
- Status last verified
- Nov 2015
- First submitted
- 26 May 2015
- Last updated
- 3 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Randomized Trial to Assess the Therapeutic Efficacy of Arterolane-piperaquine Versus Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Falciparum Malaria in Eastern Myanmar, an Area of Emerging Artemisinin-resistant Falciparum Malaria
- ClinicalTrials.gov ID
- NCT02461186
- Acronym / sponsor ID
- BAKMAL1501
- Keywords
- Arterolane-piperaquine, Dehydroartemisinin-piperaquine, therapeutic efficacy, Uncomplicated falciparum malaria, Artemisinin-resistant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Change of the study site due to the current political climate in Myanmar.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit, Department of Medical Research, Lower Myanmar
- Study start
- Jun 2015
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 3 Jun 2015 (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.
Emerging resistance to artemisinins and their partner drugs severely threatens the treatment of falciparum malaria in Myanmar with artemisinin combination therapies. To inform drug policy, it is crucial to evaluate alternative antimalarial treatments.
The investigators here propose a randomized clinical trial comparing parasite clearance parameters and efficacy of 3 days arterolane-piperaquine with standard treatment with 3 days dihydroartemisinin (DHA)-piperaquine in adult patients with uncomplicated falciparum malaria in Myanmar stratified for the presence of "K13" mutation in the infecting parasite strains.
Detailed description
Primary Objective:
- To assess the parasite clearance half-life of arterolane-piperaquine compared to DHA-piperaquine in patients with artemisinin resistant uncomplicated falciparum malaria, defined by presence of the "K13" mutations in the infecting parasite strain.
Secondary Objectives :
- To assess the therapeutic efficacy of arterolane-piperaquine and DHA-piperaquine for the treatment of uncomplicated falciparum malaria or mixed infection (P.falciparum (PF) + a non-falciparum species) at Day 42, stratified by presence of artemisinin resistance in the infecting parasite strain.
- To assess the frequency of adverse events and serious adverse events of arterolane-piperaquine compared to DHA-piperaquine.
- To assess other efficacy parameters related to parasite clearance and parasite cure rate as well as the gametocyte carriage.
- To obtain pharmacokinetic (PK) and pharmacokinetic/pharmacodynamics (PK/PD) data on arterolane-piperaquine and DHA-piperaquine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arterolane maleate-piperaquine phosphate (Synriam) | Experimental | Drug: Arterolane maleate-piperaquine phosphate (Synriam) |
| Dihydroartemisinin-piperaquine phosphate (Duocotexin) | Experimental | Drug: Dihydroartemisinin-piperaquine phosphate (Duocotexin) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female aged ≥ 18 year old
- Symptomatic malaria infection, i.e. history of fever or presence of fever >37.5°c (tympanic) within the last 24 hours.
- Microscopic confirmation of asexual stages of P.falciparum (may be mixed with non-falciparum species) with a parasitaemia >10,000 parasites/µL
- Able to take oral medication
- Willingness and ability of patients to comply with the study protocol for the duration of the study
Key exclusion criteria (23 listed)
- Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age 18 to 45 year old)
- P.falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175,000/µL).
- Signs or symptoms indicative of severe malaria:
- Have taken a full course DHA-piperaquine, artemether-lumefantrin or other antimalarial treatment in the previous 42 days
- Known hypersensitivity to artemisinins or to piperaquine - defined as history of erythroderma/other severe cutaneous reaction or angioedema
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 |
|---|---|---|
| Arterolane maleate-piperaquine phosphate (Synriam) | Drug | Arterolane maleate-piperaquine phosphate (Synriam) |
| Dihydroartemisinin-piperaquine phosphate (Duocotexin) | Drug | Dihydroartemisinin-piperaquine phosphate (Duocotexin) |
Primary outcome
Peripheral blood parasite half-life
Time frame: 2 years
Peripheral blood parasite half-life of the linear portion of the natural logarithm parasite clearance curve in patients with parasitaemia at inclusion >10,000 parasites/µL
1 secondary outcome
42 day PCR corrected adequate clinical and parasitological response (ACPR)
Time frame: 42 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2015.
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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.
Arjen M Dondorp, MD principal investigator
Mahidol Oxfrod Tropical Medicine Research Unit
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Arterolane maleate-piperaquine phosphate (Synriam) and Dihydroartemisinin-piperaquine phosphate (Duocotexin) in people with Uncomplicated Falciparum Malaria and Artemisinin-resistant, run by University of Oxford.
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 23 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: withdrawn, as of the sponsor's last update on 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Peripheral blood parasite half-life (time frame: 2 years). 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 3 Nov 2015.