Mass Vaccine and Drug Administration, Bangladesh
ConditionPlasmodium Falciparum Malaria
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age6+
SponsorUniversity of Oxford
About this trial
This is an open i.e. not blinded, cluster-randomised, controlled intervention study. The study will use a factorial design to estimate the protective effectiveness of mass drug administrations, mass vaccinations, combined mass vaccinations and drug administrations versus the current standard of care.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Current residence in a study village irrespective of permanence
Age 6 months and above (no upper age limit)
Written informed consent provided by participants (or a parent/guardian in case the participant is under 18 years old)
Disqualifiers
Pregnancy, plan to get pregnant, or breastfeeding.
Acute illness requiring intervention
A history of an adverse reaction to study drugs/vaccine and prior receipt of any other malaria vaccine or enrolment in another intervention trial.
Trial design
Design model
Parallel
Treatments tested in this trial
DHA/piperaquine and a SLD-PQ
DrugParticipants in Arms 1 and 2 will receive three rounds of antimalarial drugs - each round starting on the day of vaccination (Day 0) at Study Months 0, 1, and 2. Each round consists of three daily doses of co-formulated dihydroartemisinin/piperaquine on Day 0, 1, and 2 (i.e. the day of vaccination and each day for 2 days after). The drug dose is based on the weight of the participant at the first visit (M0D0). Dihydroartemisinin/piperaquine tablets (Shanghai Fosun Pharmaceutical Co., Ltd.) for adult participants each contain 40 mg dihydroartemisinin and 320 mg piperaquine with a therapeutic dose range between 2-10 mg/kg/day dihydroartemisinin and 16-26 mg/kg/dose piperaquine. In addition, each participant will receive a single low dose primaquine on the day of vaccination (Day 0; Table 4). One single low dose primaquine of approximately 0.25 mg/kg (Thai Government Pharmaceutical Organisation) will be administered. Children under 10kg do not receive PQ.
Study vaccine R21/Matrix-M™
Biological/VaccineThe mixing prior to administration strategy will involve withdrawal of 0.5 mL antigen from one vial of R21 Malaria vaccine and adding it to Matrix-M1 vial. 0.5 mL of R21 antigen shall be withdrawn from another vial of R21 Malaria vaccine and be added to the same Matrix-M1 vial. The total volume in Matrix-M1 vial will be 1.5 mL. After addition the content will be mixed gently, and 0.75 mL of the mixture will be withdrawn and administered to participants. Each dose of 0.75mL (after mixing of R21 with Matrix-M1) will contain 10 µg of R21 and 50 µg for participants 14 years and older. In children up to 14 years a 5 μg will be used.
Treatment groups
10,000 Participants
are divided into 4 treatment groupsGroup A: MDA + VaccineActive comparator 2 interventions
Group B: MDA onlyActive comparator 1 intervention
Group C: Vaccine onlyActive comparator 1 intervention
Group D: ControlNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
Falciparum malaria incidence by study groups
Falciparum malaria incidence will be determined by the number of clinical falciparum malaria cases confirmed by Rapid diagnostic test (RDT) or microscopy to determine the overall protective efficacy against clinical falciparum malaria among study groups. The investigators will look for the presence of axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy as a primary case definition of clinical falciparum malaria.
Time frame
Data will be collected for two years following baseline intervention (Month 0 to Month 24)2
Falciparum malaria prevalence by study groups
Falciparum malaria prevalence will be determined by the number of positive falciparum confirmed by dried blood spots (DBS) polymerase chain reaction (PCR) malaria detection method during cross-sectional surveys to determine the overall protective efficacy against subclinical P. falciparum among study groups. * The investigators will collect dried blood spots to detect malaria during cross-sectional surveys from the healthy participants. * Those who have axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy will receive treatment according to national treatment guidelines.
Time frame
PCR for malaria detection from DBS will be collected at 6th month intervals until two years following baseline intervention (Month 0, Month 6, Month 12, Month 18 and Month 24)3
Overall percentage of falciparum malaria positivity by study groups
The percentage of falciparum malaria positivity will be determined by the number of falciparum positives detected by PCR, RDT or microscopy to determine overall protective efficacy against clinical and subclinical falciparum malaria among study groups. Dried blood spots to detect malaria from by PCR will be collected at baseline and every six months until two years. Clinical malaria data detected by rapid diagnostic test or microscopy will be collected for two years following intervention. * The investigators will look for the presence of axillary temperature ≥37.5°C AND P. falciparum positive RDT or microscopy as a primary case definition of clinical malaria. * The investigators will collect dried blood spots to detect malaria during cross-sectional surveys from the healthy participants.
Time frame
DBS: Month 0, Month 6, Month 12, Month 18 and Month 24 and Clinical malaria data for two year following interventionSecondary outcomes
1
The incidence of Deaths related to falciparum malaria among study groups
The number of Deaths related to falciparum malaria (confirmed by RDT or microscopy) will be recorded for two year following intervention. Death rate among study groups will be compared
Time frame
Data will be collected for two years following baseline intervention (Month 0 to Month 24)2
The incidence of severe malaria disease among study groups
The number of Severe malaria diseases (according to WHO criteria) will be recorded for two years following intervention and the incidences will be compared among study groups. Primary case definition of severe malaria: * Presence of P. falciparum (RDT positive or microscopy positive); AND one of more of the following criteria of disease severity: * Prostration * Respiratory distress * Blantyre coma score ≤ 3 * Seizures: 2 or more * Hypoglycemia \< 2.2 mmol/L * Acidosis BE ≤-8.0 mmol/L * Lactate ≥ 5.0 mmol/L * Anemia \< 5.0 g/dL * Acute kidney injury * Pulmonary oedema * Significant bleeding * Shock (systolic BP \<70mm Hg); AND Without any of the following criteria of co- morbidity * Pneumonia (confirmed by X-ray) * Meningitis (confirmed by CSF examination) * Sepsis (with Positive blood culture) * Gastroenteritis with dehydration
Time frame
Data will be collected for two years following baseline intervention (Month 0 to Month 24)3
The incidence of severe anaemia among study groups
The number of severe anemia cases will be recorded for two years following interventions among all participants and the proportions will be compared among study groups Severe anaemia due to severe malaria according to WHO criteria * Anaemia \< 5.0 g/dL * Requires blood transfusion according to National guidelines
Time frame
Data will be collected for two years following baseline intervention (Month 0 to Month 24)4
Vivax malaria incidence by study groups
Vivax malaria incidence will be determined by the number of clinical vivax malaria cases confirmed by RDT or microscopy to determine the overall protective efficacy against clinical vivax malaria among study groups. The investigators will look for the presence of axillary temperature ≥37.5°C AND P.vivax positive RDT or microscopy as a primary case definition of clinical vivax malaria.
Time frame
Data will be collected for two years following baseline intervention (Month 0 to Month 24)Sponsors and contacts
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Source ClinicalTrials.gov