Methylene Blue Against Vivax Malaria in Ethiopia (BlueAL)
Primary Purpose
Vivax Malaria
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Artemeter-Lumefantrine and MB (combination therapy)
Artemeter-Lumefantrine (combination therapy)
Artemeter-Lumefantrine and Primaquine (combination therapy)
Sponsored by
About this trial
This is an interventional treatment trial for Vivax Malaria
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Active Comparator
Experimental
Arm Label
Artemeter-Lumefantrine (combination therapy)
Artemeter-Lumefantrine and Primaquine (combination therapy)
Artemeter-Lumefantrine and MB (combination therapy)
Arm Description
33 patients (standard of care)
33 patients
33 patients
Outcomes
Primary Outcome Measures
Study feasibility
Patient recruitment rates
Secondary Outcome Measures
Incidence of P. vivax
Passive and active surveillance
Adverse events (AE) during total follow-up period
Passive and active surveillance
Study costs
Costs per patient
Full Information
NCT ID
NCT02696928
First Posted
February 2, 2016
Last Updated
March 23, 2020
Sponsor
Heidelberg University
Collaborators
Ludwig-Maximilians - University of Munich, Jimma University
1. Study Identification
Unique Protocol Identification Number
NCT02696928
Brief Title
Methylene Blue Against Vivax Malaria in Ethiopia
Acronym
BlueAL
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of ethical approval in Ethiopia
Study Start Date
April 2016 (undefined)
Primary Completion Date
October 2017 (Anticipated)
Study Completion Date
January 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Heidelberg University
Collaborators
Ludwig-Maximilians - University of Munich, Jimma University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vivax Malaria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Artemeter-Lumefantrine (combination therapy)
Arm Type
Other
Arm Description
33 patients
(standard of care)
Arm Title
Artemeter-Lumefantrine and Primaquine (combination therapy)
Arm Type
Active Comparator
Arm Description
33 patients
Arm Title
Artemeter-Lumefantrine and MB (combination therapy)
Arm Type
Experimental
Arm Description
33 patients
Intervention Type
Drug
Intervention Name(s)
Artemeter-Lumefantrine and MB (combination therapy)
Other Intervention Name(s)
3,7-bis(Dimethylamino)-phenothiazin-5-ium chloride, CID 6099
Intervention Description
AL first 3 days MB next 14 days
Intervention Type
Drug
Intervention Name(s)
Artemeter-Lumefantrine (combination therapy)
Other Intervention Name(s)
AL
Intervention Description
AL first 3 days
Intervention Type
Drug
Intervention Name(s)
Artemeter-Lumefantrine and Primaquine (combination therapy)
Other Intervention Name(s)
AL and PQ
Intervention Description
AL first 3 days PQ next 14 days
Primary Outcome Measure Information:
Title
Study feasibility
Description
Patient recruitment rates
Time Frame
180 days
Secondary Outcome Measure Information:
Title
Incidence of P. vivax
Description
Passive and active surveillance
Time Frame
180 days
Title
Adverse events (AE) during total follow-up period
Description
Passive and active surveillance
Time Frame
180 days
Title
Study costs
Description
Costs per patient
Time Frame
180 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olaf Müller, Prof. Dr.
Organizational Affiliation
Heidelberg University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Methylene Blue Against Vivax Malaria in Ethiopia
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