Vivax MalariaPhase 2BlueALNCT02696928
Methylene Blue Against Vivax Malaria in Ethiopia
A Phase 2 study testing Artemeter-Lumefantrine and MB (combination therapy), Artemeter-Lumefantrine (combination therapy) and Artemeter-Lumefantrine and Primaquine (combination therapy) in people with Vivax Malaria, run by Heidelberg University.
Trial summary
Feasibility of methylene blue-based combination therapy in the radical treatment of adult patients with Plasmodium vivax malaria in Ethiopia: a randomised controlled pilot trial Study rationale: Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vivax Malaria
- What is being tested?
- Artemeter-Lumefantrine and MB (combination therapy), Artemeter-Lumefantrine (combination therapy) and Artemeter-Lumefantrine and Primaquine (combination therapy)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Apr 2016to Jan 2018
- Phase
- Phase 2
- 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
- Age ≥18 years
- Uncomplicated P. vivax monoinfection (asexual parasite count >250/µl)
- Axillary temperature ≥ 37.5°C or history of fever during last 48 hours
- Ability to tolerate oral drug therapy
- Written informed consent of patient
- Permanent residence in the study area
Who cannot join
- Therapy with an antimalarial (e.g. CQ, amodiaquine, pyrimethamine-sulfadoxine, quinine, any ACT) or an antibiotic which is effective against malaria parasites (e.g. doxycyclin, clindamycin, CoTrim) during last three weeks
- Mixed malaria infection
- Clinical danger signals (e.g. unable to stand or to sit, unable to drink, repeated vomiting, convulsions) or signs and symptoms of severe malaria (according to WHO definition)
- Known other serious illnesses (e.g. cardiac, renal, hepatic, pulmonary disease, severe malnutrition, severe infectious diseases)
- G6PD deficiency (<60% activity, WHO classification 1-3)
- Patients with known allergy to one or more of the study drugs
- Hemoglobin value <7 g/dL
- Pregnancy or breastfeeding
About this study
Official title: Feasibility of Methylene Blue-based Combination Therapy in the Radical Treatment of Adult Patients With Plasmodium Vivax Malaria in Ethiopia: a Randomised Controlled Pilot Trial
Feasibility of methylene blue-based combination therapy in the radical treatment of adult patients with Plasmodium vivax malaria in Ethiopia: a randomised controlled pilot trial
Study rationale:
Read more
Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. Primaquine (PQ) is the only registered drug for radical cure of Plasmodium vivax malaria. Prolonged PQ-based combination therapy carries safety concerns and resistance to chloroquine (CQ) and PQ is emerging. Methylene blue (MB) has recently been shown to be safe and effective in the treatment of Plasmodium falciparum malaria in West Africa. As there is evidence for MB probably being effective against the hypnozoites of Plasmodium vivax, MB-based drug regimens could be an alternative to PQ-based combination therapy in Plasmodium vivax malaria.
Study objectives:
The main objective of this trial is to study the feasibility of MB-based combination therapy in patients with uncomplicated P. vivax malaria in an endemic area of Ethiopia.
Read the detailed description
The specific aims are (1) to test the feasibility and costs of methods and procedures for later use of MB-based combination therapy on a large scale, (2) to assess the safety of MB-based combination therapy, (3) to estimate the efficacy of MB-based combination therapy against malaria relapse, (4) to study the community acceptance of MB-based combination therapy, and (5) to strengthen the local capacity for malaria research and control in Jimma/Ethiopia.
Study design:
The study is designed as a pilot trial in adult patients with uncomplicated P. vivax malaria in Jimma, Ethiopia. Patients will be randomised to three treatment groups:
- Arthemeter/Lumefantrine (AL)
- AL-PQ, and
- AL-MB. Follow-up will be over a period of 6 months.
Study population:
Adult patients with uncomplicated P. vivax malaria (age ≥18 years) in Jimma/Ethiopia (G6PD deficient subjects are excluded) will become enrolled in the outpatient departments of the study centres. The sample size will be 33 per study arm, a total of 99 patients.
Study treatments:
- AL standard treatments twice daily (total of 80 mg/dose A plus 480 mg/dose L) over first three study days
- PQ 15 mg once daily for 14 days
- MB 780 mg once daily for 14 days Treatments will be 100% directly observed.
Study outcomes:
Outcome parameters will be on feasibility and costs (e.g. recruitment rates, retention rates, costs per patient), on safety parameters (e.g. haemoglobin development during follow-up, incidence of adverse events), on efficacy parameters (e.g. incidence of P. vivax relapse during follow-up, malaria recurrence-free efficacy until day 180), and on community acceptance (e.g. perceptions on blue urine) during follow-up.
- Conditions
- Vivax Malaria
- Being tested
- Artemeter-Lumefantrine and MB (combination therapy), Artemeter-Lumefantrine (combination therapy), Artemeter-Lumefantrine and Primaquine (combination therapy)
- Medical subject headings
- Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemeter-Lumefantrine and MB (combination therapy)Drug
Also called 3,7-bis(Dimethylamino)-phenothiazin-5-ium chloride, CID 6099
AL first 3 days MB next 14 days
Artemeter-Lumefantrine (combination therapy)Drug
Also called AL
AL first 3 days
Artemeter-Lumefantrine and Primaquine (combination therapy)Drug
Also called AL and PQ
AL first 3 days PQ next 14 days
| Study group | Role | What they receive |
|---|---|---|
| Artemeter-Lumefantrine (combination therapy) | Other | 33 patients
(standard of care) Receives: Drug: Artemeter-Lumefantrine (combination therapy) |
| Artemeter-Lumefantrine and Primaquine (combination therapy) | Active comparator | 33 patients Receives: Drug: Artemeter-Lumefantrine and Primaquine (combination therapy) |
| Artemeter-Lumefantrine and MB (combination therapy) | Experimental | 33 patients Receives: Drug: Artemeter-Lumefantrine and MB (combination therapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study feasibility
Patient recruitment rates
Measured: 180 days
Secondary outcomes (3)
Incidence of P. vivax
Passive and active surveillance
Measured: 180 days
Adverse events (AE) during total follow-up period
Passive and active surveillance
Measured: 180 days
Study costs
Costs per patient
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2016 (estimated)
- Study startApr 2016
- Primary completionOct 2017 (estimated)
- Study completionJan 2018 (estimated)
Why it stopped: Lack of ethical approval in Ethiopia
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vivax 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, Jimma University
- Responsible party
- Principal investigator, Olaf Mueller, Heidelberg University
- Investigators
- Olaf Müller, Prof. Dr., Principal investigator, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02696928
- Sponsor's protocol ID
- UniHD007
- Acronym
- BlueAL
- Status last verified
- Mar 2020
- First submitted
- 2 Feb 2016
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Methylene Blue-based Combination Therapy in the Radical Treatment of Adult Patients With Plasmodium Vivax Malaria in Ethiopia: a Randomised Controlled Pilot Trial
- ClinicalTrials.gov ID
- NCT02696928
- Acronym / sponsor ID
- BlueAL / UniHD007
- Conditions
- Vivax Malaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of ethical approval in Ethiopia
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, Jimma University
- Study start
- Apr 2016
- Primary completion
- Oct 2017 (estimated)
- Study completion
- Jan 2018 (estimated)
- First posted
- 2 Mar 2016 (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.
Feasibility of methylene blue-based combination therapy in the radical treatment of adult patients with Plasmodium vivax malaria in Ethiopia: a randomised controlled pilot trial
Study rationale:
Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. Primaquine (PQ) is the only registered drug for radical cure of Plasmodium vivax malaria. Prolonged PQ-based combination therapy carries safety concerns and resistance to chloroquine (CQ) and PQ is emerging. Methylene blue (MB) has recently been shown to be safe and effective in the treatment of Plasmodium falciparum malaria in West Africa. As there is evidence for MB probably being effective against the hypnozoites of Plasmodium vivax, MB-based drug regimens could be an alternative to PQ-based combination therapy in Plasmodium vivax malaria.
Study objectives:
The main objective of this trial is to study the feasibility of MB-based combination therapy in patients with uncomplicated P. vivax malaria in an endemic area of Ethiopia.
Detailed description
The specific aims are (1) to test the feasibility and costs of methods and procedures for later use of MB-based combination therapy on a large scale, (2) to assess the safety of MB-based combination therapy, (3) to estimate the efficacy of MB-based combination therapy against malaria relapse, (4) to study the community acceptance of MB-based combination therapy, and (5) to strengthen the local capacity for malaria research and control in Jimma/Ethiopia.
Study design:
The study is designed as a pilot trial in adult patients with uncomplicated P. vivax malaria in Jimma, Ethiopia. Patients will be randomised to three treatment groups:
- Arthemeter/Lumefantrine (AL)
- AL-PQ, and
- AL-MB. Follow-up will be over a period of 6 months.
Study population:
Adult patients with uncomplicated P. vivax malaria (age ≥18 years) in Jimma/Ethiopia (G6PD deficient subjects are excluded) will become enrolled in the outpatient departments of the study centres. The sample size will be 33 per study arm, a total of 99 patients.
Study treatments:
- AL standard treatments twice daily (total of 80 mg/dose A plus 480 mg/dose L) over first three study days
- PQ 15 mg once daily for 14 days
- MB 780 mg once daily for 14 days Treatments will be 100% directly observed.
Study outcomes:
Outcome parameters will be on feasibility and costs (e.g. recruitment rates, retention rates, costs per patient), on safety parameters (e.g. haemoglobin development during follow-up, incidence of adverse events), on efficacy parameters (e.g. incidence of P. vivax relapse during follow-up, malaria recurrence-free efficacy until day 180), and on community acceptance (e.g. perceptions on blue urine) during follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Artemeter-Lumefantrine (combination therapy) | Other | Drug: Artemeter-Lumefantrine (combination therapy)33 patients (standard of care) |
| Artemeter-Lumefantrine and Primaquine (combination therapy) | Active comparator | Drug: Artemeter-Lumefantrine and Primaquine (combination therapy)33 patients |
| Artemeter-Lumefantrine and MB (combination therapy) | Experimental | Drug: Artemeter-Lumefantrine and MB (combination therapy)33 patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years
- Uncomplicated P. vivax monoinfection (asexual parasite count >250/µl)
- Axillary temperature ≥ 37.5°C or history of fever during last 48 hours
- Ability to tolerate oral drug therapy
- Written informed consent of patient
Key exclusion criteria (8 listed)
- Therapy with an antimalarial (e.g. CQ, amodiaquine, pyrimethamine-sulfadoxine, quinine, any ACT) or an antibiotic which is effective against malaria parasites (e.g. doxycyclin, clindamycin, CoTrim) during last three weeks
- Mixed malaria infection
- Clinical danger signals (e.g. unable to stand or to sit, unable to drink, repeated vomiting, convulsions) or signs and symptoms of severe malaria (according to WHO definition)
- Known other serious illnesses (e.g. cardiac, renal, hepatic, pulmonary disease, severe malnutrition, severe infectious diseases)
- G6PD deficiency (<60% activity, WHO classification 1-3)
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 |
|---|---|---|
| Artemeter-Lumefantrine and MB (combination therapy)Also: 3,7-bis(Dimethylamino)-phenothiazin-5-ium chloride, CID 6099AL first 3 days MB next 14 days | Drug | Artemeter-Lumefantrine and MB (combination therapy) |
| Artemeter-Lumefantrine (combination therapy)Also: ALAL first 3 days | Drug | Artemeter-Lumefantrine (combination therapy) |
| Artemeter-Lumefantrine and Primaquine (combination therapy)Also: AL and PQAL first 3 days PQ next 14 days | Drug | Artemeter-Lumefantrine and Primaquine (combination therapy) |
Primary outcome
Study feasibility
Time frame: 180 days
Patient recruitment rates
3 secondary outcomes
Incidence of P. vivax
Time frame: 180 days
Adverse events (AE) during total follow-up period
Time frame: 180 days
Study costs
Time frame: 180 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 25 Mar 2020.
- Individual participant dataSharing planned: Undecided
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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.
Olaf Müller, Prof. Dr. principal investigator
Heidelberg University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Artemeter-Lumefantrine and MB (combination therapy), Artemeter-Lumefantrine (combination therapy) and Artemeter-Lumefantrine and Primaquine (combination therapy) in people with Vivax Malaria, run by Heidelberg University.
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 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: withdrawn, as of the sponsor's last update on 25 Mar 2020. 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 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.
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?
Study feasibility (time frame: 180 days). 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 25 Mar 2020.