Feasibility and Safety of Combining Anti-malarial With Deworming Drugs in African Children (MALHELMIN)

Feasibility and Effectiveness of Delivering Mass Drug Administration for Helminths Through the Seasonal Malaria Chemoprevention (SMC) Platform in a West African Paediatric Population

Malaria remains a major health problem, especially in sub-Saharan Africa where more than 90% of the disease and deaths occur in children. Adding to this high burden among the children is the co-existence of intestinal and genito-urinary worms. Prominent among these are soil-transmitted helminths and schistosomiasis. Existing control programmes for the worms are operating below the expected level, despite the commitments and support that followed the 2012 London Declaration of achieving 75% treatment coverage by 2020. On the other hand, a malaria prevention programme, called Seasonal Malaria Chemoprevention (SMC), introduced in the same year 2012 has achieved more than 75% treatment coverage and prevented 75-85% cases of uncomplicated and severe malaria in children. This encouraging development supports the need to explore the strategies involving the integration of worm control with successful platforms such as SMC. This would align worm and malaria control with the WHO road map for Neglected Tropical Diseases (NTD) of ending the neglect to attain Sustainable Development Goals by eradicating diseases of poverty and promoting health and well-being for those at risk. Given this context, it is important to develop a treatment approach that combines malaria and helminth control in an integrated framework that will be safe, effective and easy to deliver. This study will, therefore, investigate the feasibility and effectiveness of co-administration of anthelminthic and SMC drugs in a high-risk paediatric population living in a malaria-helminth co-endemic setting in Senegal, West Africa. This study is designed to test the hypothesis that co-administration of SMC and anthelminthic drugs will be safe and tolerated among children aged 1-14 years and that the incidence of side effects will not be significant. The objectives of this study are to assess the safety, tolerability, and effects of co-administration of SMC and anthelminthic drugs among the children

Study Overview

• Status: Active, not recruiting
• Conditions: Malaria; Schistosomiasis; Soil Transmitted Helminths; Integrated Control; Seasonal Malaria Chemoprevention; Mass Drug Administration With Anthelminthic Drugs
• Intervention / Treatment: Drug: Amodiaquine; Drug: Sulfadoxine pyrimethamine; Drug: Praziquantel; Drug: Albendazole

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Senegal
  • Kedougou
    • Saraya, Kedougou, Senegal, 00221
      • Saraya Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female children aged 1-14 years;
• Provision of a written informed consent by the parent/caregiver and a positive assent by children aged ≥ 12 years (in line with legal regulations in Senegal);
• Willingness to provide finger-prick blood samples, urine, and stool samples;
• Residence in the study area for at least six months

Exclusion Criteria:

• Acutely ill child at the time of the drug administration;
• Child whose parents/caregivers decline to provide consent;
• A known HIV positive child receiving cotrimoxazole prophylaxis;
• A child who has received a dose of any of sulphadoxine-pyrimethamine, amodiaquine, albendazole or praziquantel during the previous six months;
• A child with a known allergy to any of sulphadoxine-pyrimethamine, amodiaquine, albendazole or praziquantel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vitamin A + Zinc supplements on Day 0, followed by SMC course on Day 1,2 & 3	Drug: Amodiaquine; SMC partner drug; Drug: Sulfadoxine pyrimethamine; SMC partner drug
Experimental: Praziquantel + Vitamin A on Day 0, followed SMC course on Days 1,2 & 3	Drug: Amodiaquine; SMC partner drug; Drug: Sulfadoxine pyrimethamine; SMC partner drug; Drug: Praziquantel; Anthelminthic drugs for the treatment of schistosomiasis
Experimental: Albendazole + Praziquantel on Day 0, followed by SMC course on Days 1, 2 & 3	Drug: Amodiaquine; SMC partner drug; Drug: Sulfadoxine pyrimethamine; SMC partner drug; Drug: Praziquantel; Anthelminthic drugs for the treatment of schistosomiasis; Drug: Albendazole; Anthelminthic drugs for the treatment of soil-transmitted helminths

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Incidence of Treatment-Emergent Adverse Events will be measured by collecting solicited and unsolicited adverse events and adverse drug reactions for causal relationships to the study drugs.	For six consecutive days after start of the drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of helminth co-infection	Faecal egg counts for soil transmitted helminths	On the day of randomisation (pre-intervention) and up to 4 months post-intervention
Prevalence of Schistosoma co-infection	Urine egg counts for Schistosoma haematobium	On the day of randomisation (pre-intervention) and up to 4 months post-intervention
Prevalence of intensity of helminth infection	Arithmetic mean intensity of helminth infection	On the day of randomisation (pre-intervention) and up to 4 months post-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of anaemia	Haemoglobin concentration of all study children will be checked using HemoCue®	On the day of randomisation (pre-intervention) and up to 4 months post-intervention

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Université de Thies, UFR Santé, Senegal
• Investigators: Study Director: Brian Greenwood, MD, FMedSci, London School of Hygiene and Tropical Medicine

Publications and helpful links

General Publications

• Afolabi MO, Sow D, Ndiaye JLA, Greenwood B. Safety and effectiveness of delivering mass drug administration for helminths through the seasonal malaria chemoprevention platform among Senegalese children: study protocol for a randomised controlled trial. Trials. 2022 Aug 3;23(1):627. doi: 10.1186/s13063-022-06579-0.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2022
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Helminthiasis; Trematode Infections; Malaria; Schistosomiasis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Folic Acid Antagonists; Antiplatyhelmintic Agents; Anti-Infective Agents, Urinary; Renal Agents; Anticestodal Agents; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine; Albendazole; Praziquantel
• Other Study ID Numbers: 26770

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We will share the summary results of this trial or a link to the summary results within the trial registration record within 12 months of the study completion date
• IPD Sharing Time Frame: Within 12 months of the study completion date
• IPD Sharing Access Criteria: Open access requests will be entertained, the decision will be made by the Principal Investigator, quality of the request will be reviewed before granting it
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No