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Trial record 16 of 42 for:    sickle cell anemia OR sickle cell disease OR hemoglobin S disease OR hemoglobin SS disease | Recruiting, Not yet recruiting, Available Studies | NIH, U.S. Fed

Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE) (EPiTOMISE)

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ClinicalTrials.gov Identifier: NCT03178643
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : June 6, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Duke University

Brief 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.

Condition or disease Intervention/treatment Phase
Malaria,Falciparum Drug: Proguanil Oral Tablet Drug: Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) Drug: Dihydroartemisinin-Piperaquine (DP) Phase 4

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 246 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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


Arm Intervention/treatment
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





Primary Outcome Measures :
  1. Incidence of malaria over 12 months. [ Time Frame: 12 months ]
    as above


Secondary Outcome Measures :
  1. 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

  2. Severe malaria [ Time Frame: 12 months ]
    Rapid diagnostic testing

  3. Hospitalization for malaria [ Time Frame: 12 months ]
    Patient admitted to hospital for malaria

  4. LM-positive malaria [ Time Frame: 12 months ]
    Rapid diagnostic testing

  5. Unconfirmed malaria [ Time Frame: 12 months ]
    Receipt of antimalarials unconfirmed by any diagnostic test

  6. Fatal malaria [ Time Frame: 12 months ]
    If cause of death is malaria

  7. Asymptomatic parasitization [ Time Frame: 12 months ]
    blood smear providing parasite composition that is malaria, but patient shows no malaria symptoms

  8. Painful events [ Time Frame: 12 months ]
    Events described by patient or parents consistent with sickle cell anemia pain crisis

  9. Dactylitis [ Time Frame: 12 months ]
    clinical assessment

  10. Transfusions [ Time Frame: 12 months ]
    The number of transfusions required per patient

  11. Acute chest syndrome [ Time Frame: 12 months ]
    clinical assessment and patient or parent description

  12. All-cause hospitalization [ Time Frame: 12 months ]
    admitted to hospital

  13. All-cause deaths [ Time Frame: 12 months ]
    death

  14. Molecular markers of malaria parasite drug resistance [ Time Frame: 12 months ]
    blood samples tested for drug resistance

  15. First Composite Outcome [ Time Frame: 12 months ]
    outcome of dactylitis or painful event will be compared between arms

  16. Second Composite Outcome [ Time Frame: 12 months ]
    receipt of blood products, ACS, hospitalization, or death will be compared between arms



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than 12 months and less than 10 years at enrollment;
  • Current attendance at or willingness to attend the study SCA clinic at HBCH;
  • Residence in either Homa Bay County or the Rongo or Awendo sub-counties of Migori County;
  • Confirmed hemoglobin genotype of HbSS by electrophoresis, HPLC, or PCR;
  • No immediate, apparent, or reported plans to relocate residence from Homa Bay County or the Rongo or Awendo sub-counties of Migori County in the next 2 years;
  • Ability to take oral medication and be willing to adhere to the medication regimen or caregiver willingness to give the medical regimen as prescribed;
  • Ability and willingness of parent or legally authorized representative (LAR) to give informed consent;
  • Assent of child in those > 7 years.

Exclusion Criteria:

  • Taking routine antimalarial prophylaxis for another indication (including co-trimoxazole for HIV infection);
  • Temperature of ≥ 37.5C at screening or history of objective or subjective fever in the preceding 24 hours during screening;
  • Known allergy or sensitivity to sulfadoxine, pyrimethamine, amodiaquine, proguanil, dihydroartemisinin, piperaquine, artemether, lumefantrine, pencillin (if under 5 years old), or derivatives of these compounds;
  • Known chronic medical condition other than SCA (i.e. malignancy, HIV) requiring frequent medical attention;
  • Currently participating in another clinical research study, or having participated in one in the prior 30 days;
  • Living in the same household as a previously-enrolled study participant;
  • Chronic use of medications known to prolong the QT interval in children (see Appendix J);
  • Fridericia's corrected QT interval (QTcF) interval > 450msec.

Information from the National Library of Medicine

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


Contacts
Contact: Steve Taylor, MD 919 684-5815 steve.taylor@duke.edu
Contact: Sheila P Clapp, MBA 919 338-6777 sheila.clapp@duke.edu

Locations
Kenya
Homa Bay County Referral Hospital Recruiting
Homa Bay Town, Homa Bay County, Kenya, 40300
Contact: Sarah Korwa, Nursing    +254719474231    sarahkorwa@gmail.com   
Contact: Joseph Kipkoech    +254719474231    josepheddykipkoech@gmail.com   
Principal Investigator: Festus Njuguna, MMedPed         
Sponsors and Collaborators
Duke University
National Heart, Lung, and Blood Institute (NHLBI)

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03178643     History of Changes
Other Study ID Numbers: Pro00077428
R01HL134211 ( U.S. NIH Grant/Contract )
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: June 6, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Anemia, Sickle Cell
Parasitic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Malaria
Malaria, Falciparum
Protozoan Infections
Hemoglobinopathies
Piperaquine
Sulfadoxine
Amodiaquine
Dihydroartemisinin
Artemisinins
Proguanil
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Anti-Infective Agents, Urinary
Renal Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action