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Phase 4 N=246 Randomized Prevention

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

Malaria,Falciparum

Enrolled (actual)
246
Serious AEs
25.6%
Results posted
Mar 2024
Primary outcome: Primary: Incidence of Clinical Malaria Per Patient Year — 0.04; 3.05; 1.36 episodes/patient year

Study Design & Population

Study type
Interventional
Phase
Phase 4
Interventions
Proguanil Oral Tablet (Drug); Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) (Drug); Dihydroartemisinin-Piperaquine (DP) (Drug)
Age
Pediatric · 1+ yrs
Sex
All
Sponsor
Duke University
Primary completion
Dec 2020

Outcome Measures

OutcomeResultp-value
PRIMARY
Incidence of Clinical Malaria Per Patient Year
0.04; 3.05; 1.36
SECONDARY
Number of Participants With Severe Anemia
8; 9; 4
SECONDARY
Number of Participants With Severe Malaria
0; 0; 0
SECONDARY
Number of Participants With Hospitalization for Malaria
3; 3; 3
SECONDARY
Number of Participants With Light Microscopy (LM)-Positive Malaria
17; 11; 19
SECONDARY
Number of Participants With Unconfirmed Malaria
42; 25; 40
SECONDARY
Number of Participants With Fatal Malaria
0; 0; 0
SECONDARY
Number of Participants With Asymptomatic Parasitization
45; 20; 9
SECONDARY
Number of Participants With Painful Events
33; 28; 30
SECONDARY
Number of Participants With Dactylitis
81; 57; 37
SECONDARY
Number of Participants With Transfusions
13; 7; 4
SECONDARY
Number of Participants With Acute Chest Syndrome
1; 3; 0
SECONDARY
Number of Participants With All-cause Hospitalization
47; 52; 40
SECONDARY
All-cause Deaths
2; 7; 1
SECONDARY
Molecular Markers of Malaria Parasite Drug Resistance

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.

Eligibility 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03178643). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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