MalariaPhase 4NCT00444106
Evaluation of Potential Effect of Artemether - Lumefantrine and Malaria Drugs on Auditory Function
A Phase 4 study testing Artesunate-mefloquine, Atovaquone-proguanil and Artemether-lumefantrine in people with Malaria and Falciparum, run by Novartis at 1 site in Colombia.
Trial summary
To evaluate the potential effects of artemether- lumefantrine on the auditory function Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Malaria, Falciparum
- What is being tested?
- Artesunate-mefloquine, Atovaquone-proguanil and Artemether-lumefantrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 1 siteColombia
- Study dates
- May 2007to Nov 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
To evaluate the potential effects of artemether- lumefantrine on the auditory function
- Conditions
- Malaria, Falciparum
- Being tested
- Artesunate-mefloquine, Atovaquone-proguanil, Artemether-lumefantrine
- Keywords
- Malaria, hearing, co-artemether, auditory, Plasmodium falciparum, marsh fever, Plasmodium infections, remittent fever, paludism, artemether, artemisinins, benflumetol, lumefantrine
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artesunate-mefloquineDrug
Also called Plasmotrim, Mephaquin
Atovaquone-proguanilDrug
Also called Malarone
Artemether-lumefantrineDrug
Also called Coartem
| Study group | Role | What they receive |
|---|---|---|
| Artemether-lumefantrine (Coartem) | Experimental | Artemether-lumefantrine (Coartem) tablets containing 20 mg artemether and 120 mg lumefantrine twice a day for 3 days, dosage dependent on body weight. Receives: Drug: Artemether-lumefantrine |
| Atovaquone-proguanil (Malarone) | Active comparator | Atovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days, dosage dependent on body weight. Receives: Drug: Atovaquone-proguanil |
| Artesunate-mefloquine | Active comparator | 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. Receives: Drug: Artesunate-mefloquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days
Secondary outcomes (3)
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.
Measured: Baseline (Day 1), 3, 7, 28 and Day 42
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.
Measured: From Baseline to Day 7
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.
Measured: Days 14, 28 and 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2007 (estimated)
- Study startMay 2007
- Primary completionNov 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 265 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Novartis, Study director, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00444106
- Sponsor's protocol ID
- CCOA566A2417
- Status last verified
- Apr 2011
- First submitted
- 6 Mar 2007
- Last updated
- 5 Apr 2011
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00444106
- Acronym / sponsor ID
- CCOA566A2417
- Conditions
- Malaria, Falciparum
- Keywords
- Malaria, hearing, co-artemether, auditory, Plasmodium falciparum, marsh fever, Plasmodium infections, remittent fever
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 265 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 7 Mar 2007 (estimated)
- Results
- Posted 16 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the potential effects of artemether- lumefantrine on the auditory function
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Artemether-lumefantrine (Coartem) | Experimental | Drug: Artemether-lumefantrineArtemether-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) | Active comparator | Drug: Atovaquone-proguanilAtovaquone-proguanil (Malarone) tablets containing 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for 3 days, dosage dependent on body weight. |
| Artesunate-mefloquine | Active comparator | Drug: Artesunate-mefloquineArtesunate-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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Artesunate-mefloquineAlso: Plasmotrim, Mephaquin | Drug | Artesunate-mefloquine |
| Atovaquone-proguanilAlso: Malarone | Drug | Atovaquone-proguanil (Malarone) |
| Artemether-lumefantrineAlso: Coartem | Drug | Artemether-lumefantrine (Coartem) |
Primary outcome
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.
3 secondary outcomes
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
Relationship Between Changes in Auditory Function and Treatment Groups
Time frame: From Baseline to Day 7
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis study director
Novartis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Artesunate-mefloquine, Atovaquone-proguanil and Artemether-lumefantrine in people with Malaria and Falciparum, run by Novartis at 1 site in Colombia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2011.