Post-discharge Malaria Chemoprevention(PMC) Study

Liverpool School of Tropical Medicine

Status and phase

Completed

Phase 3

Conditions

Severe Anemia

Malaria

Treatments

Drug: dihydroartemisinin-piperaquine placebo

Drug: dihydroartemisinin-piperaquine

Study type

Interventional

Funder types

Other

Identifiers

NCT02671175

2015-125 (Other Identifier)

2965 (Other Identifier)

2014/1911 (Other Identifier)

14.034

Details and patient eligibility

About

This study evaluates the efficacy and safety of 3 months of malaria chemoprevention post-discharge using dihydroartemisinin piperaquine (DHA-P) in children under 5 years of age admitted with severe anemia. One half will receive monthly DHA-P and the other half placebo.

Full description

Children hospitalized with severe anemia in Africa are at high risk of readmission or death within 6 months after discharge. No strategy specifically addresses this post-discharge period. In Malawi, 3 months of post-discharge malaria chemoprevention with monthly 3-day treatment courses of artemether-lumefantrine (AL) in children with severe malarial anemia prevented 31% of deaths and readmissions. This study is a confirmatory efficacy trial in Kenya and Uganda to determine the efficacy and safety of malaria chemoprevention post-discharge. We hypothesize that an additional three months of malaria chemoprevention with monthly 3-day treatment courses with DHA-piperaquine (each providing about 4 weeks of post-treatment prophylaxis) provided during the post-discharge period to children recently admitted with severe anemia is superior to reduce all-cause readmission and mortality rates by 6 months compared with 2 weeks of post-treatment prophylaxis provided by the single course of oral AL when given as part of the standard in-hospital care around the time of discharge.

Enrollment

1,049 patients

Sex

All

Ages

Under 60 months old

Volunteers

No Healthy Volunteers

Inclusion criteria

Pre-study screening
1. Haemoglobin <5.0 g/dl or PCV < 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital
2. Aged less than 59.5 months
3. Body weight >5 kg
4. Resident in catchment area Enrolment in study(t=0)

1. Fulfilled the pre-study screening eligibility criteria
2. Aged < 59.5 months
3. Clinically stable, able to take oral medication
4. Subject completed blood transfusion(s) or became clinically stable without transfusion
5. Able to feed (for breastfeeding children) or eat (for older children)
6. Absence of know cardiac problems
7. Provision of informed consent by parent or guardian Randomisation (t=2 weeks)

1. Fulfilled enrolment eligibility criteria and was enrolled during recent admission
2. Aged <60 months
3. Still clinically stable, able to take to oral medication, able to feed (for breastfeeding children) or eat (for older children) and able to sit unaided (for older children who were already able to do so prior to hospitalisation)

Exclusion criteria

Pre-study screening
1. Recognised specific other cause of severe anaemia (e.g. trauma, haematological malignancy, known bleeding disorder)
2. Known sickle cell disease
3. Anticipated to reach the 5th birthday (60 months of age) within 2 weeks from enrolment (i.e. prior to randomization)
4. Child will reside for more than 25%of the 6 months study period (i.e. 6 weeks or more) outside of catchment area Enrolment in study (t=0)

1. Previous enrolment in the present study
2. Known hypersensitivity to study drug
3. Sickle cell disease
4. Use or known need at the time of enrolment for concomitant prohibited medication during the 14 weeks PMC treatment period.
5. Ongoing or planned participation in another clinical trial involving ongoing or scheduled treatment with prohibited medicinal products or active follow-up during the course of the study (6 months from enrolment)
6. A known need at the time of enrolment for scheduled surgery during the subsequent course of the study (6 months from enrolment)
7. Suspected non-compliance with the follow-up schedule
8. Know heart conditions, or family history of congenital prolongation of the QTc interval.
9. Taking medicinal products that are known to prolong the QTc interval Randomisation (t=2 weeks)

1. Used dihydroartemisinin since enrolment
2. Use or known need at the time of randomisation for concomitant prohibited medication during the 14 weeks PMC treatment period.
3. Enrolled, or known agreement to enrol into another clinical trial involving ongoing or scheduled treatment with medicinal products during the course of the study (6 months from enrolment)
4. A known need at the time of randomisation for scheduled surgery during the subsequent course of the study (6 months from enrolment)
5. Suspected non-compliance with the follow-up schedule
6. Withdrawal of consent since enrolment