Efficacy and Safety of ASAQ and PD for the Treatment of Uncomplicated Falciparum Malaria in Mainland Tanzania (GF-TES-2017)

Efficacy and Safety of Artesunate-amodiaquine and Dihydroartemisinin-piperaquine for the Treatment of Uncomplicated Falciparum Malaria in Mainland Tanzania

The World Health Organization recommends regular surveillance of antimalarial efficacy to monitor the performance of different drugs. The Tanzanian National Malaria Control Programme (NMCP) in collaboration with its partners have been implementing therapeutic efficacy studies (TES) to monitor the performance of different antimalarials in the country. Most of the studies conducted in recent years focused on artemether-lumefantrine which is the first line antimalarial for the treatment of uncomplicated malaria in Mainland Tanzania. However, data on the performance of other artemisinin based combination therapy (ACTs) is urgently needed to support timely review and changes of treatment guidelines in case of drug resistance to current regimen. This study was undertaken in the same NMCP framework to assess the efficacy and safety of alternative ACTs used or with potential use in Tanzania. The study assessed the efficacy and safety of artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DP) for the treatment of uncomplicated malaria in Tanzania. The study was undertaken at two NMCP sentinel sites of Kibaha and Ujiji from July to December 2017.

Study Overview

• Status: Completed
• Conditions: Uncomplicated Falciparum Malaria
• Intervention / Treatment: Drug: Artesunate amodiaquine

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tanzania
  • Tanga, Tanzania
    • National Institute for Medical Research

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 6 months to 10 years.
• mono-infection with P. falciparum detected by microscopy;
• parasitaemia of 250 - 200,000/μl asexual forms;
• presence of axillary temperature ≥37.5 °C or history of fever during the past 24 hours
• ability to swallow oral medication;
• ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; and
• Informed consent from the parents or guardians of children.

Exclusion Criteria:

• mRDT negative
• presence of general danger signs in children aged 6 months to 10 years or signs of severe falciparum malaria according to the definitions of WHO (Appendix 1);
• weight under 5 Kg
• mixed or mono-infection with another Plasmodium species detected by microscopy;
• presence of severe malnutrition (defined as a child who has symmetrical oedema involving at least the feet or has a mid-upper arm circumference < 110 mm in children ≤ 59 months; or BMI of <16 in children aged 5 years and above)
• presence of 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, HIV/AIDS);
• regular medication, which may interfere with antimalarial pharmacokinetics;
• history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: single arm; Artesunate amodiaquine tablets containing 25/67.5 mg, 50/135mg and 100/270 mg base of artesunate-amodiaquine were administered according to body weight Dihrdroartemisinin piperaquine tablets containing 160/20mg and 320/40mg base of piperaquine dihydroartemisinin were administered according to body weight	Drug: Artesunate amodiaquine; Drugs were administered under observation of the study nurse for three days; Other Names: dihydroartemisinin piperaquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adequate clinical response	Proportions of patients with 100% cure before PCR correction	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCR corrected responses	Proportions of patients with 100% cure after PCR correction	one months after study completion

Collaborators and Investigators

• Sponsor: National Institute for Medical Research, Tanzania
• Collaborators: World Health Organization; Muhimbili University of Health and Allied Sciences
• Investigators: Principal Investigator: Deus S Ishengoma, PhD, National Institute for Medical Research

Publications and helpful links

General Publications

• Mandara CI, Francis F, Chiduo MG, Ngasala B, Mandike R, Mkude S, Chacky F, Molteni F, Njau R, Mohamed A, Warsame M, Ishengoma DS. High cure rates and tolerability of artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Kibaha and Kigoma, Tanzania. Malar J. 2019 Mar 25;18(1):99. doi: 10.1186/s12936-019-2740-z.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2017
• Primary Completion (Actual): December 8, 2017
• Study Completion (Actual): December 8, 2017

Study Registration Dates

• First Submitted: December 22, 2017
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 13, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Artesunate; Piperaquine; Amodiaquine; Artenimol
• Other Study ID Numbers: NIMR-Tanzania

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No