Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE)
Condition: Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum; Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a randomized, three-arm, open-label, clinical trial of malaria chemoprevention in
      children with sickle-cell anemia (SCA) at a single site in Homa Bay, Kenya. The study will
      enroll 246 children under 10 years of age, randomize participants 1:1:1 to one of three
      malaria chemoprevention regimens, and follow participants monthly for 12 months in order to
      record clinical episodes of malaria or SCA-related morbidity. Analyses will compare the
      efficacy of each regimen to prevent malaria and SCA morbidity.
    

Detailed description: 
      Purpose of the study:

      Primary Objective: To compare the efficacy of daily proguanil with monthly
      sulfadoxine/pyrimethanine-amodiaquine (SP-AQ) and with monthly dihydroartemisinin-piperaquine
      (DP) on the incidence of falciparum malaria in children with SCA.

      Secondary Objective: To compare the efficacy of these malaria chemoprevention strategies on
      the incidence of major complications of SCA.

      Background & significance

      Over 240,000 children with sickle cell anemia (SCA) are born in Africa annually. This number
      will increase to over 350,000 annual births of children with SCA by the year 2050. Without
      sophisticated medical care, SCA patients in African settings die at young ages: in a Western
      Kenya cohort of newborns, 25% of SCA children died before their 3rd birthday. Caring
      effectively for these children will be a major challenge for developing medical and public
      health systems in Africa including Kenya, and modeling studies suggest that the adequate
      provision of effective preventive care can substantially reduce the mortality of these
      children. Preventive care for SCA children must be evidence-based and tailored to the unique
      epidemiology of comorbidities in African settings.

      Children under 5 years of age in sub-Saharan Africa also suffer the majority of the annual
      350 million infections and 500,000 deaths globally. Reducing this burden is a global public
      health priority, particularly in areas of high transmission like Western Kenya. In the
      absence of an effective vaccine, global malaria control requires effective treatments and a
      suite of preventive measures that act upon the parasite, environment, and host. Among these
      preventive strategies is the administration of prophylactic antimalarials to high risk
      groups, including pregnant women, infants, and children exposed to seasonal malaria
      transmission. In these high-risk groups malaria morbidity is substantially reduced by routine
      periodic intake of effective antimalarials.

      Children with SCA are at high risk of life-threatening malaria. In East Africa children with
      SCA admitted to the hospital with malaria parasites were more likely to die than those
      without parasites. Malaria is also a precipitant of sickle-cell pain crises, by unclear
      mechanisms. It remains unclear how SCA influences the overall risk of malaria, because most
      studies have been hospital based and therefore unsuited to capture mild episodes. The twin
      observations that malaria is more severe in SCA children and precipitates painful crises in
      these children indicate that the prevention of P. falciparum infections is critical to
      prolong the survival of SCA children in malaria-endemic areas.

      Design & procedures - This is a randomized, three-arm, open-label, clinical trial of malaria
      chemoprevention in children with sickle-cell anemia (SCA) at a single site in Homa Bay,
      Kenya. The study will enroll 246 children under 10 years of age, randomize participants 1:1:1
      to one of three malaria chemoprevention regimens, and follow participants monthly for 12
      months in order to record clinical episodes of malaria or SCA-related morbidity. Analyses
      will compare the efficacy of each regimen to prevent malaria and SCA morbidity.
    

Intervention name(s): Proguanil Oral Tablet; Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ); Dihydroartemisinin-Piperaquine (DP)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Dosing of daily proguanil will be approximately 3mg/kg/day,; Age 1-5 on Day 1: One tablet 500/25mg SP and one tablet 153mg AQ Day 2 and Day 3: one tablet 153 mg AQ only each day For ages 6-10: Day 1 - 1.5 tablets 500/25mg SP and 1.5 tablets 153mg AQ Days 2 and 3: 1.5 tablets 153mg AQ only each day; 3) The weight-based dosing of tablets of 40/320mg of DP is described below:
Weight (kg) No. of 40/320mg tabs DP daily for 3 days
≤ 5 ¼ 6-10 ½ 11-14 ¾ 15-19 1 20-23 1 ¼ 24-25 1 ½
Intervention MeSH terms: Piperaquine; Sulfadoxine; Amodiaquine; Artenimol; Proguanil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention