Back to resultsEvaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function
Primary Purpose
Malaria, Falciparum
Status
Completed
Phase
Phase 4
Locations
Colombia
Study Type
Interventional
Intervention
Artesunate-mefloquine
Atovaquone-proguanil
Artemether-lumefantrine
Sponsored by
About this trial
This is an interventional treatment trial for Malaria focused on measuring Malaria, hearing, co-artemether, auditory, Plasmodium falciparum, marsh fever, Plasmodium infections, remittent fever, paludism, artemether, artemisinins, benflumetol, lumefantrine
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Artemether-lumefantrine (Coartem)
Atovaquone-proguanil (Malarone)
Artesunate-mefloquine
Arm Description
Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days, dosage dependent on body weight.
Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days, dosage dependent on body weight.
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.
Outcomes
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)
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)
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00444106
Brief Title
Evaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
May 2007 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis
4. Oversight
5. Study Description
Brief Summary
To evaluate the potential effects of artemether- lumefantrine on the auditory function
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Falciparum
Keywords
Malaria, hearing, co-artemether, auditory, Plasmodium falciparum, marsh fever, Plasmodium infections, remittent fever, paludism, artemether, artemisinins, benflumetol, lumefantrine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
265 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Artemether-lumefantrine (Coartem)
Arm Type
Experimental
Arm Description
Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days, dosage dependent on body weight.
Arm Title
Atovaquone-proguanil (Malarone)
Arm Type
Active Comparator
Arm Description
Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days, dosage dependent on body weight.
Arm Title
Artesunate-mefloquine
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Artesunate-mefloquine
Other Intervention Name(s)
Plasmotrim, Mephaquin
Intervention Type
Drug
Intervention Name(s)
Atovaquone-proguanil
Other Intervention Name(s)
Malarone
Intervention Type
Drug
Intervention Name(s)
Artemether-lumefantrine
Other Intervention Name(s)
Coartem
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
7 days
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Baseline (Day 1), 3, 7, 28 and Day 42
Title
Relationship Between Changes in Auditory Function and Treatment Groups
Description
ABR Wave III latency (ms) changes from baseline to Day 7 in the three drug exposure groups.
Time Frame
From Baseline to Day 7
Title
Efficacy of Polymerase Chain Reaction (PCR) Adjusted Malaria Cure Rates of the Three Treatment Regimens at Days 14, 28 and 42
Description
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.
Time Frame
Days 14, 28 and 42
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis
Organizational Affiliation
Novartis
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigational Site
City
Tumaco
Country
Colombia
12. IPD Sharing Statement
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Evaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function
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