Seasonal Malaria Chemoprevention With Dihydroartemisin Piperaquin vs. Sulfadoxine-pyrimethamin+Amodiaquin

NCT04149106 | Unknown Phase 3 DMC

• 1 other identifier: 17-0052
• Study Type: interventional
• Target: 4,556
• Locations: 1 country
• Sites: 1

Brief Summary

Seasonal Malaria Chemoprevention (SMC) for children less than five years old is one the high impact interventions against malaria in sub-Saharan Africa (SSA). Since 2016, the Government of Mali and partners through the National Malaria Control Program has deployed SMC countrywide during high malaria transmission season with a total of four (4) rounds per year. Sulfadoxine-Pyrimethamine (SP) with Amodiaquine (AQ) are the drugs used for SMC. However, SP is also used for Intermittent preventative treatment (IPTp) for pregnant women while AQ has been used for decades for treatment of uncomplicated malaria. The proposed study will examine the effect of SMC with Sulfadoxine+Amodiaquine (SP+AQ) extension to older age, the efficacy of Dihydroartemisin-Piperaquine (DHA-PQ) when used for SMC, social, cultural, economic and health systems factors associated with effective implementation of SMC. The specific aims of this study are to: 1\] Assess the effect of SMC (SP+AQ) on malaria incidence and infection prevalence in different age groups across sites; 2\] Study the effect of SMC (DHA-PQ) compared to SMC (SP-AQ) among children less than 10 years; 3\] Determine the cost-effectiveness for each treatment regimen; ) 4\] Explore factors determining effective SMC implementation including coverage of children targeted to receive treatment by community distributors, receipt of a full course of treatment, perception of medications by parents and health care providers, and sustainability; and 5) Establish a district based system to identify severe cases. The expected outcomes of this work, upon completion of our specific aims, include 1) Recommendations to Malian health officials and other partners for improving implementation of SMC and alternative drug to SP+AQ for SMC, and 2) Guidelines for routine monitoring of SMC implementation.

Conditions

Malaria,Falciparum

Keywords

SMC; Effectiveness; SPAQ; DHAPQ; Drug resistance

Outcome Measures

Primary Outcomes (1)

• Malaria incidence among cohort in 2 years period

  The incidence of malaria (uncomplicated or severe malaria): Uncomplicated malaria being defined as symptomatic malaria parasitaemia with no signs of severity and/or evidence of vital organ dysfunction measured by: (1) rapid diagnostic tests and/or (2) microscopy of blood smears. Severe malaria is defined as confirmed malaria parasitemia plus fever or history of fever (at least 37°C) plus evidence of severe/complicated pathology; e.g., convulsions, vomiting, coma, rapid (kussumal) breathing or evidence of vital organ dysfunction, and severe anemia.

  2 years

Secondary Outcomes (3)

• Malaria infection prevalence at the start and the end of malaria transmission season

  2 years

• Drug resistance marker prevalence in two 2 years period

  1 year

• SMC coverage and treatment compliance during malaria transmission season

  2 years

Other Outcomes (1)

• Malaria control tools usage in communities

  2 years

Study Arms (3)

Standard

ACTIVE COMPARATOR

The Mali National Malaria Control program has initiated SMC for children less than 5 years since 2016 (countrywide) with SPAQ. This standard care will not change in this arm

Drug: Sulfadoxine pyrimethamine + Amodiaquin

SMC with SPAQ extended to older children

ACTIVE COMPARATOR

Within this arm, SMC with SPAQ will be extended to children 5-9 years old

Drug: Sulfadoxine pyrimethamine + Amodiaquin

SMC with DHAPQ

ACTIVE COMPARATOR

Children less than 10 years within this arm will received Dihydroartemisin piperaquin for SMC instead of SPAQ

Drug: Dihydroartemisinin piperaquin

Interventions

Sulfadoxine pyrimethamine + Amodiaquin DRUG

Monthly dose of SPAQ over three days for SMC

Also known as: SPAQ

SMC with SPAQ extended to older children; Standard

Dihydroartemisinin piperaquin DRUG

Monthly dose of DHAPQ for SMC

Also known as: DHAPQ

SMC with DHAPQ

Eligibility Criteria

• Age: 3 Months - 119 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Village resident (up to the end of the malaria transmission season)
• Age 3 months to 119 month age at the time of enrollment
• Parent or guardian provided consent for their child's participant (5-14 years old)
• Absence of chronic diseases, history of allergy to SP, AQ or DHA-PQ

You may not qualify if:

• Non resident
• Age less than 3months or greater or equal to 119 months at the time of cohort enrollment
• Presence of chronic diseases, history of allergy to SP, AQ or DHA-PQ
• Does not provide consent/assent required according to age to participate in the study

Sponsors & Collaborators

• University Clinical Research Center, Mali: lead
• Tulane University: collaborator
• University of South Florida: collaborator
• University of Copenhagen: collaborator
• Deakin University: collaborator
• Johns Hopkins University: collaborator

Study Sites (1)

Ucrc - Usttb

Bamako, Select, B.P. 5445, Mali

Location

Related Publications (7)

• Chotsiri P, Zongo I, Milligan P, Compaore YD, Some AF, Chandramohan D, Hanpithakpong W, Nosten F, Greenwood B, Rosenthal PJ, White NJ, Ouedraogo JB, Tarning J. Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children. Nat Commun. 2019 Jan 29;10(1):480. doi: 10.1038/s41467-019-08297-9.

  PMID: 30696903 BACKGROUND

• Zongo I, Milligan P, Compaore YD, Some AF, Greenwood B, Tarning J, Rosenthal PJ, Sutherland C, Nosten F, Ouedraogo JB. Randomized Noninferiority Trial of Dihydroartemisinin-Piperaquine Compared with Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention in Burkina Faso. Antimicrob Agents Chemother. 2015 Aug;59(8):4387-96. doi: 10.1128/AAC.04923-14. Epub 2015 Apr 27.

  PMID: 25918149 BACKGROUND

• Some AF, Zongo I, Compaore YD, Sakande S, Nosten F, Ouedraogo JB, Rosenthal PJ. Selection of drug resistance-mediating Plasmodium falciparum genetic polymorphisms by seasonal malaria chemoprevention in Burkina Faso. Antimicrob Agents Chemother. 2014 Jul;58(7):3660-5. doi: 10.1128/AAC.02406-14. Epub 2014 Apr 14.

  PMID: 24733476 BACKGROUND

• Maiga H, Lasry E, Diarra M, Sagara I, Bamadio A, Traore A, Coumare S, Bahonan S, Sangare B, Dicko Y, Diallo N, Tembely A, Traore D, Niangaly H, Dao F, Haidara A, Dicko A, Doumbo OK, Djimde AA. Seasonal Malaria Chemoprevention with Sulphadoxine-Pyrimethamine and Amodiaquine Selects Pfdhfr-dhps Quintuple Mutant Genotype in Mali. PLoS One. 2016 Sep 23;11(9):e0162718. doi: 10.1371/journal.pone.0162718. eCollection 2016.

  PMID: 27662368 BACKGROUND

• Dicko I, Konate D, Diakite SAS, Keita B, Sanogo I, Fomba A, Traore A, Kone J, Kante S, Tessougue O, Diawara SI, Doumbia S, Diakite M. Relationship between red blood cell polymorphisms and effectiveness of seasonal malaria chemoprevention in 2020 in Dangassa, Mali. Parasitol Res. 2024 Oct 14;123(10):350. doi: 10.1007/s00436-024-08372-1.

  PMID: 39400721 DERIVED

• Toure M, Shaffer JG, Sanogo D, Keita S, Keita M, Kane F, Traore B, Dabitao D, Kone A, Doumbia CO, Keating J, Yukich J, Hansson HH, Barry AE, Diakite M, Alifrangis M, Doumbia S. Seasonal Malaria Chemoprevention Therapy in Children Up To 9 Years of Age: Protocol for a Cluster-Randomized Trial Study. JMIR Res Protoc. 2024 Jan 22;13:e51660. doi: 10.2196/51660.

  PMID: 38252481 DERIVED

• Konate D, Diawara SI, Keita B, Sogoba N, Fayical M, Guindo A, Thiam S, Traore SF, Shaffer JG, Doumbia S, Diakite M. Effectiveness and Community Acceptance of Extending Seasonal Malaria Chemoprevention to Children 5 to 14 Years of Age in Dangassa, Mali. Am J Trop Med Hyg. 2021 Nov 15;106(2):648-654. doi: 10.4269/ajtmh.21-0046.

  PMID: 34781256 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

fanasil, pyrimethamine drug combination; Amodiaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Seydou Doumbia, PhD

  University Clinical Research Center - USTTB - Mali

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Any
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A cluster randomized design will be used. Year 1: Arm 1: SPAQ for children less than 10 years old (Standard treatment) Arm2: SPAQ will be delivery to children 3 months to less than 10 years (extension of SMC to children 5-9 years with current drug) Arm 3: DHAPQ will be delivery to children 3 months to less than 10 years Year 2: Arm 1: SPAQ will be delivery to children 3 months to less than 10 years (extension of SMC to children 5-9 years with current drug) Arm2: DHAPQ will be delivery to children 3 months to less than 10 years Arm 3: Standard of care defined as SPAQ for children less than 5 years old according the NMCP national politic for malaria control

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: November 4, 2019
• Study Start: July 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 30, 2023
• Last Updated: March 7, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: All data and resources will be made available as soon as possible but no later than within one year of the completion of the funded project period (2021) or upon acceptance of the data for publication, or public disclosure of a submitted patent application, whichever is earlier.
• Access Criteria: we will identify where the data will be available and how to access the data in any publications and presentations that we author or co-author about these data, as well as acknowledge the repository and funding source in any publications and presentations. All repositories mentioned have policies and procedures in place that will provide data access to qualified researchers or registered users, fully consistent with NIH data sharing policies and applicable laws and regulations.

Locations

MA (1)