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Evaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function

This study has been completed.
Information provided by:
Novartis Identifier:
First received: March 6, 2007
Last updated: April 1, 2011
Last verified: April 2011
To evaluate the potential effects of artemether- lumefantrine on the auditory function

Condition Intervention Phase
Malaria Falciparum Drug: Artesunate-mefloquine Drug: Atovaquone-proguanil Drug: Artemether-lumefantrine Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Single-center, Parallel Group Study of the Effects of Artemether-lumefantrine (Coartem®) Atovaquone-proguanil (Malarone®) and Artesunate-mefloquine on Auditory Function Following the Treatment of Acute Uncomplicated Plasmodium Falciparum Malaria in Patients 12 Years of Age or Older

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants With Auditory Abnormalities at Day 7 Assessed by Auditory Brainstem Response (ABR) Wave III Latency Changes on Day 7(a Type of Hearing Test) [ Time Frame: 7 days ]
    To demonstrate the safety of artemether-lumefantrine after 3 days of treatment in patients with acute, uncomplicated falciparum malaria by testing the null hypothesis that the rate of auditory abnormalities is ≥ 15% in the population treated with artemether-lumefantrine as assessed by ABR at Day 7 following initiation of treatment compared with their baseline values. An "auditory nerve abnormality" is here defined as a greater than 0.30 ms change in Wave III latency from baseline to Day 7. Exact Pearson-Clopper two-sided 95% confidence limits were constructed for all three treatment groups.

Secondary Outcome Measures:
  • Auditory Changes Following 3 Days of Treatment at Days 3, 7, 28, and 42 Days as Assessed by Pure Tone Thresholds Assessments (a Type of Hearing Test) [ Time Frame: Baseline (Day 1), 3, 7, 28 and Day 42 ]
    Audiometric measurements such as pure-tone threshold (air conduction tested at 250 to 8000 HZ) day 3, 7, 28 and 42 following initiation of treatment, including changes from baseline. Pure-tone average (PTA) calculated for each ear by averaging the pure-tone threshold values at 500, 1000, 2000 and 3000 HZ.

  • Relationship Between Changes in Auditory Function and Treatment Groups [ Time Frame: From Baseline to Day 7 ]
    ABR Wave III latency (ms) changes from baseline to Day 7 in the three drug exposure groups.

  • Efficacy of Polymerase Chain Reaction (PCR) Adjusted Malaria Cure Rates of the Three Treatment Regimens at Days 14, 28 and 42 [ Time Frame: Days 14, 28 and 42 ]
    Percentage of patients with clearance of asexual parasitemia (observed by optical microscopy) within 7 days of initiation of trial treatment without recrudescence within 14, 28 and 42 days respectively after initiation of treatment. Patients with recurrent parasitemia and paired PCR results were classified as either a new infection (different paired genotypes) or a recrudescence (matching paired genotypes). Patients without paired PCR results or ambiguous results were classified as treatment failures.

Enrollment: 265
Study Start Date: May 2007
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Artemether-lumefantrine (Coartem)
Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days, dosage dependent on body weight.
Drug: Artemether-lumefantrine
Other Name: Coartem
Active Comparator: Atovaquone-proguanil (Malarone)
Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days, dosage dependent on body weight.
Drug: Atovaquone-proguanil
Other Name: Malarone
Active Comparator: Artesunate-mefloquine
Artesunate-mefloquine tablets containing 50 mg artesunate (Plasmotrim) and 250 mg mefloquine (Mephaquin). Artesunate 4 mg/kg/day (for 3 days) and mefloquine 25 mg/kg/day (days 2 and 3) total dose was given once daily dependent upon body weight.
Drug: Artesunate-mefloquine
Other Names:
  • Plasmotrim
  • Mephaquin


Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All

Inclusion Criteria

  • 12 years of age or older
  • Accepts Healthy Volunteers
  • P. falciparum parasitemia between 1,000 and 100,000 parasites/μl
  • History of fever or presence of fever (temperature ≥ 37.5°C)

Exclusion Criteria

  • Signs/symptoms of severe/complicated malaria
  • Ingestion of various antimalarial drugs, or antibiotics in the previous 2 weeks to 2 months
  • History of any drug-related hearing impairment
  • Abnormal hearing function at study entry
  • Exposure to sustained loud noises, by self-report, within the past 24 hours
  • Present ear problems
  • Pregnant or lactating (urine test for β-HCG) to be performed on any woman of child bearing age)

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
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Please refer to this study by its identifier: NCT00444106

Novartis Investigational Site
Tumaco, Colombia
Sponsors and Collaborators
Study Director: Novartis Novartis
  More Information

Responsible Party: Novartis Identifier: NCT00444106     History of Changes
Other Study ID Numbers: CCOA566A2417
Study First Received: March 6, 2007
Results First Received: December 8, 2010
Last Updated: April 1, 2011

Keywords provided by Novartis:
Plasmodium falciparum
marsh fever
Plasmodium infections
remittent fever

Additional relevant MeSH terms:
Protozoan Infections
Parasitic Diseases
Atovaquone, proguanil drug combination
Artemether-lumefantrine combination
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antifungal Agents
Antiplatyhelmintic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites processed this record on June 23, 2017