Trial Outcomes & Findings for Superiority of ArTiMist Versus Quinine in Children With Severe Malaria (NCT NCT01258049)
NCT ID: NCT01258049
Last Updated: 2014-02-28
Results Overview
Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
151 participants
Primary outcome timeframe
24 hours after start of treatment
Results posted on
2014-02-28
Participant Flow
Participant milestones
| Measure |
ArTiMist
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.
|
Quinine
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.
|
|---|---|---|
|
Overall Study
STARTED
|
77
|
74
|
|
Overall Study
COMPLETED
|
75
|
72
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Superiority of ArTiMist Versus Quinine in Children With Severe Malaria
Baseline characteristics by cohort
| Measure |
ArTiMist
n=77 Participants
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.
|
Quinine
n=74 Participants
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
n=151 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
2.8 years
STANDARD_DEVIATION 1.34 • n=99 Participants
|
2.5 years
STANDARD_DEVIATION 1.23 • n=107 Participants
|
2.6 years
STANDARD_DEVIATION 1.29 • n=206 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
79 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
72 Participants
n=206 Participants
|
|
Region of Enrollment
Ghana
|
25 participants
n=99 Participants
|
25 participants
n=107 Participants
|
50 participants
n=206 Participants
|
|
Region of Enrollment
Burkina Faso
|
25 participants
n=99 Participants
|
25 participants
n=107 Participants
|
50 participants
n=206 Participants
|
|
Region of Enrollment
Rwanda
|
27 participants
n=99 Participants
|
24 participants
n=107 Participants
|
51 participants
n=206 Participants
|
|
Disease Definition - Severe or complicated malaria
Severe or complicated malaria
|
49 participants
n=99 Participants
|
51 participants
n=107 Participants
|
100 participants
n=206 Participants
|
|
Disease Definition - Severe or complicated malaria
Uncomplicated malaria with GI complications
|
28 participants
n=99 Participants
|
23 participants
n=107 Participants
|
51 participants
n=206 Participants
|
|
Weight
|
11.7 kg
STANDARD_DEVIATION 2.4 • n=99 Participants
|
11.2 kg
STANDARD_DEVIATION 2.5 • n=107 Participants
|
11.4 kg
STANDARD_DEVIATION 2.5 • n=206 Participants
|
|
Pulse rate
|
146 bpm
STANDARD_DEVIATION 20.2 • n=99 Participants
|
147 bpm
STANDARD_DEVIATION 26.3 • n=107 Participants
|
146 bpm
STANDARD_DEVIATION 23.3 • n=206 Participants
|
|
Tympanic Temperature
|
38.6 Degrees Centigrade
STANDARD_DEVIATION 1.1 • n=99 Participants
|
38.6 Degrees Centigrade
STANDARD_DEVIATION 1.0 • n=107 Participants
|
38.6 Degrees Centigrade
STANDARD_DEVIATION 1.1 • n=206 Participants
|
|
Respiratory Rate
|
36.7 breaths/min
STANDARD_DEVIATION 11.0 • n=99 Participants
|
35.9 breaths/min
STANDARD_DEVIATION 11.3 • n=107 Participants
|
36.3 breaths/min
STANDARD_DEVIATION 11.2 • n=206 Participants
|
|
Blantyre Coma Scale
5
|
60 participants
n=99 Participants
|
53 participants
n=107 Participants
|
113 participants
n=206 Participants
|
|
Blantyre Coma Scale
< 5
|
17 participants
n=99 Participants
|
21 participants
n=107 Participants
|
38 participants
n=206 Participants
|
|
Parasite Counts
|
133884 p falciparum /mcl
STANDARD_DEVIATION 129715 • n=99 Participants
|
155321 p falciparum /mcl
STANDARD_DEVIATION 202213 • n=107 Participants
|
144602 p falciparum /mcl
STANDARD_DEVIATION 165964 • n=206 Participants
|
|
Parasite Count (median)
|
86572 p falciparum /mcl
n=99 Participants
|
66077 p falciparum /mcl
n=107 Participants
|
76325 p falciparum /mcl
n=206 Participants
|
PRIMARY outcome
Timeframe: 24 hours after start of treatmentPopulation: 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
Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Parasitological Success (MITT)
Success
|
66 participants
|
28 participants
|
|
Parasitological Success (MITT)
Not Success
|
4 participants
|
43 participants
|
PRIMARY outcome
Timeframe: 24 hours after start of treatmentPopulation: 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.
Parasitological success defined as a reduction in parasite count of ≥ 90% of baseline at 24 hours after the first dose
Outcome measures
| Measure |
ArTiMist
n=68 Participants
|
Quinine
n=69 Participants
|
|---|---|---|
|
Parasitological Success (PP)
Success
|
65 participants
|
28 participants
|
|
Parasitological Success (PP)
Not Success
|
3 participants
|
41 participants
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentParasite 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
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Parasite Clearance Time (PCT) [MITT Population]
|
30.29 hours
Standard Deviation 13.21
|
68.30 hours
Standard Deviation 98.04
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentTime for parasite counts to fall by 90%
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
PCT 90 [MITT Population]
|
15.02 hours
Standard Deviation 5.82
|
27.93 hours
Standard Deviation 18.03
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentTime for parasite counts to fall by 50%
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
PCT 50 [MITT Population]
|
9.42 hours
Standard Deviation 5.72
|
18.58 hours
Standard Deviation 9.19
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentThe percentage reduction in parasite counts 24 hours after first dose
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
PRR 24 [MITT Population]
|
98.2 percentage of baseline
Standard Deviation 6.12
|
44.5 percentage of baseline
Standard Deviation 114.27
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentThe percentage reduction in parasite counts 12 hours after first dose
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
PRR 12 [MITT Population]
|
47.6 percentage of baseline
Standard Deviation 70.28
|
-132.2 percentage of baseline
Standard Deviation 765.92
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentTime in hours from the initiation of therapy until the disappearance of fever (tympanic temperature \< 38.0) that lasted at least 24 hours.
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Fever Clearance Time (FCT)
|
42.6 hours
Standard Deviation 34.47
|
41.6 hours
Standard Deviation 22.73
|
SECONDARY outcome
Timeframe: 28 days after the start of treatmentPopulation: For some subjects, this endpoint was not evaluable and/or not all data was received.
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
Outcome measures
| Measure |
ArTiMist
n=55 Participants
|
Quinine
n=63 Participants
|
|---|---|---|
|
Complete Cure Rate
Cure
|
41 participants
|
46 participants
|
|
Complete Cure Rate
No Cure
|
14 participants
|
17 participants
|
SECONDARY outcome
Timeframe: Three days after the start of treatmentEarly 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
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Early Treatment Failure
|
0 participants
|
14 participants
|
SECONDARY outcome
Timeframe: 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
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Late Clinical Failure
|
3 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 28 days after the start of treatmento Parasitaemia on any day from Day 7 to Day 28 and tympanic temperature ≤ 38.0°C
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Late Parasitological Failure
|
12 participants
|
14 participants
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentTime 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
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Time to Return to Full Consciousness
|
20.8 hours
Standard Deviation 9.58
|
23.0 hours
Standard Deviation 16.52
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentTime 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.
Outcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Time to Return to Normal Per os Status
|
22.1 hours
Standard Deviation 12.89
|
25.3 hours
Standard Deviation 16.28
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentOutcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events, of Possible, Probably and Definite Causalities
|
5 participants
|
6 participants
|
SECONDARY outcome
Timeframe: 28 days after start of treatmentOutcome measures
| Measure |
ArTiMist
n=70 Participants
|
Quinine
n=71 Participants
|
|---|---|---|
|
Number of Deaths or Neurological Sequelae at Day 28
|
0 participants
|
0 participants
|
Adverse Events
ArTiMist
Serious events: 4 serious events
Other events: 43 other events
Deaths: 0 deaths
Quinine
Serious events: 10 serious events
Other events: 44 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ArTiMist
n=77 participants at risk
|
Quinine
n=74 participants at risk
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
2.6%
2/77 • Number of events 2 • 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.
|
9.5%
7/74 • Number of events 7 • 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.
|
|
Infections and infestations
Bronchopneumonia
|
1.3%
1/77 • Number of events 1 • 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.
|
0.00%
0/74 • 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.
|
|
Infections and infestations
Cerebral Malaria
|
0.00%
0/77 • 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.
|
1.4%
1/74 • Number of events 1 • 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.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/77 • 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.
|
1.4%
1/74 • Number of events 1 • 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.
|
|
Infections and infestations
Malaria
|
0.00%
0/77 • 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.
|
1.4%
1/74 • Number of events 1 • 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.
|
|
Infections and infestations
Sepsis
|
1.3%
1/77 • Number of events 1 • 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.
|
0.00%
0/74 • 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.
|
Other adverse events
| Measure |
ArTiMist
n=77 participants at risk
|
Quinine
n=74 participants at risk
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.8%
6/77 • Number of events 6 • 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.
|
16.2%
12/74 • Number of events 12 • 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.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/77 • 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.
|
5.4%
4/74 • Number of events 4 • 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.
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
5/77 • Number of events 5 • 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.
|
2.7%
2/74 • Number of events 2 • 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.
|
|
General disorders
Pyrexia
|
9.1%
7/77 • Number of events 7 • 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.
|
8.1%
6/74 • Number of events 6 • 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.
|
|
Infections and infestations
Malaria
|
22.1%
17/77 • Number of events 17 • 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.
|
18.9%
14/74 • Number of events 14 • 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.
|
|
Infections and infestations
Respiratory Tract Infection
|
9.1%
7/77 • Number of events 7 • 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.
|
4.1%
3/74 • Number of events 3 • 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.
|
|
Renal and urinary disorders
Proteinuria
|
1.3%
1/77 • Number of events 1 • 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.
|
5.4%
4/74 • Number of events 4 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.8%
6/77 • Number of events 6 • 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.
|
2.7%
2/74 • Number of events 2 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
5.2%
4/77 • Number of events 4 • 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.
|
2.7%
2/74 • Number of events 2 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place