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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 (WB-Malaria)

Primary Purpose

Malaria

Status

Completed

Phase

Phase 4

Locations

Tanzania

Study Type

Interventional

Intervention

Artemether-lumefantrine

Dihydroartemisinin-piperaquine

About this trial

This is an interventional treatment trial for Malaria focused on measuring Parasite clearance, Treatment failure

Eligibility Criteria

6 Months - 10 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Ujiji Health Centre
Muheza Disignated District Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm Description

Artemether-lumefantrine

Dihydroartemisinin-piperaquine

Outcomes

Primary Outcome Measures

parasitological cure on day 28 for ALu and 42 for DHA-PQ

non-adjusted and adjusted by PCR to account for new infections.

Secondary Outcome Measures

parasite clearance after 72 hours.

Microscope Blood slide for malaria reading 0 parasite.

parasitological cure on day 14

Microscope Blood slide for malaria reading 0 parasite.

extended parasitological cure on day 42 for ALu and 63 for DHA-PQ

PCR and Microscope Blood slide for malaria parasitemia reading 0.

improvement in haemoglobin level at day 28 from the day 0 baseline

reduction in gametocyte carriage at day 14 and day 28 from the day 0 baseline,

occurrence and severity of adverse events and genomic profile of P.falciparum.

Full Information

NCT ID

NCT02590627

First Posted

July 13, 2014

Last Updated

December 22, 2017

Sponsor

National Institute for Medical Research, Tanzania

Collaborators

Ministry of Health and Social Welfare, Tanzania, World Health Organization

1. Study Identification

Unique Protocol Identification Number

NCT02590627

Brief 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

Acronym

WB-Malaria

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Completed

Study Start Date

May 2014 (Actual)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Institute for Medical Research, Tanzania

Collaborators

Ministry of Health and Social Welfare, Tanzania, World Health Organization

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria

Keywords

Parasite clearance, Treatment failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

509 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Artemether-lumefantrine

Arm Title

Arm Type

Experimental

Arm Description

Dihydroartemisinin-piperaquine

Intervention Type

Drug

Intervention Name(s)

Artemether-lumefantrine

Other Intervention Name(s)

Intervention Description

Artemether-lumefantrine

Intervention Type

Drug

Intervention Name(s)

Dihydroartemisinin-piperaquine

Other Intervention Name(s)

Intervention Description

Dihydroartemisinin-piperaquine

Primary Outcome Measure Information:

Title

parasitological cure on day 28 for ALu and 42 for DHA-PQ

Description

non-adjusted and adjusted by PCR to account for new infections.

Time Frame

42 days

Secondary Outcome Measure Information:

Title

parasite clearance after 72 hours.

Description

Microscope Blood slide for malaria reading 0 parasite.

Time Frame

72 hours

Title

parasitological cure on day 14

Description

Microscope Blood slide for malaria reading 0 parasite.

Time Frame

14 days

Title

extended parasitological cure on day 42 for ALu and 63 for DHA-PQ

Description

PCR and Microscope Blood slide for malaria parasitemia reading 0.

Time Frame

63 days

Title

improvement in haemoglobin level at day 28 from the day 0 baseline

Time Frame

28 days

Title

reduction in gametocyte carriage at day 14 and day 28 from the day 0 baseline,

Time Frame

28 days

Title

occurrence and severity of adverse events and genomic profile of P.falciparum.

Time Frame

63 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

10 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Deus Ishengoma, PHD

Organizational Affiliation

National Institute for Medical Research

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Celine Mandara, MD, Msc

Organizational Affiliation

National Institute for Medical Research

Official's Role

Study Director

Facility Information:

Facility Name

Ujiji Health Centre

City

Ujiji

State/Province

Kigoma

ZIP/Postal Code

255

Country

Tanzania

Facility Name

Muheza Disignated District Hospital

City

Muheza

State/Province

Tanga

ZIP/Postal Code

255

Country

Tanzania

12. IPD Sharing Statement

Citations:

PubMed Identifier

29996849

Citation

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.

Results Reference

derived

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