Efficacy of Artesunate + Amodiaquine Versus Artemether-lumefantrine for Falciparum Malaria in Zanzibar, 2005

NCT03768908 | Completed Phase 4

• 1 other identifier: ACO II
• Study Type: interventional
• Target: 359
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of the study was to determine the PCR-APCR up to day 42 in children \<60 months of age, weighing ≥5kg with uncomplicated malaria, treated with either artesunate+ amodiaquine (ASAQ) or artemether-lumefantrine (AL; Coartem®). Secondary objectives included: clinical and laboratory assessment of drug tolerability and safety, evaluation of possible correlation between drug bioavailability and clinical outcome, comparison of efficacy data with the pre-implementation "ACO I" study, parasite and fever clearance, gametocyte carriage, and possible selection of mutations related to quinoline resistance.

Conditions

Plasmodium Falciparum Malaria

Keywords

Artemether-Lumefantrine; Coartem; Artesunate; Amodiaquine; Zanzibar

Outcome Measures

Primary Outcomes (1)

• PCR adjusted parasitological cure rates by day 42

  Comparing PCR adjusted parasitological cure rate (PCR-APCR) between the two treatment options up to day 42. Parasitological cure will be adjusted using PCR genotyping of msp2 marker. Recrudescence is defined as the presence of at least one matching allelic band, and reinfection as the absence of any matching allelic band on day 0 and day of recurring parasitaemia. Patients with recurrent parasitaemia having missing filter paper sample or negative PCR results will be considered uncertain with regards to PCR adjusted outcome.

  42 days

Secondary Outcomes (1)

• The clinical and parasitological response outcome (i.e. cure rates) on days 14, day 28 and 42.

  42 days

Other Outcomes (4)

• Clinical and laboratory assessment of drug tolerability and safety i.e., incidence of adverse events.

  42 days

• Fever clearance in the two study arms

  42 days

• Parasite clearance and gametocyte carriage in the two study arms

  42 days

Study Arms (2)

Treatment with artesunate + amodiaquine

ACTIVE COMPARATOR

Co-administration of a daily dose of artesunate (Arsumax) 4mg/kg and amodiaquine (Flavoquine) 10mg/kg for 3 days, under direct observation. Children \<12months \<10kg: artesunate (Arsumax) 50mg - 0.5tab/day + amodiaquine (Flavoquine) 153mg - 0.5tab/day; Children 12-59months 10-20kg: artesunate (Arsumax) 50mg - 1 tab/day + amodiaquine (Flavoquine) 153mg 1 tab/day.

Drug: Artesunate + Amodiaquine

Treatment with artemether-lumefantrine (Coartem®)

ACTIVE COMPARATOR

Artemether-lumefantrine (Coartem®) - artemether 1.3mg/kg + lumefantrine 4mg/kg administered twice daily, both doses under direct observation either in the clinic or in the patient's home. Children \<60 months, 5-14kg: 1 tab/dose; Children \<60 months \>14kg: 2 tabs/dose.

Drug: Artemether-lumefantrine

Interventions

Artemether-lumefantrine DRUG

Three day treatment with Artemether-lumefantrine, 2 doses a day under direct observation

Also known as: Coartem®

Treatment with artemether-lumefantrine (Coartem®)

Artesunate + Amodiaquine DRUG

Three day treatment with Artesunate + Amodiaquine, co-administered, a dose a day under direct observation

Also known as: ASAQ

Treatment with artesunate + amodiaquine

Eligibility Criteria

• Age: Up to 60 Months
• Sex: all
• Age Groups: Child (0-17)

You may qualify if:

• Weight ≥5kg
• No general danger signs or severe malaria present (see 4.4.2.1 \& 4.4.2.2)
• History of fever within 24 hours OR axillary temperature ≥ 37.5Cº
• No other cause of fever is detectable
• No severe malnutrition
• Patient has parasite counts between 2000-200,000/ul (50-5000/200 white blood cells)
• Guardian/Patient has understood the procedures of the study and is willing to participate
• Patient able to come for stipulated follow up visits and has easy access to the Study Site

You may not qualify if:

• General Danger Signs and Complications:
• Not able to drink or breastfeed
• Vomiting everything
• Recent history of convulsions
• Lethargic or unconscious
• Unable to sit or stand (as appropriate for age)
• History of allergy to test drugs
• History of intake of any drugs other than paracetamol and aspirin within 3 days
• Signs of Severe Malaria:
• Altered consciousness
• Repeated convulsions
• Inability of oral intake
• Severe anaemia (Hb \<5gm/dl)
• Difficulty in breathing (pulmonary oedema, Respiratory Distress Syndrome)
• Shock (small pulse, cold extremities)

Sponsors & Collaborators

• Professor Anders Björkman: lead
• Zanzibar Malaria Control Programme: collaborator

Related Publications (1)

• Holmgren G, Hamrin J, Svard J, Martensson A, Gil JP, Bjorkman A. Selection of pfmdr1 mutations after amodiaquine monotherapy and amodiaquine plus artemisinin combination therapy in East Africa. Infect Genet Evol. 2007 Sep;7(5):562-9. doi: 10.1016/j.meegid.2007.03.005. Epub 2007 Mar 31.

  PMID: 17467344 BACKGROUND

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination; amodiaquine, artesunate drug combination

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Johan Stromberg

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Mwinyi I Msellem

  Zanzibar Malaria Control Programme

• Andreas Martensson

  Karolinska Institutet

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No blinding was done due to the different drug formulations and regimens.
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: A multicentre randomised comparative clinical trial of the efficacy of ASAQ versus AL for the treatment of uncomplicated childhood Plasmodium falciparum malaria.

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 7, 2018
• Study Start: January 5, 2005
• Primary Completion: July 11, 2005
• Study Completion: July 11, 2005
• Last Updated: December 7, 2018

Record last verified: 2018-12