Malaria Vaccine Pilot Evaluation

NCT ID: NCT03806465

Last Updated: 2024-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

30124 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-02-25

Study Completion Date

2023-07-31

Brief Summary

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The RTS,S/AS01 malaria vaccine is being introduced sub-nationally in phased pilot introductions through the EPI programmes in Malawi Ghana and Kenya. Vaccine introduction is by the respective MoH in selected areas randomly assigned to receive the vaccine at the beginning of the pilots. In the context of this programmatic activity, the Malaria Vaccine Pilot Evaluation (MVPE) registered here as observational evaluations during early vaccine introduction, include a series of 3 household surveys, and sentinel hospital and community mortality surveillance, building on routine systems.

These observational evaluations will measure:

1. The programmatic feasibility of delivering a 4 dose schedule;
2. Safety in routine use, with focus on cerebral malaria and meningitis;
3. The impact of the malaria vaccine in routine use on severe malaria and all-cause mortality

Detailed Description

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An evaluation of the pilot implementation of RTS,S/AS01 through routine health systems in moderate to high malaria transmission settings in Ghana, Kenya and Malawi. In the context of the new vaccine introduction, the Ministries of Health in the three countries will introduce the malaria vaccine (RTS,S/AS01) in a phased fashion (with some areas introducing the malaria vaccine first and the latter half, after the evaluation period) building on the national immunization programmes which routinely deliver vaccines and expanding the schedule of their routine EPI contacts.

The evaluation of the pilot implementation will run for a total of about 46 months in each country. This will focus on the three main primary objectives of feasibility, safety and impact. The pilot implementation assumes that a total of 46-60 clusters will be identified per country, evenly split between implementation and comparison areas, with each cluster contributing approximately 4,000 children per year to the evaluation of RTS,S/AS01. Hence a total of approximately 120,000 children will receive the RTS,S vaccine in each country in each year. Evaluation data will be collected in the following ways.

COMMUNITY BASED MORTALITY SURVEILLANCE

Community based mortality surveillance will be established across the pilot evaluation areas to enable the evaluation of the impact of the malaria vaccine on all-cause mortality. This will use a network of Village Reporters (VR) to document all deaths among children aged up to 48 months in the implementation and comparison areas. Once the death is notified, a standardized, WHO-approved Verbal Autopsy (VA) will be performed, according to WHO guidelines and locally acceptable practices. The VA will focus is on confirming death, age and vaccination status. The total number of clusters per country is expected to range from 46-60. Assuming 4,000 children born per cluster per year, 30 months of vaccination and a total follow-up of 44 months, each cluster will contribute 23,134 person years at risk (pyar), allowing for 1% mortality in the first month of life, and 0.08% mortality for every month after the first month. This equates to a mortality risk of 22.2 per 1000 for children aged 5 to 36 months. A mortality risk of 21 per 1,000 equates to a rate, over 2.5 years, of 8.489455 per 1,000 pyar. Based on a minimum mortality rate of 8.5 per 1000 pyar, 23 clusters in each arm, each with an annual birth cohort of approximately 4,000 subjects, would have 80% power to detect, at the 5% significance level, a decrease of at least 10% in overall mortality in each country.

With this mortality risk, the pilot evaluation it is estimated to have approximately 80% power to detect an interaction between gender and treatment of 1.15 (i.e an increased risk of mortality in girls of 1.035), compared with the 1.9-fold increase in risk among girls receiving RTS,S/AS01 in the RTS,S Phase 3 trial.

FEASIBILITY (CROSS SECTIONAL HOUSEHOLD) SURVEYS)

Three household surveys will be conducted to evaluate the programmatic feasibility to deliver a 4 dose schedule at baseline (before vaccination starts), 18 months and 30 months after start of vaccination.

A sample size of 100 houses per cluster will estimate the cluster-specific coverage of RTS,S/AS01 to within 10% (ie 95% CI from 40 to 60%) using a conservative estimate of 50% coverage and a high response rate above 95% in each cluster. Assuming a design effect of 1.5 between clusters, the overall precision in RTS,S/AS01 and coverage estimates of other vaccines over the pilot programme's implementation and comparison areas will be 2% (ie 95%CI 48% to 52%) in each country. This will result in 15,800 (6,600 in Ghana, 4,600 each in Kenya and Malawi) households included in the surveys. The second household survey may be powered to generate coverage estimates in each arm, rather than in each cluster, to within ±2% of the true value.

SENTINEL HOSPITAL SURVEILLANCE

Four to eight sentinel hospitals will be identified in each country to collect information on a larger scale on the safety of the malaria vaccine in children aged less than 5 years admitted with a focus on cases of cerebral malaria and meningitis. The catchment area of each hospital (approximately a cluster) is expected to have an annual birth cohort of, and provide services for, approximately 4,000 children in the MVPE. Hence a total catchment area of 48,000 children in implementation areas and another 48,000 children in comparison areas will contribute to the hospital-based evaluation of safety across the programme (three countries, Ghana, Kenya and Malawi). This is expected to provide 80% power to detect a 1.7-fold increase in risk of cerebral malaria and 2.6-fold increase in risk of meningitis. Children admitted to the sentinel hospitals in this age group will be assessed for severe malaria and meningitis using a standardised surveillance approach.

Conditions

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Malaria,Falciparum Feasibility Safety Mortality

Keywords

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Vaccine Malaria Africa Child

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Feasibility survey

These will be children living in the vaccinating and in non-vaccinating areas aged less than 5 years of age. For the midline household survey, this would be restricted to children aged 12-23 months of age.

Feasibility survey

Intervention Type OTHER

A survey questionnaire will be administered at each household. At the baseline household survey, each child aged less than 5 years will be tested for malaria using a rapid malaria test.

Sentinel hospital surveillance

These will be children living in the vaccinating and in non-vaccinating areas aged less than 5 years of age who are hospitalized in the 18 sentinel hospitals.

Sentinel hospital surveillance

Intervention Type OTHER

Cerebrospinal samples will be collected from all children hospitalised and suspected of having meningitis.

Community mortality surveillance

These will be children whose deaths are reported in the vaccinating and in non-vaccinating areas aged less than 5 years of age .

Community mortality surveillance

Intervention Type OTHER

A verbal autopsy will be performed

Interventions

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Feasibility survey

A survey questionnaire will be administered at each household. At the baseline household survey, each child aged less than 5 years will be tested for malaria using a rapid malaria test.

Intervention Type OTHER

Sentinel hospital surveillance

Cerebrospinal samples will be collected from all children hospitalised and suspected of having meningitis.

Intervention Type OTHER

Community mortality surveillance

A verbal autopsy will be performed

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Children aged 1-59 months

Exclusion Criteria

* Children aged less than 1 month or greater than 59 months
Minimum Eligible Age

1 Month

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Rafiq OKINE

OTHER

Sponsor Role lead

Responsible Party

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Rafiq OKINE

Medical Officer

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Don Mathanga, PhD

Role: PRINCIPAL_INVESTIGATOR

College of Medicine, Malawi

Kwaku Poku Asante, PhD

Role: PRINCIPAL_INVESTIGATOR

Kintampo Health Research Centre, Ghana

Aaron Samuels, MD

Role: PRINCIPAL_INVESTIGATOR

CDC-Kenya Malaria Program

Locations

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Kintampo Health Research Centre

Kintampo, , Ghana

Site Status

CDC Kenya Malaria Programme

Kisumu, , Kenya

Site Status

College of Medicine

Blantyre, , Malawi

Site Status

Countries

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Ghana Kenya Malawi

References

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Malaria vaccine: WHO position paper-January 2016. Wkly Epidemiol Rec. 2016 Jan 4;91(4):33-51. No abstract available. English, French.

Reference Type BACKGROUND
PMID: 26829826 (View on PubMed)

RTS,S Clinical Trials Partnership. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. 2015 Jul 4;386(9988):31-45. doi: 10.1016/S0140-6736(15)60721-8. Epub 2015 Apr 23.

Reference Type BACKGROUND
PMID: 25913272 (View on PubMed)

Hoyt J, Okello G, Bange T, Kariuki S, Jalloh MF, Webster J, Hill J. RTS,S/AS01 malaria vaccine pilot implementation in western Kenya: a qualitative longitudinal study to understand immunisation barriers and optimise uptake. BMC Public Health. 2023 Nov 18;23(1):2283. doi: 10.1186/s12889-023-17194-2.

Reference Type DERIVED
PMID: 37980467 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.who.int/docs/default-source/immunization/mvip/mvip-milestones-to-programme-development-final.pdf?Status=Temp&sfvrsn=14768db0_2

Key milestones in the development of the Malaria Vaccine Implementation Programme (MVIP): from pilot recommendation to vaccine introduction

Other Identifiers

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RTSS MVPE

Identifier Type: -

Identifier Source: org_study_id