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)

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: Artemether-lumefantrine; Drug: Dihydroartemisinin-piperaquine

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 Type: Interventional
• Enrollment (Actual): 509
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tanzania
  • Kigoma
    • Ujiji, Kigoma, Tanzania, 255
      • Ujiji Health Centre
  • Tanga
    • Muheza, Tanga, Tanzania, 255
      • Muheza Disignated District Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Artemether-lumefantrine	Drug: Artemether-lumefantrine; Artemether-lumefantrine; Other Names: A
Experimental: B; Dihydroartemisinin-piperaquine	Drug: Dihydroartemisinin-piperaquine; Dihydroartemisinin-piperaquine; Other Names: B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
parasitological cure on day 28 for ALu and 42 for DHA-PQ	non-adjusted and adjusted by PCR to account for new infections.	42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
parasite clearance after 72 hours.	Microscope Blood slide for malaria reading 0 parasite.	72 hours
parasitological cure on day 14	Microscope Blood slide for malaria reading 0 parasite.	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.	63 days
improvement in haemoglobin level at day 28 from the day 0 baseline		28 days
reduction in gametocyte carriage at day 14 and day 28 from the day 0 baseline,		28 days
occurrence and severity of adverse events and genomic profile of P.falciparum.		63 days

Collaborators and Investigators

• Sponsor: National Institute for Medical Research, Tanzania
• Collaborators: World Health Organization; Ministry of Health and Social Welfare, Tanzania
• Investigators: Principal Investigator: Deus Ishengoma, PHD, National Institute for Medical Research; Study Director: Celine Mandara, MD, Msc, National Institute for Medical Research

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 13, 2014
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Actual): December 26, 2017
• Last Update Submitted That Met QC Criteria: December 22, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Parasite clearance, Treatment failure
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Lumefantrine; Artemether; Artemether, Lumefantrine Drug Combination; Piperaquine; Artenimol
• Other Study ID Numbers: WB-Malaria- Tanzania.