Clinical trial NCT01258049: Superiority of ArTiMist Versus Quinine in Children With Severe Malaria
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Plasmodium Falciparum Malaria
Keywords: Plasmodium infections
Remittent fever
Artemether
Artemesinins
Quinine
Malaria
Protozoan infections
sublingual drug delivery
Parasitic disease
Antiprotozoan agents
Lead sponsor: Proto Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2010-12-10
Enrollment: 151
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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.

Eligibility criteria: Inclusion Criteria:

1. The patient's legally acceptable representative has provided informed consent and the patient has assented (where relevant) to participation in the trial
2. The patient is a child that weighs between 5.00 kg and 15.00 kg inclusive
3. 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)
4. 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.

Exclusion Criteria:

1. 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.
2. Ability to tolerate oral therapy
3. Patient has received any antimalarial therapy within the 7 days prior to first study drug administration.
4. Patient has evidence of significant co-infections (this does not include mixed Plasmodium infections).
5. Patient has a contraindication, allergy or is otherwise intolerant to either artemether or quinine .

Primary outcomes:
measure: Parasitological Success (MITT)
timeFrame: 24 hours after start of treatment
measure: Parasitological Success (PP)
timeFrame: 24 hours after start of treatment
Secondary outcomes:
measure: Parasite Clearance Time (PCT) [MITT Population]
timeFrame: 28 days after start of treatment
measure: PCT 90 [MITT Population]
timeFrame: 28 days after start of treatment
measure: PCT 50 [MITT Population]
timeFrame: 28 days after start of treatment
measure: PRR 24 [MITT Population]
timeFrame: 28 days after start of treatment
measure: PRR 12 [MITT Population]
timeFrame: 28 days after start of treatment
measure: Fever Clearance Time (FCT)
timeFrame: 28 days after start of treatment
measure: Complete Cure Rate
timeFrame: 28 days after the start of treatment
measure: Early Treatment Failure
timeFrame: Three days after the start of treatment
measure: Late Clinical Failure
timeFrame: 28 days after the start of treatment
measure: Late Parasitological Failure
timeFrame: 28 days after the start of treatment
measure: Time to Return to Full Consciousness
timeFrame: 28 days after start of treatment
measure: Time to Return to Normal Per os Status
timeFrame: 28 days after start of treatment
measure: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events, of Possible, Probably and Definite Causalities
timeFrame: 28 days after start of treatment
measure: Number of Deaths or Neurological Sequelae at Day 28
timeFrame: 28 days after start of treatment
Other outcomes:
Locations:
city: Ouagadougou
country: Burkina Faso
facility: Centre National de Recherche et de Formation sur le Paludisme (CNRFP)
city: Navrongo
country: Ghana
facility: Navrongo Health Research Centre
city: Rwinkwavu
country: Rwanda
facility: Rwinkwavu District Hospital
state: Eastern Province
Study officials:
affiliation: Xidea Solutions Limited
name: Daryl Bendel, MBChB MFPM
role: STUDY_CHAIR
References:
citation: 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.