The Transmission of Artemisinin Resistant Parasites Before and After Conventional Artemisinin-combination Therapy
SPARTAN
1 other identifier
interventional
120
1 country
2
Brief Summary
A prospective study will be carried out in an area where parasites with reduced sensitivity to malaria drugs (artemisinins) have recently emerged. The study will recruit participants from patients who attend the clinic with uncomplicated malaria and asymptomatically infected individuals. Participants are treated with conventional artemisinin-combination therapies (ACT) as part of standard clinical care. From this population, we will select P. falciparum gametocyte carriers. Before, during and after ACT treatment, the transmission potential of artemisinin resistant and wild type infections will be assessed by microscopy, molecular methods, parasite culture and mosquito feeding assays. Parasite clearance will be determined in the first days (d0-3) after treatment. The study population will consist of passively recruited patients with uncomplicated P. falciparum malaria and asymptomatically infected individuals who are microscopy positive for gametocytes. Participants will be treated with conventional therapies for uncomplicated malaria without randomization: artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA-PPQ). All doses are supervised. Parasite clearance is assessed ex vivo by ring-stage survival assays and by daily slides during the first days of treatment. Gametocyte carriage and gametocyte commitment/production will be determined for resistant and wild type infections before, during and after treatment. In addition, venous blood will be collected at three timepoints to assess transmission to mosquitoes before (d0), during (d2) and after treatment (d7). The total duration of participation will be 7 days, the primary endpoint will be the reduction in mosquito infection rates at d2 (artemether-lumefantrine) or d7 (dihydroartemisinin-piperaquine) compared to pre-treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started May 2024
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 29, 2024
CompletedFirst Posted
Study publicly available on registry
April 4, 2024
CompletedStudy Start
First participant enrolled
May 28, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2026
CompletedMarch 10, 2025
March 1, 2024
1.5 years
March 29, 2024
March 6, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Mean within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline.
Mean within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the AL and day 7 post-treatment in the DHA-PPQ arm. Infectivity is assessed by mosquito membrane feeding assays; percent reduction is calculated separately for ΔPfK13 vs wild type infections.
day 2 vs day 0 (AL arm) and day 7 vs day 0 (DP arm)
Secondary Outcomes (12)
Mean within person percent change (presented as percent reduction) in mosquito infection rate from baseline
days 0, 2, 7
Mean oocyst intensity (in all/all infected mosquitoes)
days 0, 2, 7
Male and female gametocyte sex ratio (proportion male)
days 0, 1, 2, 3, 7
Gametocyte circulation time
days 0, 1, 2, 3, 7
Gametocyte area under the curve
days 0, 1, 2, 3, 7
- +7 more secondary outcomes
Study Arms (2)
artemether-lumefantrine
ACTIVE COMPARATORartemether-lumefantrine according to manufacturer instructions
dihydroartemisinin-piperaquine
EXPERIMENTALdihydroartemisinin-piperaquine according to manufacturer instructions
Interventions
Participants in the Artemether-Lumefantrine arm will be treated with standard doses of AL (Coartem, Novartis). Tablets containing 20/80 mg artemether and 120/480 mg lumefantrine will be administered per manufacturer guidelines. All doses will be given under direct supervision with fatty food.
Participants in the DHA-PPQ arm will be treated with standard doses of DHA-PPQ. Tablets containing 40 mg dihydroartemisinin/320 mg piperaquine tablets (Eurartesim, Sigma Tau or Duocotecxin, Beijing Holley-Cotect Pharmaceutical Co) will be administered per manufacturer guidelines. All doses will be given under direct supervision on an empty stomach, as per manufacturer instructions.
Eligibility Criteria
You may qualify if:
- age ≥2 years
- blood smear positive for P. falciparum gametocytes
- mono-infection with P. falciparum confirmed by positive blood smear;
- parasitaemia of \>100 P. falciparum asexual forms/µL;
- 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;
- informed consent from parent or guardian;
- haemoglobin ≥ 7.0 g/dl for children below 10 years of age or ≥8.0g/dL for older individuals
You may not qualify if:
- presence of general danger signs;
- mixed or mono-infection with another Plasmodium species detected by microscopy;
- presence of severe malnutrition defined as a very low weight for height (below -3z scores of the median WHO growth standards), by visible severe wasting, or by the presence of nutritional oedema.
- 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);
- history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Dr. Ambrosoli Memorial Hospital
Kalongo, Agago district, Uganda
Patongo Health Facility IV
Patongo, Agago district, Uganda
Related Publications (2)
Conrad MD, Asua V, Garg S, Giesbrecht D, Niare K, Smith S, Namuganga JF, Katairo T, Legac J, Crudale RM, Tumwebaze PK, Nsobya SL, Cooper RA, Kamya MR, Dorsey G, Bailey JA, Rosenthal PJ. Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda. N Engl J Med. 2023 Aug 24;389(8):722-732. doi: 10.1056/NEJMoa2211803.
PMID: 37611122BACKGROUNDTumwebaze PK, Conrad MD, Okitwi M, Orena S, Byaruhanga O, Katairo T, Legac J, Garg S, Giesbrecht D, Smith SR, Ceja FG, Nsobya SL, Bailey JA, Cooper RA, Rosenthal PJ. Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda. Nat Commun. 2022 Oct 26;13(1):6353. doi: 10.1038/s41467-022-33873-x.
PMID: 36289202BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Teun Bousema, PhD
London School of Hygiene and Tropical Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 29, 2024
First Posted
April 4, 2024
Study Start
May 28, 2024
Primary Completion
December 1, 2025
Study Completion
April 1, 2026
Last Updated
March 10, 2025
Record last verified: 2024-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Upon publication
Anonymized data will be shared through an online repository