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Plasmodium Falciparum MalariaPhase 3NCT01258049

Superiority of ArTiMist Versus Quinine in Children With Severe Malaria

A Phase 3 study testing Artemether Sublingual Spray and Quinine in people with Plasmodium Falciparum Malaria, run by Proto Pharma Ltd at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to demonstrate that ArTiMist (sublingual artemether spray) is better than intravenous quinine in reducing parasite counts by >= 90% within 24 hours after the start of treatment in children with severe malaria, or uncomplicated malaria with gastrointestinal complications Read more about this study

Who is it for?
Any age
Conditions the study is for
Plasmodium Falciparum Malaria
What is being tested?
Artemether Sublingual Spray and Quinine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
151 participants
Where
3 sitesin 3 countries
Study dates
Dec 2010to Sep 2012
Phase
Phase 3
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • The patient's legally acceptable representative has provided informed consent and the patient has assented (where relevant) to participation in the trial
  • The patient is a child that weighs between 5.00 kg and 15.00 kg inclusive
  • The patient has falciparum malaria as evidenced by thick or thin blood smears of ≥ 500 P Falciparum per mcl (patients with mixed infections may be included provided ≥ 500 P Falciparum per mcl)
  • The patient has either:
  • severe or complicated falciparum malaria as determined by the investigator based on the WHO criteria for severity, and/or
  • uncomplicated falciparum malaria but is unable to tolerate oral medication as a result of gastrointestinal complications such as vomiting or diarrhoea.

Who cannot join

  • The patient's legally acceptable representative does not provide informed consent for participation, or the child if capable, does not assent to participation in the trial.
  • Ability to tolerate oral therapy
  • Patient has received any antimalarial therapy within the 7 days prior to first study drug administration.
  • Patient has evidence of significant co-infections (this does not include mixed Plasmodium infections).
  • Patient has a contraindication, allergy or is otherwise intolerant to either artemether or quinine .

Trial locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

Burkina Faso1 site

  • Centre National de Recherche et de Formation sur le Paludisme (CNRFP)

    Ouagadougou, 01 BP 2208

Other trials in Burkina Faso

Ghana1 site

  • Navrongo Health Research Centre

    Navrongo, Navrongo, P.O. Box 114

Other trials in Ghana

Rwanda1 site

  • Rwinkwavu District Hospital

    Rwinkwavu, Eastern Province

Other trials in Rwanda

About this study

Official title: A Phase III, Randomised, Open Labelled, Active Controlled, Multi Centre, Superiority Trial of ArTiMist™ Versus Intravenous Quinine in Children With Severe or Complicated Falciparum Malaria, or Uncomplicated Falciparum Malaria With Gastrointestinal Complications.

The purpose of this study is to demonstrate that ArTiMist (sublingual artemether spray) is better than intravenous quinine in reducing parasite counts by >= 90% within 24 hours after the start of treatment in children with severe malaria, or uncomplicated malaria with gastrointestinal complications

Read the detailed description

Malaria causes significant morbidity and mortality in children in developing countries, despite the availability of highly effective antimalarial therapy. One of the key contributing factors is the delay in the initiation of treatment.

ArTiMist is a sublingual formulation of the established antimalarial treatment, artemether. In previous studies good bioavailability has been demonstrated. In an exploratory study (ART003) ArTiMist demonstrated a non statistically significant improvement of 26% (when compared to intravenous quinine) in the numbers of patients experiencing a parasite reduction of >= 90% within 24 hours of the initiation of treatment.

This Phase 3 study is being conducted to establish whether treatment with ArTiMist in children with severe falciparum malaria or uncomplicated falciparum malaria with gastrointestinal complications is at least 20% superior in providing parasitological success (defined as >= 90% reduction in parasite count at 24 hours after start of treatment) when compared to intravenous quinine.

Being tested
Artemether Sublingual Spray, Quinine
Keywords
Plasmodium infections, Remittent fever, Artemether, Artemesinins, Quinine, Malaria, Protozoan infections, sublingual drug delivery, Parasitic disease, Antiprotozoan agents
Medical subject headings
Malaria, Falciparum, Malaria, Protozoan Infections, Parasitic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Artemether Sublingual SprayDrug

    Also called ArTiMist

    Artemether sublingual spray administered at 3 mg/kg (milligrams per kilogram) at specified timepoints

  • QuinineDrug

    Quinine administered intravenously, 20 mg/kg loading dose followed by 10 mg/kg every eight hours

Study groups in NCT01258049
Study groupRoleWhat they receive
ArTiMistExperimentalNot described
Receives: Drug: Artemether Sublingual Spray
QuinineActive comparatorNot described
Receives: Drug: Quinine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Parasitological Success (MITT)

    Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose

    Measured: 24 hours after start of treatment

  2. Parasitological Success (PP)

    Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose

    Measured: 24 hours after start of treatment

Secondary outcomes (14)

  1. Parasite Clearance Time (PCT) [MITT Population]

    Parasite clearance time (PCT). Time in hours from the initiation of therapy until the first of two successive parasite negative smears (zero parasite counts) are obtained

    Measured: 28 days after start of treatment

  2. PCT 90 [MITT Population]

    Time for parasite counts to fall by 90%

    Measured: 28 days after start of treatment

  3. PCT 50 [MITT Population]

    Time for parasite counts to fall by 50%

    Measured: 28 days after start of treatment

  4. PRR 24 [MITT Population]

    The percentage reduction in parasite counts 24 hours after first dose

    Measured: 28 days after start of treatment

  5. PRR 12 [MITT Population]

    The percentage reduction in parasite counts 12 hours after first dose

    Measured: 28 days after start of treatment

  6. Fever Clearance Time (FCT)

    Time in hours from the initiation of therapy until the disappearance of fever (tympanic temperature < 38.0) that lasted at least 24 hours.

    Measured: 28 days after start of treatment

  7. Complete Cure Rate

    The complete resolution of clinical signs and symptoms, malaria-related laboratory abnormalities, and elimination of asexual parasites by Day 7, with no recurrence up to Day 28 (+/- 2 days), and the 48h parasite count to be < 25% of baseline with no clinical deterioration

    Measured: 28 days after the start of treatment

  8. Early Treatment Failure

    Early treatment failure is indicated by one or more of the following:

    • Parasite count on Day 2 > Day 0, irrespective of temperature
    • Parasite count on Day 3 > 0 with tympanic temperature ≥ 38.0°C
    • Parasite count on Day 3 ≥ 25% of baseline
    • Administration of rescue antimalarial treatment

    Measured: Three days after the start of treatment

  9. Late Clinical Failure

    • Signs of severe malaria on any day between Day 4 and Day 28 in the presence of parasitaemia, without previously meeting any of the criteria of early treatment failure
    • Presence of parasitaemia and tympanic temperature ≥ 38.0°C (or history of fever), on any day between Day 4 and Day 28, without previously meeting any of the criteria of early treatment failure

    Measured: 28 days after the start of treatment

  10. Late Parasitological Failure

    • Parasitaemia on any day from Day 7 to Day 28 and tympanic temperature ≤ 38.0°C

    Measured: 28 days after the start of treatment

  11. Time to Return to Full Consciousness

    Time in hours to return to full consciousness (Blantyre Coma Scale = 5), if level of consciousness is reduced (Blantyre Coma Scale <5) prior to dosing or within 24hours of first dosing.

    For the Blantyre Coma Scale

    Total - maximum 5, eye movement - maximum 1, best motor response - maximum 2, best verbal response - maximum 2

    Measured: 28 days after start of treatment

  12. Time to Return to Normal Per os Status

    Time in hours to return to normal per os status. Normal per os was when the investigator considered the patient to be able to eat and drink normally.

    Measured: 28 days after start of treatment

  13. Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events, of Possible, Probably and Definite Causalities

    Measured: 28 days after start of treatment

  14. Number of Deaths or Neurological Sequelae at Day 28

    Measured: 28 days after start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Dec 2010 (estimated)
  2. Study startDec 2010
  3. Primary completionAug 2012
  4. Study completionSep 2012

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01258049
Sponsor's protocol ID
ART004
Status last verified
Jan 2014
First submitted
9 Dec 2010
Last updated
28 Feb 2014
Data monitoring committee
Yes

Publications

  • Bendel D, Rulisa S, Ansah P, Sirima S. Efficacy of a novel sublingual spray formulation of artemether in African children with Plasmodium falciparum malaria. Antimicrob Agents Chemother. 2015 Nov;59(11):6930-8. doi: 10.1128/AAC.00243-15. Epub 2015 Aug 24.

    PubMed 26303805

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Artemether Sublingual Spray and Quinine in people with Plasmodium Falciparum Malaria, run by Proto Pharma Ltd at 3 sites in 3 countries.

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 6 inclusion and 5 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 28 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Burkina Faso, Ghana, Rwanda. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 28 Feb 2014). 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?

Parasitological Success (MITT) (time frame: 24 hours after start of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01258049, which also lists 1 linked publication.

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 28 Feb 2014.

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