Efficacy of ArTiMist™ in Children

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of Artemether Sublingual Spray (ArTiMist™) with intravenous quinine in children with severe or complicated falciparum malaria, or children with uncomplicated malaria with gastrointestinal complications.

Official Title
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An Open Label Randomised Comparative Trial to Establish the Efficacy of 3 mg/kg ArTiMist™ When Compared to Intravenous Quinine in Children With Severe or Complicated Falciparum Malaria, or Uncomplicated Falciparum Malaria With Gastrointestinal Complications

Conditions
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Falciparum Malaria

Intervention / Treatment
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* Drug: Quinine
* Drug: Artemether


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient's parent or attendant relative 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 and 15 kg (kilogram) The patient has falciparum malaria as evidenced by Thick or thin blood smears of > 500 P falciparum per mcl (microlitre)(patients with mixed infections may be included provided >500 P Falciparum /mcl) and /or Positive RDT (rapid diagnostic test)for malaria The patient has either severe or complicated malaria as determined by the Investigator based on the WHO criteria for severity, or the patient has uncomplicated malaria but is unable to tolerate oral medication as a result of gastrointestinal complications such as vomiting or diarrhoea. Exclusion Criteria: Attending relative or parent 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 treatment with an artemisinin or quinine in the last 24 hours Patient has evidence of significant co-infections (this does not include mixed Plasmodium infections). Patient is allergic or intolerant to artemisinins.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ArTiMist (artemether sublingual spray)<br> | Drug: Artemether<br>* Artemether sublingual spray 3 mg/kg at protocol specified timepoints until resumption of normal oral therapy<br>* Other names: ArTiMist™;|
| Active Comparator: Intravenous Quinine<br> | Drug: Quinine<br>* 20 mg/kg intravenous quinine loading dose, followed by 10 mg/kg intravenously every 8 hours until resumption of normal oral therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasitological Success Defined as a Reduction in Parasite Count of ≥ 90% of Baseline at 24 Hours After the First Dose |  | 24 hours after first dose | 
| Time for Parasite Count to Fall by 90% PCT(90) | The time taken for the parasite count to fall 90% from baseline | 3h (hours), 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h | 
| Time for Parasite Count to Fall by 50% PCT(50) | The time taken for the parasite count to fall 50% from baseline | 3 h (hours) , 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite Clearance Time | Time in hours from the initiation of therapy until the first of two successive parasite-negative smears were obtained | 3h (hours), 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h | 
| Parasite Reduction Ratio (PRR) at 24 h (Hours) After the First Dose | Reduction in parasitaemia from baseline at 24 h after the first dose of study medication | 24 hours after first dose | 
| Parasite Reduction Ratio (PRR) at 12 Hours After the First Dose | Reduction in parasitaemia from baseline at 12 hours after the first dose of study medication | 12 h (hours) after first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmodium infections, Remittent fever, Artemether, Artemisinins, quinine, Malaria, Protozoan Infections, Anti-Infective Agents, Antiprotozoal Agents, Schistosomicides, Pharmacologic Actions, Malaria, Falciparum, Antimalarials, Antiparasitic Agents, Parasitic Diseases, sublingual