Trial Outcomes & Findings for Seasonal Malaria Vaccination (RTS,S/AS01) and Seasonal Malaria Chemoprevention (SP/AQ) (NCT NCT03143218)
NCT ID: NCT03143218
Last Updated: 2022-04-07
Results Overview
Passive surveillance to detect episode of fever (temperature \> 37.5 C), or a history of fever within the past 48 hours, that is severe enough to require treatment at a health centre and which is accompanied by a positive blood film with a parasite density of 5,000 per µl or more
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
5920 participants
Primary outcome timeframe
Passive surveillance of clinical episodes of malaria within the study area starting from the date of the first dose of study vaccines (April/May 2017) until 31st March 2020- a total of 36 months.
Results posted on
2022-04-07
Participant Flow
Participant milestones
| Measure |
SMC With SP+AQ
Administration of RABIPUR® in Year 1 and Hepatitis A vaccine in Year 2 and 3, followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RABIPUR®: Year 1 (2017) Three doses of rabies vaccine (April, May, June) Year 2 and 3 (2018/19) One dose of Hepatitis A vaccine (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
RTS,S/AS01
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC placebo: Year 1, 2 and 3(2017/18/19) Four cycles of SMC placebo during the malaria transmission season
|
RTS,S/AS01 PLUS SMC With SP+AQ
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
|---|---|---|---|
|
Overall Study
STARTED
|
1965
|
1988
|
1967
|
|
Overall Study
COMPLETED
|
1716
|
1734
|
1740
|
|
Overall Study
NOT COMPLETED
|
249
|
254
|
227
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
SMC With SP+AQ
n=1965 Participants
Administration of RABIPUR® in Year 1 and Hepatitis A vaccine in Year 2 and 3, followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RABIPUR®: Year 1 (2017) Three doses of rabies vaccine (April, May, June) Year 2 and 3 (2018/19) One dose of Hepatitis A vaccine (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
RTS,S/AS01
n=1988 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC placebo: Year 1, 2 and 3(2017/18/19) Four cycles of SMC placebo during the malaria transmission season
|
RTS,S/AS01 PLUS SMC With SP+AQ
n=1967 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
Total
n=5920 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
Under 8 months
|
471 Participants
n=1965 Participants
|
448 Participants
n=1988 Participants
|
463 Participants
n=1967 Participants
|
1382 Participants
n=5920 Participants
|
|
Age, Customized
8-11 months
|
532 Participants
n=1965 Participants
|
527 Participants
n=1988 Participants
|
531 Participants
n=1967 Participants
|
1590 Participants
n=5920 Participants
|
|
Age, Customized
12-15 months
|
486 Participants
n=1965 Participants
|
552 Participants
n=1988 Participants
|
537 Participants
n=1967 Participants
|
1575 Participants
n=5920 Participants
|
|
Age, Customized
16 months or older
|
476 Participants
n=1965 Participants
|
461 Participants
n=1988 Participants
|
436 Participants
n=1967 Participants
|
1373 Participants
n=5920 Participants
|
|
Sex: Female, Male
Female
|
950 Participants
n=1965 Participants
|
956 Participants
n=1988 Participants
|
948 Participants
n=1967 Participants
|
2854 Participants
n=5920 Participants
|
|
Sex: Female, Male
Male
|
1015 Participants
n=1965 Participants
|
1032 Participants
n=1988 Participants
|
1019 Participants
n=1967 Participants
|
3066 Participants
n=5920 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Burkina Faso
|
936 participants
n=1965 Participants
|
911 participants
n=1988 Participants
|
930 participants
n=1967 Participants
|
2777 participants
n=5920 Participants
|
|
Region of Enrollment
Mali
|
1029 participants
n=1965 Participants
|
1077 participants
n=1988 Participants
|
1037 participants
n=1967 Participants
|
3143 participants
n=5920 Participants
|
|
LLIN use the night before the 2017 census
Yes
|
1593 Participants
n=1965 Participants
|
1580 Participants
n=1988 Participants
|
1577 Participants
n=1967 Participants
|
4750 Participants
n=5920 Participants
|
|
LLIN use the night before the 2017 census
No
|
360 Participants
n=1965 Participants
|
391 Participants
n=1988 Participants
|
380 Participants
n=1967 Participants
|
1131 Participants
n=5920 Participants
|
|
LLIN use the night before the 2017 census
Missing
|
12 Participants
n=1965 Participants
|
17 Participants
n=1988 Participants
|
10 Participants
n=1967 Participants
|
39 Participants
n=5920 Participants
|
|
PCV vaccination
Yes
|
1650 Participants
n=1965 Participants
|
1646 Participants
n=1988 Participants
|
1642 Participants
n=1967 Participants
|
4938 Participants
n=5920 Participants
|
|
PCV vaccination
No
|
82 Participants
n=1965 Participants
|
99 Participants
n=1988 Participants
|
74 Participants
n=1967 Participants
|
255 Participants
n=5920 Participants
|
|
PCV vaccination
Card not available
|
172 Participants
n=1965 Participants
|
175 Participants
n=1988 Participants
|
171 Participants
n=1967 Participants
|
518 Participants
n=5920 Participants
|
|
PCV vaccination
Card available but incomplete
|
61 Participants
n=1965 Participants
|
67 Participants
n=1988 Participants
|
79 Participants
n=1967 Participants
|
207 Participants
n=5920 Participants
|
|
PCV vaccination
Missing
|
0 Participants
n=1965 Participants
|
1 Participants
n=1988 Participants
|
1 Participants
n=1967 Participants
|
2 Participants
n=5920 Participants
|
|
Penta vaccination
Yes
|
1650 Participants
n=1965 Participants
|
1647 Participants
n=1988 Participants
|
1650 Participants
n=1967 Participants
|
4947 Participants
n=5920 Participants
|
|
Penta vaccination
No
|
87 Participants
n=1965 Participants
|
95 Participants
n=1988 Participants
|
78 Participants
n=1967 Participants
|
260 Participants
n=5920 Participants
|
|
Penta vaccination
Card not available
|
169 Participants
n=1965 Participants
|
179 Participants
n=1988 Participants
|
167 Participants
n=1967 Participants
|
515 Participants
n=5920 Participants
|
|
Penta vaccination
Card available but incomplete
|
58 Participants
n=1965 Participants
|
66 Participants
n=1988 Participants
|
67 Participants
n=1967 Participants
|
191 Participants
n=5920 Participants
|
|
Penta vaccination
Missing
|
1 Participants
n=1965 Participants
|
1 Participants
n=1988 Participants
|
5 Participants
n=1967 Participants
|
7 Participants
n=5920 Participants
|
|
MenAfriVac vaccination
Yes
|
468 Participants
n=1965 Participants
|
477 Participants
n=1988 Participants
|
478 Participants
n=1967 Participants
|
1423 Participants
n=5920 Participants
|
|
MenAfriVac vaccination
No
|
1245 Participants
n=1965 Participants
|
1251 Participants
n=1988 Participants
|
1251 Participants
n=1967 Participants
|
3747 Participants
n=5920 Participants
|
|
MenAfriVac vaccination
Missing
|
252 Participants
n=1965 Participants
|
260 Participants
n=1988 Participants
|
238 Participants
n=1967 Participants
|
750 Participants
n=5920 Participants
|
PRIMARY outcome
Timeframe: Passive surveillance of clinical episodes of malaria within the study area starting from the date of the first dose of study vaccines (April/May 2017) until 31st March 2020- a total of 36 months.Passive surveillance to detect episode of fever (temperature \> 37.5 C), or a history of fever within the past 48 hours, that is severe enough to require treatment at a health centre and which is accompanied by a positive blood film with a parasite density of 5,000 per µl or more
Outcome measures
| Measure |
SMC With SP+AQ
n=1965 Participants
Administration of RABIPUR® in Year 1 and Hepatitis A vaccine in Year 2 and 3, followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RABIPUR®: Year 1 (2017) Three doses of rabies vaccine (April, May, June) Year 2 and 3 (2018/19) One dose of Hepatitis A vaccine (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
RTS,S/AS01
n=1988 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC placebo: Year 1, 2 and 3(2017/18/19) Four cycles of SMC placebo during the malaria transmission season
|
RTS,S/AS01 PLUS SMC With SP+AQ
n=1967 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
|---|---|---|---|
|
Incidence of Clinical Episodes of Malaria
|
304.8 No. of events/1000 person years at risk
Interval 290.5 to 319.8
|
278.2 No. of events/1000 person years at risk
Interval 264.6 to 292.4
|
113.3 No. of events/1000 person years at risk
Interval 104.7 to 122.5
|
SECONDARY outcome
Timeframe: Passive surveillance in all health centers within the study area, active surveillance in a sub set of study children starting July 2017 till April 2020.Passive and active surveillance to detect cases with temperature \> 37.5o C), or a history of fever within the past 48 hours, with a positive blood film (any level of asexual parasitaemia) or a positive rapid diagnostic test (RDT) for malaria
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion (30 months), each child admitted in a study hospital will be treated and monitored until complete cure or death (a period of 3 years). Documentation of each hospital admission according to ICH-GCP.Hospital admissions with malaria, including cases of severe malaria which meet WHO criteria for a diagnosis of severe malaria.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Weekly home visits through study completion from July 2017 - April 2020 to screen study children for malaria.Active surveillance of malaria at household level to assess the prevalence of malaria infection not severe enough to warrant a clinic visit detected in a subset of randomly selected children.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Blood sample collection during 2-week cross sectional survey at the end of each malaria transmission season.The prevalence of malaria parasitaemia, including gametocytaemia, moderate and severe anaemia and malnutrition at the end of the malaria transmission season
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Through study completion (for 30 months), each SAE will be treated and documented according to ICH-GCP.Serious adverse events (SAEs), including any deaths, occurring at any time during the study with special reference to any cases of meningitis and cerebral malaria (WHO case definition)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Blood sample collection prior to 1st dose of vaccine and 1 month after 3rd dose of the primary series of vaccination. In years 2 and 3 blood will be collected before the booster dose and 1 month after administration of the 4th (and 5th) vaccine dose.After priming and after each booster dose, determined in a sub-sample of children
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Blood sample collection during the 2-week cross sectional survey conducted at the end of malaria transmission season in 2019.The presence of molecular markers of resistance to SP and AQ in parasite positive samples
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Blood sample collection during the 2-week cross sectional survey at the end of the malaria transmission season in Year 2 and 3 (November 2018/19).The prevalence of malaria parasitaemia at the end of the malaria transmission season in school-age children resident in the study areas, to determine overall malaria transmission
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Children with asymptomatic malaria parasitaemia identified during the final cross-sectional survey (November 2019), treated with a full course of SP+AQ over 3 days and followed for 28 days.The 28-day treatment outcome in children with asymptomatic malaria parasitaemia treated with SP+AQ.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Data collection in Year 3The acceptability of the two interventions (separately and combined) to the health care deliverers and to the study communities (standardized questionnaires)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Data collection in Year 3The feasibility of introducing two malaria control strategies simultaneously from the health system perspective (structured observations and interviews with health system officials)
Outcome measures
Outcome data not reported
Adverse Events
SMC With SP+AQ
Serious events: 97 serious events
Other events: 0 other events
Deaths: 32 deaths
RTS,S/AS01
Serious events: 94 serious events
Other events: 0 other events
Deaths: 27 deaths
RTS,S/AS01 PLUS SMC With SP+AQ
Serious events: 71 serious events
Other events: 0 other events
Deaths: 15 deaths
Serious adverse events
| Measure |
SMC With SP+AQ
n=1965 participants at risk
Administration of RABIPUR® in Year 1 and Hepatitis A vaccine in Year 2 and 3, followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RABIPUR®: Year 1 (2017) Three doses of rabies vaccine (April, May, June) Year 2 and 3 (2018/19) One dose of Hepatitis A vaccine (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
RTS,S/AS01
n=1988 participants at risk
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC placebo: Year 1, 2 and 3(2017/18/19) Four cycles of SMC placebo during the malaria transmission season
|
RTS,S/AS01 PLUS SMC With SP+AQ
n=1967 participants at risk
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1,2 and 3.
RTS,S/AS01: Year 1 (2017) Three doses of RTSS/AS01 (April, May, June) Year 2 and 3 (2018/19) One booster dose of RTSS/AS01 (June)
SMC with SP+AQ: Year 1, 2 and 3(2017/18/19) Four cycles of SMC (SP+AQ) during the malaria transmission season One cycle of SMC for children above one year of age consisting of sulphadoxine - pyrimethamin (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. Infants will receive half of these doses.
|
|---|---|---|---|
|
General disorders
Non-fatal SAEs
|
3.3%
65/1965 • Serious adverse event data were collected over a 3 year period, from 1st April 2017 to 31st March 2020.
The number of participants at risk for other (non-serious) adverse events is zero because non-serious adverse events were not collected or assessed as part of this study.
|
3.4%
67/1988 • Serious adverse event data were collected over a 3 year period, from 1st April 2017 to 31st March 2020.
The number of participants at risk for other (non-serious) adverse events is zero because non-serious adverse events were not collected or assessed as part of this study.
|
2.8%
56/1967 • Serious adverse event data were collected over a 3 year period, from 1st April 2017 to 31st March 2020.
The number of participants at risk for other (non-serious) adverse events is zero because non-serious adverse events were not collected or assessed as part of this study.
|
|
General disorders
Fatal SAEs
|
1.6%
32/1965 • Serious adverse event data were collected over a 3 year period, from 1st April 2017 to 31st March 2020.
The number of participants at risk for other (non-serious) adverse events is zero because non-serious adverse events were not collected or assessed as part of this study.
|
1.4%
27/1988 • Serious adverse event data were collected over a 3 year period, from 1st April 2017 to 31st March 2020.
The number of participants at risk for other (non-serious) adverse events is zero because non-serious adverse events were not collected or assessed as part of this study.
|
0.76%
15/1967 • Serious adverse event data were collected over a 3 year period, from 1st April 2017 to 31st March 2020.
The number of participants at risk for other (non-serious) adverse events is zero because non-serious adverse events were not collected or assessed as part of this study.
|
Other adverse events
Adverse event data not reported
Additional Information
Professor Brian Greenwood
London School of Hygiene and Tropical Medicine
Phone: +442072994707
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place