Superiority of ArTiMist Versus Quinine in Children With Severe Malaria

• Sponsor: Proto Pharma Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01258049
• Collaborator: (none)
• Enrollment: 151
• Locations: 3
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 50.3
• Patients Per Site Per Month: 2.4

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Plasmodium Falciparum Malaria	Drug: Artemether Sublingual Spray; Drug: Quinine	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Dec 1, 2010
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ArTiMist	Drug: Artemether Sublingual Spray; Artemether sublingual spray administered at 3 mg/kg (milligrams per kilogram) at specified timepoints; Other Names: ArTiMist
Active Comparator: Quinine	Drug: Quinine; Quinine administered intravenously, 20 mg/kg loading dose followed by 10 mg/kg every eight hours

Outcome Measures

Primary Outcome Measures

1. Parasitological Success (MITT) [24 hours after start of treatment]

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

2. Parasitological Success (PP) [24 hours after start of treatment]

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

Secondary Outcome Measures

1. Parasite Clearance Time (PCT) [MITT Population] [28 days after start of treatment]

   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

2. PCT 90 [MITT Population] [28 days after start of treatment]

   Time for parasite counts to fall by 90%

3. PCT 50 [MITT Population] [28 days after start of treatment]

   Time for parasite counts to fall by 50%

4. PRR 24 [MITT Population] [28 days after start of treatment]

   The percentage reduction in parasite counts 24 hours after first dose

5. PRR 12 [MITT Population] [28 days after start of treatment]

   The percentage reduction in parasite counts 12 hours after first dose

6. Fever Clearance Time (FCT) [28 days after start of treatment]

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

7. Complete Cure Rate [28 days after the start of treatment]

   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

8. Early Treatment Failure [Three days after the start of treatment]

   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

9. Late Clinical Failure [28 days after the start of treatment]

   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

10. Late Parasitological Failure [28 days after the start of treatment]

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

11. Time to Return to Full Consciousness [28 days after start of treatment]

    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

12. Time to Return to Normal Per os Status [28 days after start of treatment]

    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.

13. Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events, of Possible, Probably and Definite Causalities [28 days after start of treatment]

14. Number of Deaths or Neurological Sequelae at Day 28 [28 days after start of treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 .

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre National de Recherche et de Formation sur le Paludisme (CNRFP)	Ouagadougou		Burkina Faso	01 BP 2208
2	Navrongo Health Research Centre	Navrongo		Ghana	P.O. Box 114
3	Rwinkwavu District Hospital	Rwinkwavu	Eastern Province	Rwanda

Sponsors and Collaborators

• Proto Pharma Ltd

Investigators

• Study Chair: Daryl Bendel, MBChB MFPM, Xidea Solutions Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Proto Pharma Ltd
• ClinicalTrials.gov Identifier: NCT01258049
• Other Study ID Numbers: ART004
• First Posted: Dec 10, 2010
• Last Update Posted: Feb 28, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Proto Pharma Ltd: Plasmodium infections; Remittent fever; Artemether; Artemesinins; Quinine; Malaria; Protozoan infections; sublingual drug delivery; Parasitic disease; Antiprotozoan agents
• Additional relevant MeSH terms: Malaria; Malaria, Falciparum; Artemether; Quinine

Study Results

Participant Flow

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description	Doses of 3 mg/kg were administered sublingually at: 0 h, 8 h, 24 h, 36 h, 48 h, and 60 h. Following the initial six doses, subjects could, at the discretion of the Investigator receive a further four daily doses of 3 mg/kg ArTiMist™ to complete a seven day treatment course, or be converted to another suitable treatment or a suitable course of combination therapy in accordance with national drugs policy where applicable.	A loading dose of 20 mg/kg was given over four hours and thereafter 10 mg/kg was given every eight hours until the subject was able to swallow. Thereafter, patients were given quinine syrup or crushed tablets (10 mg/kg every eight hours) or another suitable treatment to ensure they received at least seven days of therapy, or be converted to another suitable treatment or a suitable course of combination therapy, in accordance with national drugs policy where applicable.
Period Title: Overall Study
STARTED	77	74
COMPLETED	75	72
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	ArTiMist	Quinine	Total
Arm/Group Description	Doses of 3 mg/kg were administered sublingually at: 0 h, 8 h, 24 h, 36 h, 48 h, and 60 h. Following the initial six doses, subjects could, at the discretion of the Investigator receive a further four daily doses of 3 mg/kg ArTiMist™ to complete a seven day treatment course, or be converted to another suitable treatment or a suitable course of combination therapy in accordance with national drugs policy where applicable.	A loading dose of 20 mg/kg was given over four hours and thereafter 10 mg/kg was given every eight hours until the subject was able to swallow. Thereafter, patients were given quinine syrup or crushed tablets (10 mg/kg every eight hours) or another suitable treatment to ensure they received at least seven days of therapy, or be converted to another suitable treatment or a suitable course of combination therapy, in accordance with national drugs policy where applicable	Total of all reporting groups
Overall Participants	77	74	151
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	2.8 (1.34)	2.5 (1.23)	2.6 (1.29)
Sex: Female, Male (Count of Participants)
Female	40 51.9%	39 52.7%	79 52.3%
Male	37 48.1%	35 47.3%	72 47.7%
Region of Enrollment (participants) [Number]
Ghana	25 32.5%	25 33.8%	50 33.1%
Burkina Faso	25 32.5%	25 33.8%	50 33.1%
Rwanda	27 35.1%	24 32.4%	51 33.8%
Disease Definition - Severe or complicated malaria (participants) [Number]
Severe or complicated malaria	49 63.6%	51 68.9%	100 66.2%
Uncomplicated malaria with GI complications	28 36.4%	23 31.1%	51 33.8%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	11.7 (2.4)	11.2 (2.5)	11.4 (2.5)
Pulse rate (bpm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [bpm]	146 (20.2)	147 (26.3)	146 (23.3)
Tympanic Temperature (Degrees Centigrade) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Degrees Centigrade]	38.6 (1.1)	38.6 (1.0)	38.6 (1.1)
Respiratory Rate (breaths/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [breaths/min]	36.7 (11.0)	35.9 (11.3)	36.3 (11.2)
Blantyre Coma Scale (participants) [Number]
5	60 77.9%	53 71.6%	113 74.8%
< 5	17 22.1%	21 28.4%	38 25.2%
Parasite Counts (p falciparum /mcl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [p falciparum /mcl]	133884 (129715)	155321 (202213)	144602 (165964)
Parasite Count (median) (p falciparum /mcl) [Median (Full Range) ]
Median (Full Range) [p falciparum /mcl]	86572	66077	76325

Outcome Measures

1. Primary Outcome

Title	Parasitological Success (MITT)
Description	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 start of treatment

Outcome Measure Data

Analysis Population Description

The Modified Intention to Treat (MITT) population included all randomised subjects who received at least one dose of study medication and had evaluable parasite counts at 24 hours after first dosing. 7 subjects for ArTiMist and 3 subjects for quinine were excluded due to no baseline or 24 h parasite count

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Success	66 85.7%	28 37.8%
Not Success	4 5.2%	43 58.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments	In ART003, the parasite success rate for quinine was 67.7%. On the assumption that the parasite success rate was 70% for quinine in this study and in order to demonstrate that ArTiMist™ is superior to quinine by at least 20% the success rate for ArTiMist™ should be at least 90%. Using these figures, and assuming a power of 80%, an alpha of 0.05 (two sided) and based on an equal allocation to the ArTiMist™ and quinine treatment arms, the number of subjects (n) required on each treatment was 59.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.005
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	54.85
	Confidence Interval	(2-Sided) 95%; 42.25 to 67.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Parasite Clearance Time (PCT) [MITT Population]
Description	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
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [hours]	30.29 (13.21)	68.30 (98.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-38.97
	Confidence Interval	(2-Sided) 95%; -62.22 to -15.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	PCT 90 [MITT Population]
Description	Time for parasite counts to fall by 90%
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [hours]	15.02 (5.82)	27.93 (18.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.91
	Confidence Interval	(2-Sided) 95%; -17.38 to -8.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	PCT 50 [MITT Population]
Description	Time for parasite counts to fall by 50%
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [hours]	9.42 (5.72)	18.58 (9.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.005
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.16
	Confidence Interval	(2-Sided) 95%; -11.71 to - 6.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	PRR 24 [MITT Population]
Description	The percentage reduction in parasite counts 24 hours after first dose
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [percentage of baseline]	98.2 (6.12)	44.5 (114.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	54.02
	Confidence Interval	(2-Sided) 95%; 27.05 to 80.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	PRR 12 [MITT Population]
Description	The percentage reduction in parasite counts 12 hours after first dose
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [percentage of baseline]	47.6 (70.28)	-132.2 (765.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	174.09
	Confidence Interval	(2-Sided) 95%; -10.44 to 358.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	mean parasite counts increased in the first 12 hours for patients on quinine treatment

7. Secondary Outcome

Title	Fever Clearance Time (FCT)
Description	Time in hours from the initiation of therapy until the disappearance of fever (tympanic temperature < 38.0) that lasted at least 24 hours.
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [hours]	42.6 (34.47)	41.6 (22.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; -10.16 to 12.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Complete Cure Rate
Description	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
Time Frame	28 days after the start of treatment

Outcome Measure Data

Analysis Population Description

For some subjects, this endpoint was not evaluable and/or not all data was received.

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	55	63
Cure	41 53.2%	46 62.2%
No Cure	14 18.2%	17 23%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.42 to 2.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Early Treatment Failure
Description	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
Time Frame	Three days after the start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Number [participants]	0 0%	14 18.9%

10. Secondary Outcome

Title	Late Clinical Failure
Description	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
Time Frame	28 days after the start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Number [participants]	3 3.9%	1 1.4%

11. Primary Outcome

Title	Parasitological Success (PP)
Description	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 start of treatment

Outcome Measure Data

Analysis Population Description

The Per Protocol (PP) population included the subjects in the MITT population who had received at least 80% of doses up to the time of discharge from the hospital, had evaluable data up to and including Day 28 and had no major protocol violations.

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	68	69
Success	65 84.4%	28 37.8%
Not Success	3 3.9%	41 55.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ArTiMist, Quinine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.005
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	55.01
	Confidence Interval	(2-Sided) 95%; 42.44 to 67.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Late Parasitological Failure
Description	o Parasitaemia on any day from Day 7 to Day 28 and tympanic temperature ≤ 38.0°C
Time Frame	28 days after the start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Number [participants]	12 15.6%	14 18.9%

13. Secondary Outcome

Title	Time to Return to Full Consciousness
Description	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
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [hours]	20.8 (9.58)	23.0 (16.52)

14. Secondary Outcome

Title	Time to Return to Normal Per os Status
Description	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.
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Mean (Standard Deviation) [hours]	22.1 (12.89)	25.3 (16.28)

15. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events, of Possible, Probably and Definite Causalities
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Number [participants]	5 6.5%	6 8.1%

16. Secondary Outcome

Title	Number of Deaths or Neurological Sequelae at Day 28
Time Frame	28 days after start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ArTiMist	Quinine
Arm/Group Description
Measure Participants	70	71
Number [participants]	0 0%	0 0%

Adverse Events

Time Frame	Adverse events were reported from the time of signing informed consent until the final study visit. Adverse events that started or worsened after start of treatment were considered Treatment Emergent.
Arm/Group Title	ArTiMist		Quinine
Arm/Group Description
All Cause Mortality
	ArTiMist		Quinine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ArTiMist		Quinine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/77 (5.2%)		10/74 (13.5%)
Blood and lymphatic system disorders
Anaemia	2/77 (2.6%)	2	7/74 (9.5%)	7
Infections and infestations
Bronchopneumonia	1/77 (1.3%)	1	0/74 (0%)	0
Cerebral Malaria	0/77 (0%)	0	1/74 (1.4%)	1
Gastroenteritis	0/77 (0%)	0	1/74 (1.4%)	1
Malaria	0/77 (0%)	0	1/74 (1.4%)	1
Sepsis	1/77 (1.3%)	1	0/74 (0%)	0
Other (Not Including Serious) Adverse Events
	ArTiMist		Quinine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/77 (55.8%)		44/74 (59.5%)
Blood and lymphatic system disorders
Anaemia	6/77 (7.8%)	6	12/74 (16.2%)	12
Gastrointestinal disorders
Abdominal pain	0/77 (0%)	0	4/74 (5.4%)	4
Vomiting	5/77 (6.5%)	5	2/74 (2.7%)	2
General disorders
Pyrexia	7/77 (9.1%)	7	6/74 (8.1%)	6
Infections and infestations
Malaria	17/77 (22.1%)	17	14/74 (18.9%)	14
Respiratory Tract Infection	7/77 (9.1%)	7	3/74 (4.1%)	3
Renal and urinary disorders
Proteinuria	1/77 (1.3%)	1	4/74 (5.4%)	4
Respiratory, thoracic and mediastinal disorders
Cough	6/77 (7.8%)	6	2/74 (2.7%)	2
Bronchitis	4/77 (5.2%)	4	2/74 (2.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.