{
  "abstract": "Objective This study assessed the feasibility of implementing a phase 3 field-based clinical trial protocol to evaluate paediatric praziquantel (PED-PZQ) for the treatment of Schistosoma mansoni infection in children aged 3 months to 6 years in endemic areas of Brazil, focusing on operational aspects such as recruitment logistics, documentation management, investigational product handling and protocol adherence.Design Pilot and feasibility study for a phase 3 clinical trial, comprising two components: a randomised, open-label, parallel-group, two-arm trial and a single-arm trial.Setting Conde, Bahia, Brazil, from December 2024 to January 2025.Participants Two trials aim to screen 5774 participants from three rural areas in Bahia and three in Sergipe, states in northeastern Brazil, and enrol 403 children eligible for either randomisation or allocation. Trial 1 will randomise (1:1 ratio) 240 children aged 4–6 years into the PED-PZQ treatment arm or the standard praziquantel (PZQ) 1. Trial 2 will enrol 163 children aged 3 months to 3 years, all receiving PED-PZQ. Both trials are open label. Eligible participants shall meet age criteria, test positive for S. mansoni and fulfil other inclusion criteria. In the first recruiting centre, Conde (Bahia), it was estimated that 650 participants would need to be screened for trial 1 and 552 for trial 2, assuming schistosomiasis prevalence of 5% and 4%, respectively. This pilot study reports on the first 60 participants enrolled.Primary and secondary outcome measures The primary outcome of this pilot study is the feasibility of implementing the research protocol in a real-world field setting, focusing on key aspects such as study documentation challenges, participant safety, investigational medicinal product custody chain and protocol adherence. In addition to providing preliminary data on the parasitological cure rate, secondary outcomes include the prevalence of S. mansoni infection and the reduction in S. mansoni egg count (Kato-Katz method). Furthermore, the occurrence and severity of drug-related adverse events are monitored from drug administration to day 21 post-treatment, alongside changes in renal, hepatic and cardiac functions assessed through biochemical markers.Results A total of 60 participants were recruited, and 55 provided stool samples for screening. The pilot phase demonstrated the feasibility of implementing the clinical protocol under field conditions, with successful completion of all planned procedures and minimal protocol deviations. Operational challenges were identified mainly in documentation processes, participant recruitment and investigational product management and were addressed through preventive and corrective quality assurance actions. The experience also highlighted logistical and infrastructural barriers typical of field-based trials in remote endemic areas, which informed adjustments for the subsequent phase 3 study. Preliminary parasitological results indicated an overall S. mansoni prevalence of 9.1% (5/55), with 21% in trial 1 and 2.8% in trial 2. All infected participants met the eligibility criteria, received treatment and completed follow-up. Four achieved a parasitological cure, and one case of treatment failure was observed (trial 1, PZQ group). Two mild adverse events (diarrhoea) were reported, with no serious complications or clinically significant changes in biochemical parameters.Conclusions This pilot study demonstrated the feasibility of implementing a field-based phase 3 clinical trial protocol for PED-PZQ in endemic areas of Brazil. The findings confirm that the protocol can be successfully applied in primary care settings, despite operational challenges related to recruitment, logistics and documentation. The study also provided preliminary evidence supporting the safety and effectiveness of the paediatric formulation and highlighted the need to revise prevalence assumptions to improve future screening strategies. Overall, the experience offers valuable insights to guide the large-scale phase 3 trial and supports the incorporation of PED-PZQ into national schistosomiasis control policies.Trial registration number Brazilian Clinical Trials Registry; RBR-86kcy37.",
  "authors": [
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Camilla Almeida Menezes"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Ane Caroline Casaes"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Brenda Rodrigues Brito Cunha Silva"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Maria Gabriella Brito dos Santos"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Caio Daroz Martins"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Ivia Mayana Oliveira Francisco"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Keila Ramos dos Santos"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Bruna Oliveira Lopes Souza"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Alan Gualberto Souza Freitas Pinho"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Dhara Marina Oliveira Brito Mayer"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Gisella Pinto da Rocha Martinelli Moleiro"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Lorena Conceição de Queiroz"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Ramila Marques Nascimento"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Roseanne Oliveira Silva"
    },
    {
      "affiliations": [
        "Universidade Federal da Bahia, Salvador, Brazil"
      ],
      "name": "Robson da Paixão de Souza"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Luciano Kalabric Silva"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Mitermayer Galvão Reis"
    },
    {
      "affiliations": [
        "Universidade Federal do Espírito Santo Centro de Ciências da Saúde, Vitoria, Brazil"
      ],
      "name": "Carlos Graeff-Teixeira"
    },
    {
      "affiliations": [
        "Universidade Federal de Sergipe, São Cristóvão, SE, Brazil"
      ],
      "name": "Silvio Santana Dolabella"
    },
    {
      "affiliations": [
        "Vice-Presidência de Pesquisa e Coleções Biológicas (VPPCB), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil"
      ],
      "name": "Livia Cristina Carneiro"
    },
    {
      "affiliations": [
        "Vice-Presidência de Pesquisa e Coleções Biológicas (VPPCB), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil"
      ],
      "name": "Tatiana Camilo Ribeiro de Senna"
    },
    {
      "affiliations": [
        "Vice-Presidência de Pesquisa e Coleções Biológicas (VPPCB), Fundação Oswaldo Cruz, Rio de Janeiro, Brazil"
      ],
      "name": "Andre Daher"
    },
    {
      "affiliations": [
        "Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil"
      ],
      "name": "Daniel Lacerda de Oliveira"
    },
    {
      "affiliations": [
        "Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil"
      ],
      "name": "Juliana Johansson Soares Medeiros"
    },
    {
      "affiliations": [
        "Universidade Federal do Ceará, Fortaleza, Brazil"
      ],
      "name": "Fernando Schemelzer de Moraes Bezerra"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Isadora Cristina de Siqueira"
    },
    {
      "affiliations": [
        "FIOCRUZ Bahia, Salvador, Brazil"
      ],
      "name": "Ricardo Riccio Oliveira"
    }
  ],
  "title": "Feasibility of a phase 3 partially randomised clinical trial to assess the safety and efficacy of paediatric praziquantel for schistosomiasis treatment in children aged 3 months to 6 years in endemic regions of Brazil: a pilot study",
  "uid": "f7a1bb04-7b6b-5a47-b47d-55091cfb97d6"
}