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

NCT03178643 | Completed Phase 4 Results DMC

• 2 other identifiers: Pro00077428R01HL134211
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (1)

• Incidence of Clinical Malaria Per Patient Year

  The primary endpoint is the cumulative incidence of clinical malaria expressed as episodes per person-year at risk. Time at risk will begin when study participants are randomized and receive study drug (i.e. begin chemoprevention) and end when participants reach the end of the observation period.

  12 months

Secondary Outcomes (14)

• Number of Participants With Severe Anemia

  12 months

• Number of Participants With Severe Malaria

  12 months

• Number of Participants With Hospitalization for Malaria

  12 months

• Number of Participants With Light Microscopy (LM)-Positive Malaria

  12 months

• Number of Participants With Unconfirmed Malaria

  12 months

Study Arms (3)

Proguanil Oral Tablet

ACTIVE COMPARATOR

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

Sulfadoxine/Pyrimethanine-Amodiaquine

ACTIVE COMPARATOR

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)

Dihydroartemisinin-Piperaquine (DP)

ACTIVE COMPARATOR

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)

Interventions

Proguanil Oral Tablet DRUG

Dosing of daily proguanil will be approximately 3mg/kg/day,

Proguanil Oral Tablet

Sulfadoxine/Pyrimethanine-Amodiaquine (SP-AQ) DRUG

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

Sulfadoxine/Pyrimethanine-Amodiaquine

Dihydroartemisinin-Piperaquine (DP) DRUG

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

Dihydroartemisinin-Piperaquine (DP)

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Homa Bay County Referral Hospital

Homa Bay Town, Homa Bay County, 40300, Kenya

Location

Related Publications (1)

• Taylor SM, Korwa S, Wu A, Green CL, Freedman B, Clapp S, Kirui JK, O'Meara WP, Njuguna FM. Monthly sulfadoxine/pyrimethamine-amodiaquine or dihydroartemisinin-piperaquine as malaria chemoprevention in young Kenyan children with sickle cell anemia: A randomized controlled trial. PLoS Med. 2022 Oct 10;19(10):e1004104. doi: 10.1371/journal.pmed.1004104. eCollection 2022 Oct.

  PMID: 36215323 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Proguanil; Sulfadoxine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Benzenesulfonamides; Sulfonamides; Amides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Dr. Steve Taylor
• Organization: DCRI

steve.taylor@duke.edu

9198245232

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 7, 2017
• Study Start: January 23, 2018
• Primary Completion: December 16, 2020
• Study Completion: December 16, 2020
• Last Updated: April 23, 2024
• Results First Posted: March 27, 2024

Record last verified: 2024-04

Locations

KE (1)