Falciparum MalariaPhase 2NCT01047436

Efficacy of ArTiMist™ in Children

A Phase 2 study testing Quinine and Artemether in people with Falciparum Malaria, run by Proto Pharma Ltd.

Completed

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

Trial summary

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. Read more about this study

Who is it for?: Any age
Conditions the study is for: Falciparum Malaria
What is being tested?: Quinine and Artemether
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: No sites listed yet
Study dates: Dec 2009to Jan 2010
Phase: Phase 2
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 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.

Who cannot join

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.

About this study

Official title: 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: Falciparum Malaria
Being tested: Quinine, Artemether
Keywords: 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
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.

QuinineDrug
20 mg/kg intravenous quinine loading dose, followed by 10 mg/kg intravenously every 8 hours until resumption of normal oral therapy
ArtemetherDrug
Also called ArTiMist™
Artemether sublingual spray 3 mg/kg at protocol specified timepoints until resumption of normal oral therapy

Study groups in NCT01047436
Study group	Role	What they receive
ArTiMist (artemether sublingual spray)	Experimental	Not described Receives: Drug: Artemether
Intravenous Quinine	Active comparator	Not described Receives: Drug: Quinine

What is being measured

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

Parasitological Success Defined as a Reduction in Parasite Count of ≥ 90% of Baseline at 24 Hours After the First Dose
Measured: 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
Measured: 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
Measured: 3 h (hours) , 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h

Secondary outcomes (3)

Parasite Clearance Time
Time in hours from the initiation of therapy until the first of two successive parasite-negative smears were obtained
Measured: 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
Measured: 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
Measured: 12 h (hours) after first dose

Timeline

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

Dec 2009Jan 2010

First posted12 Jan 2010 (estimated)
Study startDec 2009
Primary completionJan 2010
Study completionJan 2010

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Falciparum 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01047436
Sponsor's protocol ID: ART003
Status last verified: Jan 2011
First submitted: 8 Jan 2010
Last updated: 27 Jan 2011
Results posted: Yes, on ClinicalTrials.gov
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Not yet recruiting
Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
Malaria
Active, not recruitingPhase 4
Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics
Malaria,Falciparum, Malaria in Pregnancy
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
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All Falciparum Malaria trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01047436
Acronym / sponsor ID: ART003
Conditions: Falciparum Malaria
Keywords: Plasmodium infections, Remittent fever, Artemether, Artemisinins, quinine, Malaria, Protozoan Infections, Anti-Infective Agents
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: Proto Pharma LtdIndustry (pharma, biotech, devices)
Collaborators: Xidea Solutions Limited
Study start: Dec 2009
Primary completion: Jan 2010 (actual)
Study completion: Jan 2010 (actual)
First posted: 12 Jan 2010 (estimated)
Results: Posted 14 Jan 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
ArTiMist (artemether sublingual spray)	Experimental	Drug: Artemether
Intravenous Quinine	Active comparator	Drug: Quinine

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

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
The patient has either

Key exclusion criteria (5 listed)

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.

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
Quinine20 mg/kg intravenous quinine loading dose, followed by 10 mg/kg intravenously every 8 hours until resumption of normal oral therapy	Drug	Intravenous Quinine
ArtemetherAlso: ArTiMist™Artemether sublingual spray 3 mg/kg at protocol specified timepoints until resumption of normal oral therapy	Drug	ArTiMist (artemether sublingual spray)

Primary outcome

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

3 secondary outcomes

Parasite Clearance Time
Time frame: 3h (hours), 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h
Parasite Reduction Ratio (PRR) at 24 h (Hours) After the First Dose
Time frame: 24 hours after first dose
Parasite Reduction Ratio (PRR) at 12 Hours After the First Dose
Time frame: 12 h (hours) after first dose

Results and safety

Results posted to the registry on 14 Jan 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ArTiMist	16	15
Intravenous Quinine	15	15

Primary outcome: Parasitological Success Defined as a Reduction in Parasite Count of ≥ 90% of Baseline at 24 Hours After the First Dose

Time frame: 24 hours after first dose. Number. Unit: participants

Measure	ArTiMist n = 15	Intravenous Quinine n = 15
Value	14	10

ArTiMist vs Intravenous Quinine: difference between treatments: 26.7 (95% CI -0.3 to 53.7), p = 0.17, Fisher Exact

Population analysed: For the efficacy endpoints, the analysis was based on the Full Analysis Set (FAS) which was defined as all patients that received at least 1 dose of trial medication and had at least 1 post dose parasite count at 12 h (hours) or 24 h after start of treatment.

Primary outcome: Time for Parasite Count to Fall by 90% PCT(90)

Time frame: 3h (hours), 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h. Mean (Standard Deviation). Unit: hours

Measure	ArTiMist n = 15	Intravenous Quinine n = 15
Value	17.6 (7.34)	19.8 (13.59)

ArTiMist vs Intravenous Quinine: Hazard Ratio (HR): 1.05 (95% CI 0.48 to 3.01), p = 0.70, Log Rank

Primary outcome: Time for Parasite Count to Fall by 50% PCT(50)

Time frame: 3 h (hours) , 6h, 12h, 18h, 24h, 30h, 36h, 48h, 54h, 60h. Mean (Standard Deviation). Unit: hours

Measure	ArTiMist n = 15	Intravenous Quinine n = 15
Value	12.0 (6.48)	10.8 (7.42)

ArTiMist vs Intravenous Quinine: Hazard Ratio (HR): 0.92 (95% CI 0.34 to 2.18), p = 0.76, Log Rank

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the start of the study (01 December 2009) to the last study follow up visit on 19 January 2010. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ArTiMist	0 of 16 (0%)	13 of 16 (81.3%)	Not reported
Intravenous Quinine	1 of 15 (6.7%)	11 of 15 (73.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26303805Bendel 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.

Related trials for Falciparum Malaria

RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Not yet recruiting
Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
Malaria
Active, not recruitingPhase 4
Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics
Malaria,Falciparum, Malaria in Pregnancy
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
Malaria, Cerebral

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.

Daryl Bendel, MBChB MBA Dip Pharm Med MFPM study director

Xidea Solutions Limited

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Quinine and Artemether in people with Falciparum Malaria, run by Proto Pharma Ltd.

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 8 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 27 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 14 Jan 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?

Parasitological Success Defined as a Reduction in Parasite Count of ≥ 90% of Baseline at 24 Hours After the First Dose (time frame: 24 hours after first dose). The study lists 3 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 NCT01047436, 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 27 Jan 2011.