Trial Outcomes & Findings for Seasonal Malaria Vaccination (RTS,S/AS01) and Seasonal Malaria Chemoprevention (SP/AQ) Extension Study (NCT NCT04319380)
NCT ID: NCT04319380
Last Updated: 2024-09-20
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
5098 participants
Primary outcome timeframe
Passive surveillance of clinical episodes of malaria within the study area over 24 months (1 April 2020 until 31 March 2022).
Results posted on
2024-09-20
Participant Flow
Participant milestones
| Measure |
SMC With SP+AQ
Administration of tetanus/diphtheria toxoids vaccine followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
Tetanus/diphtheria toxoids: One dose of tetanus/diphtheria toxoids vaccine (June) in year 1 and year 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
|
RTS,S/AS01
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1 and 2.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
SMC placebo: Year 1 and 2 (2020/21) Four cycles of SMC placebo (July, August, September, October). In Year 2 (2021), a fifth cycle of SMC placebo was given to children in Burkina Faso in line with national guidelines.
|
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 and 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
|
|---|---|---|---|
|
Overall Study
STARTED
|
1683
|
1705
|
1710
|
|
Overall Study
COMPLETED
|
1644
|
1650
|
1661
|
|
Overall Study
NOT COMPLETED
|
39
|
55
|
49
|
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=1683 Participants
Administration of tetanus/diphtheria toxoids vaccine followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
Tetanus/diphtheria toxoids: One dose of tetanus/diphtheria toxoids vaccine (June) in year 1 and year 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
|
RTS,S/AS01
n=1705 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1 and 2.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
SMC placebo: Year 1 and 2 (2020/21) Four cycles of SMC placebo (July, August, September, October). In Year 2 (2021), a fifth cycle of SMC placebo was given to children in Burkina Faso in line with national guidelines.
|
RTS,S/AS01 Plus SMC With SP+AQ
n=1710 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
|
Total
n=5098 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
48.6 Months
STANDARD_DEVIATION 4.3 • n=1683 Participants
|
48.8 Months
STANDARD_DEVIATION 4.2 • n=1705 Participants
|
48.6 Months
STANDARD_DEVIATION 4.2 • n=1710 Participants
|
48.7 Months
STANDARD_DEVIATION 4.2 • n=5098 Participants
|
|
Sex: Female, Male
Female
|
817 Participants
n=1683 Participants
|
813 Participants
n=1705 Participants
|
830 Participants
n=1710 Participants
|
2460 Participants
n=5098 Participants
|
|
Sex: Female, Male
Male
|
866 Participants
n=1683 Participants
|
892 Participants
n=1705 Participants
|
880 Participants
n=1710 Participants
|
2638 Participants
n=5098 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Burkina Faso
|
824 participants
n=1683 Participants
|
813 participants
n=1705 Participants
|
837 participants
n=1710 Participants
|
2474 participants
n=5098 Participants
|
|
Region of Enrollment
Mali
|
859 participants
n=1683 Participants
|
892 participants
n=1705 Participants
|
873 participants
n=1710 Participants
|
2624 participants
n=5098 Participants
|
PRIMARY outcome
Timeframe: Passive surveillance of clinical episodes of malaria within the study area over 24 months (1 April 2020 until 31 March 2022).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=1683 Participants
Administration of tetanus/diphtheria toxoids vaccine followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
Tetanus/diphtheria toxoids: One dose of tetanus/diphtheria toxoids vaccine (June) in year 1 and year 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
|
RTS,S/AS01
n=1705 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1 and 2.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
SMC placebo: Year 1 and 2 (2020/21) Four cycles of SMC placebo (July, August, September, October). In Year 2 (2021), a fifth cycle of SMC placebo was given to children in Burkina Faso in line with national guidelines.
|
RTS,S/AS01 Plus SMC With SP+AQ
n=1710 Participants
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
|
|---|---|---|---|
|
Incidence of Clinical Episodes of Malaria
|
338.1 Episodes per 1,000 child years at risk
Interval 315.4 to 362.2
|
421.3 Episodes per 1,000 child years at risk
Interval 395.5 to 448.2
|
178.9 Episodes per 1,000 child years at risk
Interval 162.5 to 196.7
|
SECONDARY outcome
Timeframe: Passive surveillance in all health centers within the study area starting 1 April 2020 until 31 March 2022.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, each child admitted in a study hospital will be treated and monitored until complete cure or death (a period of 2 years). Documentation of each hospital admission according to ICH-GCPHospital 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: Blood sample collection during 2-week cross sectional survey at the end of each malaria transmission season (November 2020/21).).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 2 years), 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 0-7 days before and one month after the booster doses (year 1 and 2).Anti-CSP antibody concentrations obtained before 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 at the end of each malaria transmission season (November 2020/21).The prevalence of malaria parasitaemia at the end of each 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: Blood sample collection from children with clinical episodes of malaria and in children with parasitaemia at the 2-week cross-sectional survey (November 2020/21)).The prevalence of mutations in the Th2 or Th3 locus of the Plasmodium falciparum csp gene in isolates from children who have received RTS,S/AS01 that differ from those of the isolate used in the preparation of the vaccine
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Blood sample collection during the final 2-week cross sectional survey conducted at the end of malaria transmission season (November 2021)The presence of molecular markers of resistance to SP and AQ in parasite positive samples
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Children with asymptomatic malaria parasitaemia identified during the final cross-sectional survey (November 2021), 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
Adverse Events
SMC With SP+AQ
Serious events: 11 serious events
Other events: 0 other events
Deaths: 2 deaths
RTS,S/AS01
Serious events: 16 serious events
Other events: 0 other events
Deaths: 10 deaths
RTS,S/AS01 Plus SMC With SP+AQ
Serious events: 16 serious events
Other events: 0 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
SMC With SP+AQ
n=1683 participants at risk
Administration of tetanus/diphtheria toxoids vaccine followed by 4 cycles of SMC with sulphadoxine/pyrimethamine plus amodiaquine in Year 1 and 2.
Tetanus/diphtheria toxoids: One dose of tetanus/diphtheria toxoids vaccine (June) in year 1 and year 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
|
RTS,S/AS01
n=1705 participants at risk
Administration of the malaria vaccine RTS,S/AS01 followed by 4 cycles of SMC with placebo in Year 1 and 2.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
SMC placebo: Year 1 and 2 (2020/21) Four cycles of SMC placebo (July, August, September, October). In Year 2 (2021), a fifth cycle of SMC placebo was given to children in Burkina Faso in line with national guidelines.
|
RTS,S/AS01 Plus SMC With SP+AQ
n=1710 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 and 2.
SMC with SP+AQ: Year 1 and 2 (2020/21) Four cycles of SMC (SP+AQ) (July, August, September, October). One cycle of SMC consisting of sulphadoxine - pyrimethamine (SP) 500mg/25 mg, and amodiaquine (AQ) 150mg on day 1, and AQ 150mg on days 2 and 3. In Year 2 (2021), a fifth cycle of SMC with SP+AQ was given to children in Burkina Faso in line with national guidelines.
RTS,S/AS01: One booster dose of RTSS/AS01 (June) in year 1 and 2.
|
|---|---|---|---|
|
General disorders
Hospitalisations (all causes)
|
0.65%
11/1683 • Serious adverse event data were collected over a 24 month period (1st April 2020 to 31st March 2022).
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.
|
0.94%
16/1705 • Serious adverse event data were collected over a 24 month period (1st April 2020 to 31st March 2022).
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.
|
0.94%
16/1710 • Serious adverse event data were collected over a 24 month period (1st April 2020 to 31st March 2022).
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 Daniel Chandramohan
London School of Hygiene and Tropical Medicine
Phone: +447570410351
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place