Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE) (EPiTOMISE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03178643|
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : June 6, 2018
|Condition or disease||Intervention/treatment||Phase|
|Malaria,Falciparum||Drug: Proguanil Oral Tablet Drug: Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) Drug: Dihydroartemisinin-Piperaquine (DP)||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||246 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE)|
|Actual Study Start Date :||January 23, 2018|
|Estimated Primary Completion Date :||October 2019|
|Estimated Study Completion Date :||October 2019|
Active Comparator: Proguanil Oral Tablet
Proguanil is the current standard of care for chemoprevention of malaria in children with SCA in Kenya. This medication will be taken on a daily basis
Drug: Proguanil Oral Tablet
Dosing of daily proguanil will be approximately 3mg/kg/day,
Active Comparator: Sulfadoxine/Pyrimethanine-Amodiaquine
Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) is a combination therapy comprised of sulfadoxine and pyrimethamine (two antifolate antimicrobials) co-administered with amodiaquine. This medication is taken on a monthly basis.
Drug: Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ)
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
Active Comparator: Dihydroartemisinin-Piperaquine (DP)
DP is an artemisinin-combination therapy consisting of the artemisinin derivative dihydroartemisinin and the bisquinoline piperaquine. This medication is taken on a monthly basis.
Drug: Dihydroartemisinin-Piperaquine (DP)
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
- Incidence of malaria over 12 months. [ Time Frame: 12 months ]as above
- Incidence of SCA-related morbidity [ Time Frame: 12 months ]E.g., pain crises, transfusions, acute chest syndrome, all-cause hospitalization or deaths, severe malaria, drug-resistant malaria parasites
- Severe malaria [ Time Frame: 12 months ]Rapid diagnostic testing
- Hospitalization for malaria [ Time Frame: 12 months ]Patient admitted to hospital for malaria
- LM-positive malaria [ Time Frame: 12 months ]Rapid diagnostic testing
- Unconfirmed malaria [ Time Frame: 12 months ]Receipt of antimalarials unconfirmed by any diagnostic test
- Fatal malaria [ Time Frame: 12 months ]If cause of death is malaria
- Asymptomatic parasitization [ Time Frame: 12 months ]blood smear providing parasite composition that is malaria, but patient shows no malaria symptoms
- Painful events [ Time Frame: 12 months ]Events described by patient or parents consistent with sickle cell anemia pain crisis
- Dactylitis [ Time Frame: 12 months ]clinical assessment
- Transfusions [ Time Frame: 12 months ]The number of transfusions required per patient
- Acute chest syndrome [ Time Frame: 12 months ]clinical assessment and patient or parent description
- All-cause hospitalization [ Time Frame: 12 months ]admitted to hospital
- All-cause deaths [ Time Frame: 12 months ]death
- Molecular markers of malaria parasite drug resistance [ Time Frame: 12 months ]blood samples tested for drug resistance
- First Composite Outcome [ Time Frame: 12 months ]outcome of dactylitis or painful event will be compared between arms
- Second Composite Outcome [ Time Frame: 12 months ]receipt of blood products, ACS, hospitalization, or death will be compared between arms
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03178643
|Contact: Steve Taylor, MD||919 email@example.com|
|Contact: Sheila P Clapp, MBA||919 firstname.lastname@example.org|
|Homa Bay County Referral Hospital||Recruiting|
|Homa Bay Town, Homa Bay County, Kenya, 40300|
|Contact: Sarah Korwa, Nursing +254719474231 email@example.com|
|Contact: Joseph Kipkoech +254719474231 firstname.lastname@example.org|
|Principal Investigator: Festus Njuguna, MMedPed|