Malaria, FalciparumPhase 2BlueACTnNCT02851108
Methylene Blue Against Falciparum Malaria in Burkina Faso
A Phase 2 study testing Methylene Blue and Primaquine in people with Malaria, Falciparum, run by Heidelberg University at 1 site in Burkina Faso.
Trial summary
Safety of artesunate-amodiaquine combined with methylene blue or primaquine for falciparum malaria treatment in African children: A randomised controlled trial 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 6 to 59 months
- Conditions the study is for
- Malaria, Falciparum
- What is being tested?
- Methylene Blue and Primaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteBurkina Faso
- Study dates
- Oct 2016to Feb 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Weight ≥ 6 kg
- Uncomplicated malaria caused by P. falciparum
- Asexual parasites ≥ 2 000/µl and ≤ 100 000/µl
- Axillary temperature ≥ 37.5°C or a history of fever during the last 24 hours
- Burkinabe nationality
- Permanent residence in the study area with no intention of leaving during the surveillance period
- Written informed consent of parents or care takers
Who cannot join
- Severe malaria
- Mixed malaria infection
- Vomiting (>2 times within 24 hours before the visit)
- Any apparent significant disease, including severe malnutrition
- A history of a previous, significant adverse reaction or known allergy to one or more of the study drugs
- Anaemia (haemoglobin < 7 g/dl)
Show all 12Show fewer
- Treated in the same trial before
- All modern antimalarial treatment prior to inclusion (last seven days)
- Therapy with serotonin reuptake inhibitors (e.g. citalopram, escitalopram, fluoxetine, Paroxetine, Sertraline)
- Simultaneous participation in another investigational study
- Patients with known HIV/AIDS disease
- Therapy with drugs known to inhibit the liver enzymes cytochrome 2A6 (e.g. methoxsalen, pilocarpine, tranylcypromine) and/or cytochrome 2C8 (e.g. trimethoprim, ketoconazole, ritonavir, saquinavir, lopinavir, gemfibrozil, montelukast)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety of Artesunate-amodiaquine Combined With Methylene Blue or Primaquine for Falciparum Malaria Treatment in African Children: A Randomised Controlled Trial
Safety of artesunate-amodiaquine combined with methylene blue or primaquine for falciparum malaria treatment in African children: A randomised controlled trial
Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. As resistance against artemisinin compounds has recently started to emerge in South-East Asia, there is a clear need to develop alternative malaria drug combinations. Adding another anti-malarial with a short half-life such as methylene blue to standard ACT (artemisinin-based combination therapy) could be a strategy to prevent artemisinin resistance development. Moreover, adding a gametocytocidal drug to ACT reduces the probability of transmission of P. falciparum parasites including drug-resistant parasites.
Objectives: The primary objective of this trial is to investigate the safety of artesunate (AS) - amodiaquine (AQ) - methylene blue (MB) compared to AS - AQ - primaquine (PQ) in young children with uncomplicated falciparum malaria in Burkina Faso.
Read the detailed description
The overall goal of the underlying research project is to develop a MB-based first-line drug combination regimen against uncomplicated falciparum malaria in SSA.
The primary objective of this study is: To study the safety of the triple combination AS-AQ-MB compared to AS-AQ-PQ in the treatment of uncomplicated falciparum malaria in young African children. The secondary objective of this study is: To study the efficacy of this MB-based triple combination in comparison with standard ACT-PQ in the treatment of uncomplicated falciparum malaria in young African children.
It is a mono-center, open randomised controlled non-inferiority study in children with uncomplicated falciparum malaria in Burkina Faso. Patients will be randomised to two treatment groups (arms):
- AS-AQ-MB
- AS-AQ-PQ
Study population: Children aged 6-59 months with uncomplicated falciparum malaria from Nouna Hospital in north-western Burkina Faso.
Sample size: 100 patients (50 per study arm).
Treatment: The group AS-AQ-MB will receive once daily a fixed dose AS-AQ formulation combined with once daily MB (15 mg/kg) over a three days period. The control group will receive once daily a fixed dose AS-AQ over three days combined with a single dose of PQ on day 2 (0.25 mg/kg).
Endpoints: Primary endpoint is the haemoglobin value on day 7 compared to baseline. Secondary endpoints are adverse events (AE), adequate clinical and parasitological response (ACPR) rate (PCR-corrected for recrudescences), as well as gametocyte prevalence and density.
- Conditions
- Malaria, Falciparum
- Being tested
- Methylene Blue, Primaquine
- Keywords
- falciparum malaria, sub saharan, africa, elimination disorder
- Medical subject headings
- Malaria, Falciparum, Elimination Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene BlueDrug
Also called 3,7-bis(Dimethylamino)-phenothiazine-5-ium chloride
50 patients will receive methylene blue
PrimaquineDrug
Also called (±)-N4-(6-Methoxychinolin-8-yl)pentan-1,4-diamine
50 patients will receive primaquine
| Study group | Role | What they receive |
|---|---|---|
| AS-AQ-MB | Experimental | Once daily a fixed dose artesunate-amodiaquine formulation combined with once daily methylene blue (15 mg/kg) over a three days period. Receives: Drug: Methylene Blue |
| AS-AQ-PQ | Active comparator | Once daily a fixed dose artesunate-amodiaquine over three days combined with a single dose of primaquine on day 2 (0.25 mg/kg). Receives: Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Haemoglobin Compared to the Baseline
Haemoglobin concentrations will be measured in the field using a HemoCue® (HemoCue® AB, Angelholm, Sweden)
Measured: 7 days
Secondary outcomes (4)
Gametocyte Prevalence
measured microscopically at baseline and on day 1, 2, 3, 7, 14, and 28 of follow-up
Measured: 28 days
Adverse Events (AE)
Reports of observed or self-reported adverse event
Measured: 28 days
Mothers/Caretakers Questionnaire on Acceptance
Acceptance of the different treatment regimens by mothers/caretakers
Measured: 14 days
Gametocyte Density
measured microscopically at baseline and on day 1, 2, 3, 7, 14, and 28 of follow-up
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2016 (estimated)
- Study startOct 2016
- Primary completionDec 2016
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malaria, FalciparumStudies 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
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche en Sante de Nouna, Burkina Faso
- Responsible party
- Principal investigator, Olaf Mueller, Heidelberg University
- Investigators
- Olaf Müller, Prof. Dr., Principal investigator, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02851108
- Sponsor's protocol ID
- UniHD008
- Acronym
- BlueACTn
- Status last verified
- Mar 2020
- First submitted
- 28 Jun 2016
- Last updated
- 25 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Mendes Jorge M, Ouermi L, Meissner P, Compaore G, Coulibaly B, Nebie E, Krisam J, Klose C, Kieser M, Jahn A, Lu G, D Alessandro U, Sie A, Mockenhaupt FP, Muller O. Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. PLoS One. 2019 Oct 10;14(10):e0222993. doi: 10.1371/journal.pone.0222993. eCollection 2019.
PubMed 31600221
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
- Safety of Artesunate-amodiaquine Combined With Methylene Blue or Primaquine for Falciparum Malaria Treatment in African Children: A Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT02851108
- Acronym / sponsor ID
- BlueACTn / UniHD008
- Conditions
- Malaria, Falciparum
- Keywords
- falciparum malaria, sub saharan, africa, elimination disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Collaborators
- Centre de Recherche en Sante de Nouna, Burkina Faso
- Study start
- Oct 2016 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 1 Aug 2016 (estimated)
- Results
- Posted 25 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Safety of artesunate-amodiaquine combined with methylene blue or primaquine for falciparum malaria treatment in African children: A randomised controlled trial
Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. As resistance against artemisinin compounds has recently started to emerge in South-East Asia, there is a clear need to develop alternative malaria drug combinations. Adding another anti-malarial with a short half-life such as methylene blue to standard ACT (artemisinin-based combination therapy) could be a strategy to prevent artemisinin resistance development. Moreover, adding a gametocytocidal drug to ACT reduces the probability of transmission of P. falciparum parasites including drug-resistant parasites.
Objectives: The primary objective of this trial is to investigate the safety of artesunate (AS) - amodiaquine (AQ) - methylene blue (MB) compared to AS - AQ - primaquine (PQ) in young children with uncomplicated falciparum malaria in Burkina Faso.
Detailed description
The overall goal of the underlying research project is to develop a MB-based first-line drug combination regimen against uncomplicated falciparum malaria in SSA.
The primary objective of this study is: To study the safety of the triple combination AS-AQ-MB compared to AS-AQ-PQ in the treatment of uncomplicated falciparum malaria in young African children. The secondary objective of this study is: To study the efficacy of this MB-based triple combination in comparison with standard ACT-PQ in the treatment of uncomplicated falciparum malaria in young African children.
It is a mono-center, open randomised controlled non-inferiority study in children with uncomplicated falciparum malaria in Burkina Faso. Patients will be randomised to two treatment groups (arms):
- AS-AQ-MB
- AS-AQ-PQ
Study population: Children aged 6-59 months with uncomplicated falciparum malaria from Nouna Hospital in north-western Burkina Faso.
Sample size: 100 patients (50 per study arm).
Treatment: The group AS-AQ-MB will receive once daily a fixed dose AS-AQ formulation combined with once daily MB (15 mg/kg) over a three days period. The control group will receive once daily a fixed dose AS-AQ over three days combined with a single dose of PQ on day 2 (0.25 mg/kg).
Endpoints: Primary endpoint is the haemoglobin value on day 7 compared to baseline. Secondary endpoints are adverse events (AE), adequate clinical and parasitological response (ACPR) rate (PCR-corrected for recrudescences), as well as gametocyte prevalence and density.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AS-AQ-MB | Experimental | Drug: Methylene BlueOnce daily a fixed dose artesunate-amodiaquine formulation combined with once daily methylene blue (15 mg/kg) over a three days period. |
| AS-AQ-PQ | Active comparator | Drug: PrimaquineOnce daily a fixed dose artesunate-amodiaquine over three days combined with a single dose of primaquine on day 2 (0.25 mg/kg). |
Who may qualify
- Ages
- 6 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Weight ≥ 6 kg
- Uncomplicated malaria caused by P. falciparum
- Asexual parasites ≥ 2 000/µl and ≤ 100 000/µl
- Axillary temperature ≥ 37.5°C or a history of fever during the last 24 hours
- Burkinabe nationality
Key exclusion criteria (12 listed)
- Severe malaria
- Mixed malaria infection
- Vomiting (>2 times within 24 hours before the visit)
- Any apparent significant disease, including severe malnutrition
- A history of a previous, significant adverse reaction or known allergy to one or more of the study drugs
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 |
|---|---|---|
| Methylene BlueAlso: 3,7-bis(Dimethylamino)-phenothiazine-5-ium chloride50 patients will receive methylene blue | Drug | AS-AQ-MB |
| PrimaquineAlso: (±)-N4-(6-Methoxychinolin-8-yl)pentan-1,4-diamine50 patients will receive primaquine | Drug | AS-AQ-PQ |
Primary outcome
Change in Haemoglobin Compared to the Baseline
Time frame: 7 days
Haemoglobin concentrations will be measured in the field using a HemoCue® (HemoCue® AB, Angelholm, Sweden)
4 secondary outcomes
Gametocyte Prevalence
Time frame: 28 days
Adverse Events (AE)
Time frame: 28 days
Mothers/Caretakers Questionnaire on Acceptance
Time frame: 14 days
Gametocyte Density
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31600221Mendes Jorge M, Ouermi L, Meissner P, Compaore G, Coulibaly B, Nebie E, Krisam J, Klose C, Kieser M, Jahn A, Lu G, D Alessandro U, Sie A, Mockenhaupt FP, Muller O. Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. PLoS One. 2019 Oct 10;14(10):e0222993. doi: 10.1371/journal.pone.0222993. eCollection 2019.
- 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylene Blue and Primaquine in people with Malaria, Falciparum, run by Heidelberg University at 1 site in Burkina Faso.
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 7 inclusion and 12 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 25 Mar 2020. 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 Burkina Faso. 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 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?
Yes. Results are posted in the registry (first posted 25 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Haemoglobin Compared to the Baseline (time frame: 7 days). 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 NCT02851108, which also lists 1 linked publication.
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.