MalariaPhase 4WB-MalariaNCT02590627
In-vivo Efficacy and Safety of Artemether/Lumefantrine Vs Dihydroartemisinin-piperaquine for Treatment of Uncomplicated Malaria and Assessment of Parasite Genetic Factors Associated With Parasite Clearance or Treatment Failure
A Phase 4 study testing Artemether-lumefantrine and Dihydroartemisinin-piperaquine in people with Malaria, run by National Institute for Medical Research, Tanzania at 2 sites in Tanzania.
Trial summary
Drug efficacy testing is one of the most important tasks that is routinely undertaken by the National Malaria Control Program (NMCP) in Tanzania and has been recommended by the World health Organisation to monitor the efficacy of artemisinin based combination therapy (ACT) and possibly detect evolution/emergency of… Read more about this study
- Who is it for?
- Ages 6 months to 10 years
- Conditions the study is for
- Malaria
- What is being tested?
- Artemether-lumefantrine and Dihydroartemisinin-piperaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 509 participants
- Where
- 2 sitesTanzania
- Study dates
- May 2014to Dec 2015
- Phase
- Phase 4
- 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 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients aged between 6 months - 10 years, without severe malnutrition and with a slide-confirmed mono-infection of P. falciparum, and asexual parasitemia between 250 - 200000 asexual parasites/µl will be included.
- Other inclusion criteria will include, absence of dangers signs (see Exclusion Criteria), axillary temperature > 37.5oC or a history of fever within the past 24 hours and ability to swallow oral medications.
- The ability and willingness to attend scheduled follow-up visits and an informed consent provided by parent or guardian will also be considered as important inclusion criteria without which a patient will not be enrolled into the study.
- Patients shall not be excluded on the basis of reported prior treatment with other anti-malarial drugs other than DHA-PQ within the past 24 hours if they have fever (axillary temperature > 37.50C) and parasitemia.
- Patients should have stable residence within the catchment area throughout the study period
Who cannot join
- The exclusion criteria will include: presence of general danger signs or signs of severe falciparum malaria according to the definitions of WHO (Appendix 6), severe anaemia (Hb < 5 g/dL) and mixed or mono-infection with species other the P. falciparum.
- Others will include severe malnutrition (defined as a child whose growth standard is below -3 z-score or symmetrical oedema involving at least one of the feet or a mid-upper arm circumference < 110 mm.
- Patients with febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases and HIV/AIDS) will be excluded.
- Furthermore, patients under regular medication, which may interfere with anti-malarial pharmacokinetics and those with a history of hypersensitivity reactions or contraindications to the artemisinin-based therapy, piperaquine or the alternative treatment, will not be included into the study
Trial locations and contacts
2 sites in 1 country.
Tanzania2 sites
Muheza Disignated District Hospital
Muheza, Tanga, 255
Ujiji Health Centre
Ujiji, Kigoma Region, 255
About this study
Drug efficacy testing is one of the most important tasks that is routinely undertaken by the National Malaria Control Program (NMCP) in Tanzania and has been recommended by the World health Organisation to monitor the efficacy of artemisinin based combination therapy (ACT) and possibly detect evolution/emergency of tolerance/resistance to these drugs. Currently, Artemether-lumefantrine (ALu) is the only ACT recommended by the Ministry of Health and Social Welfare and therefore testing of new ACTs such as dihydroartemisinin-piperaquine (DHA-PQ) is important because alternative drugs are urgently required. Meanwhile, NMCP is revising the guidelines for treatment of malaria in Tanzania and DHA-PQ has been earmarked as an alternative ACT to be used together with ALu. However, efficacy and safety data of DHA-PQ is missing since no studies have been done in Tanzania. Thus, a study is proposed to assess the efficacy and safety of DHA-PQ Vs ALu and provide important data which will enable the NMCP to make informed decisions; and possibly recommend DHA-PQ in the new Malaria treatment guidelines as the second line drug for the treatment of uncomplicated malaria in the country.
Read the detailed description
Currently, Artemether-lumefantrine (ALu) is the only ACT recommended by the Ministry of Health and Social Welfare and therefore testing of new ACTs such as dihydroartemisinin-piperaquine (DHA-PQ) is important because alternative drugs are urgently required. Meanwhile, NMCP is revising the guidelines for treatment of malaria in Tanzania and DHA-PQ has been earmarked as an alternative ACT to be used together with ALu. However, efficacy and safety data of DHA-PQ is missing since no studies have been done in Tanzania. Thus, a study is proposed to assess the efficacy and safety of DHA-PQ Vs ALu and provide important data which will enable the NMCP to make informed decisions; and possibly recommend DHA-PQ in the new Malaria treatment guidelines as the second line drug for the treatment of uncomplicated malaria in the country.
- Conditions
- Malaria
- Being tested
- Artemether-lumefantrine, Dihydroartemisinin-piperaquine
- Keywords
- Parasite clearance, Treatment failure
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrineDrug
Also called A
Artemether-lumefantrine
Dihydroartemisinin-piperaquineDrug
Also called B
Dihydroartemisinin-piperaquine
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Artemether-lumefantrine Receives: Drug: Artemether-lumefantrine |
| B | Experimental | Dihydroartemisinin-piperaquine Receives: Drug: Dihydroartemisinin-piperaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
parasitological cure on day 28 for ALu and 42 for DHA-PQ
non-adjusted and adjusted by PCR to account for new infections.
Measured: 42 days
Secondary outcomes (6)
parasite clearance after 72 hours.
Microscope Blood slide for malaria reading 0 parasite.
Measured: 72 hours
parasitological cure on day 14
Microscope Blood slide for malaria reading 0 parasite.
Measured: 14 days
extended parasitological cure on day 42 for ALu and 63 for DHA-PQ
PCR and Microscope Blood slide for malaria parasitemia reading 0.
Measured: 63 days
improvement in haemoglobin level at day 28 from the day 0 baseline
Measured: 28 days
reduction in gametocyte carriage at day 14 and day 28 from the day 0 baseline,
Measured: 28 days
occurrence and severity of adverse events and genomic profile of P.falciparum.
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 posted29 Oct 2015 (estimated)
- Study startMay 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 509 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute for Medical Research, Tanzania
- Sponsor type
- Other government
- Collaborators
- Ministry of Health and Social Welfare, Tanzania, World Health Organization
- Responsible party
- Principal investigator, Dr. Geofrey Makenga, National Institute for Medical Research, Tanzania
- Investigators
- Deus Ishengoma, PHD, Principal investigator, National Institute for Medical ResearchCeline Mandara, MD, Msc, Study director, National Institute for Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02590627
- Sponsor's protocol ID
- WB-Malaria- Tanzania.
- Acronym
- WB-Malaria
- Status last verified
- Dec 2017
- First submitted
- 13 Jul 2014
- Last updated
- 26 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Mandara CI, Kavishe RA, Gesase S, Mghamba J, Ngadaya E, Mmbuji P, Mkude S, Mandike R, Njau R, Mohamed A, Lemnge MM, Warsame M, Ishengoma DS. High efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Muheza and Kigoma Districts, Tanzania. Malar J. 2018 Jul 11;17(1):261. doi: 10.1186/s12936-018-2409-z.
PubMed 29996849
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In-vivo Efficacy and Safety of Artemether/Lumefantrine Vs Dihydroartemisinin-piperaquine for Treatment of Uncomplicated Malaria and Assessment of Parasite Genetic Factors Associated With Parasite Clearance or Treatment Failure
- ClinicalTrials.gov ID
- NCT02590627
- Acronym / sponsor ID
- WB-Malaria / WB-Malaria- Tanzania.
- Conditions
- Malaria
- Keywords
- Parasite clearance, Treatment failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 509 participants (actual)
- Lead sponsor
- National Institute for Medical Research, TanzaniaOther government
- Collaborators
- Ministry of Health and Social Welfare, Tanzania, World Health Organization
- Study start
- May 2014 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 29 Oct 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.
Drug efficacy testing is one of the most important tasks that is routinely undertaken by the National Malaria Control Program (NMCP) in Tanzania and has been recommended by the World health Organisation to monitor the efficacy of artemisinin based combination therapy (ACT) and possibly detect evolution/emergency of tolerance/resistance to these drugs. Currently, Artemether-lumefantrine (ALu) is the only ACT recommended by the Ministry of Health and Social Welfare and therefore testing of new ACTs such as dihydroartemisinin-piperaquine (DHA-PQ) is important because alternative drugs are urgently required. Meanwhile, NMCP is revising the guidelines for treatment of malaria in Tanzania and DHA-PQ has been earmarked as an alternative ACT to be used together with ALu. However, efficacy and safety data of DHA-PQ is missing since no studies have been done in Tanzania. Thus, a study is proposed to assess the efficacy and safety of DHA-PQ Vs ALu and provide important data which will enable the NMCP to make informed decisions; and possibly recommend DHA-PQ in the new Malaria treatment guidelines as the second line drug for the treatment of uncomplicated malaria in the country.
Detailed description
Currently, Artemether-lumefantrine (ALu) is the only ACT recommended by the Ministry of Health and Social Welfare and therefore testing of new ACTs such as dihydroartemisinin-piperaquine (DHA-PQ) is important because alternative drugs are urgently required. Meanwhile, NMCP is revising the guidelines for treatment of malaria in Tanzania and DHA-PQ has been earmarked as an alternative ACT to be used together with ALu. However, efficacy and safety data of DHA-PQ is missing since no studies have been done in Tanzania. Thus, a study is proposed to assess the efficacy and safety of DHA-PQ Vs ALu and provide important data which will enable the NMCP to make informed decisions; and possibly recommend DHA-PQ in the new Malaria treatment guidelines as the second line drug for the treatment of uncomplicated malaria in the country.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Artemether-lumefantrineArtemether-lumefantrine |
| B | Experimental | Drug: Dihydroartemisinin-piperaquineDihydroartemisinin-piperaquine |
Who may qualify
- Ages
- 6 months to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Patients aged between 6 months - 10 years, without severe malnutrition and with a slide-confirmed mono-infection of P. falciparum, and asexual parasitemia between 250 - 200000 asexual parasites/µl will be included.
- Other inclusion criteria will include, absence of dangers signs (see Exclusion Criteria), axillary temperature > 37.5oC or a history of fever within the past 24 hours and ability to swallow oral medications.
- The ability and willingness to attend scheduled follow-up visits and an informed consent provided by parent or guardian will also be considered as important inclusion criteria without which a patient will not be enrolled into the study.
- Patients shall not be excluded on the basis of reported prior treatment with other anti-malarial drugs other than DHA-PQ within the past 24 hours if they have fever (axillary temperature > 37.50C) and parasitemia.
- Patients should have stable residence within the catchment area throughout the study period
Key exclusion criteria (4 listed)
- The exclusion criteria will include: presence of general danger signs or signs of severe falciparum malaria according to the definitions of WHO (Appendix 6), severe anaemia (Hb < 5 g/dL) and mixed or mono-infection with species other the P. falciparum.
- Others will include severe malnutrition (defined as a child whose growth standard is below -3 z-score or symmetrical oedema involving at least one of the feet or a mid-upper arm circumference < 110 mm.
- Patients with febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases and HIV/AIDS) will be excluded.
- Furthermore, patients under regular medication, which may interfere with anti-malarial pharmacokinetics and those with a history of hypersensitivity reactions or contraindications to the artemisinin-based therapy, piperaquine or the alternative treatment, will not be included into the study
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 |
|---|---|---|
| Artemether-lumefantrineAlso: AArtemether-lumefantrine | Drug | A |
| Dihydroartemisinin-piperaquineAlso: BDihydroartemisinin-piperaquine | Drug | B |
Primary outcome
parasitological cure on day 28 for ALu and 42 for DHA-PQ
Time frame: 42 days
non-adjusted and adjusted by PCR to account for new infections.
6 secondary outcomes
parasite clearance after 72 hours.
Time frame: 72 hours
parasitological cure on day 14
Time frame: 14 days
extended parasitological cure on day 42 for ALu and 63 for DHA-PQ
Time frame: 63 days
improvement in haemoglobin level at day 28 from the day 0 baseline
Time frame: 28 days
reduction in gametocyte carriage at day 14 and day 28 from the day 0 baseline,
Time frame: 28 days
occurrence and severity of adverse events and genomic profile of P.falciparum.
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 26 Dec 2017.
- Derived from this study: PubMed 29996849Mandara CI, Kavishe RA, Gesase S, Mghamba J, Ngadaya E, Mmbuji P, Mkude S, Mandike R, Njau R, Mohamed A, Lemnge MM, Warsame M, Ishengoma DS. High efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Muheza and Kigoma Districts, Tanzania. Malar J. 2018 Jul 11;17(1):261. doi: 10.1186/s12936-018-2409-z.
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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.
Deus Ishengoma, PHD principal investigator
National Institute for Medical Research
Celine Mandara, MD, Msc study director
National Institute for Medical Research
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artemether-lumefantrine and Dihydroartemisinin-piperaquine in people with Malaria, run by National Institute for Medical Research, Tanzania at 2 sites in Tanzania.
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 5 inclusion and 4 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 26 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Tanzania. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
parasitological cure on day 28 for ALu and 42 for DHA-PQ (time frame: 42 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 NCT02590627, 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 26 Dec 2017.