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

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ClinicalTrials.gov Identifier: NCT03768908
Recruitment Status : Completed
First Posted : December 7, 2018
Last Update Posted : December 7, 2018
Sponsor:
Collaborator:
Zanzibar Malaria Control Programme
Information provided by (Responsible Party):
Professor Anders Björkman, Karolinska Institutet

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.


Condition or disease Intervention/treatment Phase
Plasmodium Falciparum Malaria Drug: Artemether-lumefantrine Drug: Artesunate + Amodiaquine Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 359 participants
Allocation: Randomized
Intervention Model Description: A multicentre randomised comparative clinical trial of the efficacy of ASAQ versus AL for the treatment of uncomplicated childhood Plasmodium falciparum malaria.
Masking: None (Open Label)
Masking Description: No blinding was done due to the different drug formulations and regimens.
Primary Purpose: Treatment
Official Title: A Multicentre Randomised Comparative Clinical Trial of the Efficacy of Artesunate + Amodiaquine Versus Artemether-lumefantrine (Coartem®) for the Treatment of Uncomplicated Childhood Plasmodium Falciparum Malaria in Zanzibar
Actual Study Start Date : January 5, 2005
Actual Primary Completion Date : July 11, 2005
Actual Study Completion Date : July 11, 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Active Comparator: Treatment with artesunate + amodiaquine
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
Three day treatment with Artesunate + Amodiaquine, co-administered, a dose a day under direct observation
Other Name: ASAQ

Active Comparator: Treatment with artemether-lumefantrine (Coartem®)
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
Three day treatment with Artemether-lumefantrine, 2 doses a day under direct observation
Other Name: Coartem®




Primary Outcome Measures :
  1. PCR adjusted parasitological cure rates by day 42 [ Time Frame: 42 days ]
    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.


Secondary Outcome Measures :
  1. The clinical and parasitological response outcome (i.e. cure rates) on days 14, day 28 and 42. [ Time Frame: 42 days ]
    Comparing proportion of response outcomes according to standard WHO classification i.e., cure rates on days 14, day 28 and 42. Defined as the absence of both re-parasitaemia and clinical symptoms suggestive of severe malaria during follow-up to the respective days.


Other Outcome Measures:
  1. Clinical and laboratory assessment of drug tolerability and safety i.e., incidence of adverse events. [ Time Frame: 42 days ]
    Proportion of patients reporting any adverse event (AE) in the two study arms. The intensity of an adverse event was determined according to the following definitions: mild, moderate, severe, unknown. AEs were be categorized according to if there is a likely causal relationship between the event and the medical products: probably, possibly, unlikely.

  2. Fever clearance in the two study arms [ Time Frame: 42 days ]
    Fever clearance was determined by a medical doctor/officer who measured the patient's axillary temperature using an electronic thermometer and took a detailed clinical history as well as performed a clinical examination. All details were recorded in the CRF.

  3. Parasite clearance and gametocyte carriage in the two study arms [ Time Frame: 42 days ]
    Clearance of parasites and gametocyte carriage were determined by Giemsa stained thick blood films were examined using electrical or sunlight microscope at the study site by an experienced microscopist. The number of parasites were calculated as the number of parasites seen against 200 leucocytes in the thick blood film and recorded in the CRF for the correct occasion. The slides were stored for quality controls, 10% of all slides were double-checked centrally.

  4. Proportion of mutations related to Quinoline resistance at day0 and day of recurrent infection in the two study arms [ Time Frame: 42 days ]
    Proportions of single nucleotide polymorphisms at pfmdr1 Y86N and pfcrt K76T determined by established AluI restriction-based PCR-RFLP.



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Ages Eligible for Study:   up to 60 Months   (Child)
Sexes Eligible for Study:   All
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

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)
  • Hypoglycaemia
  • Haemoglobinuria (dark coloured urine or Coca-Cola urine)
  • Kidney failure (little or no urine in a well-hydrated patient)
  • Jaundice (yellow colouring of eyes)
  • Hyperpyrexia (temperature above 39.5ºC) in combination with other signs
  • Hyperparasitaemia (more than 5% red blood cells parasitized or >200,000 parasites/µl)
  • Spontaneous bleeding (Disseminated Intravascular Coagulation)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03768908


Sponsors and Collaborators
Professor Anders Björkman
Zanzibar Malaria Control Programme
Investigators
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Principal Investigator: Johan Stromberg Karolinska Institutet
OverallOfficial: Mwinyi I Msellem Zanzibar Malaria Control Programme
OverallOfficial: Andreas Martensson Karolinska Institutet

Publications:
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Responsible Party: Professor Anders Björkman, Professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03768908     History of Changes
Other Study ID Numbers: ACO II
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018

Keywords provided by Professor Anders Björkman, Karolinska Institutet:
Artemether-Lumefantrine
Coartem
Artesunate
Amodiaquine
Zanzibar

Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Artesunate
Lumefantrine
Artemether
Artemether, Lumefantrine Drug Combination
Amodiaquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics