Evaluation of Praziquantel Dosage for Treatment of Schistosomiasis in Brazil
Condition: Schistosomiasis Mansoni
MeSH terms: Schistosomiasis; Schistosomiasis mansoni
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary objective of this project is to evaluate the efficacy and safety of praziquantel
      60 mg/kg in the treatment of schistosomiasis, as compared to the standard 40 mg/kg therapy in
      a representative community from a highly endemic area of schistosomiasis in Northeastern
      Brazil. Cure rates, reduction in egg counts and proportions of reported side-effects in
      children at the 10-19 y age-range with at least 100 eggs per gram of faeces will be compared
      between regimens, aiming to evaluate the superiority of 60 mg/kg over the 40mg/kg dose
      currently recommended by the WHO. Reinfection rates will also be evaluated aiming to improve
      transmission control within the local health system, including re-treatment combined with
      auxiliary control measures. Features related to the clinical, nutritional and immunological
      status of the patients prior to treatment will also be investigated in association with the
      outcome of praziquantel treatment.
    

Detailed description: 
      This is a double blind, randomized, PZQ 40mg/Kg- controlled clinical trial. Subjects 10-19
      years old living in communities of the Northeast of Brazil will be identified and invited to
      participate in this study.

      Well trained field health agents will first make a sketch map of the village (depicting the
      location of houses, main water courses, snail habitats and water-contact sites) and apply a
      household questionnaire to obtain personal data from residents to identify the individuals in
      the 10-19 years age range, as well as to record sanitary standards of the houses and
      water-contact reported behaviour as described by Pieri et al. (1998, Mem. Inst. Oswaldo Cruz,
      93, Suppl 1: 259-264).

      Meetings with the Caricé Community Association will be held in order to explain to the
      inhabitants the purpose, the objectives of the study, and how the study will be conducted.

      Thereafter, all residents between 10 and 19 yrs of age will be interviewed at their homes
      regarding the fulfilment of the inclusion/exclusion criteria. Those who fulfil the criteria
      and agree to participate in the screening phase of the trial (signed Screening Informed
      Consent) will be given stool vials and asked to provide stool samples (two samples within
      5-day intervals) that will be collected at their homes in the following days, stored in
      heat-proof containers and taken to the premises of the Service of Reference for
      Schistosomiasis Diagnosis of the CPqAM to be promptly prepared for examination by the
      Kato-Katz method (Katz et al, 1972, Rev. Inst. Med. Trop. Sao Paulo, 14: 397-400) aiming to
      identify positive cases and estimate individual egg load. Females on childbearing age will
      also be asked to provide a urine sample for pregnancy test. Pregnant women will only be
      treated with Praziquantel after weaning, as currently recommended by Funasa, and will be
      excluded from the trial. The 2 stool samples provided by each individual will be analysed for
      S. mansoni infection. Two slides will be prepared from each stool sample, and the mean value
      of the 4 slides (as measured by number of eggs/g of stool) will be calculated. Only those
      harbouring at least 100 epg who are able and willing to follow-up will be invited to
      participate in the study. At this stage, individuals with positive diagnosis for S. mansoni
      and that for any reason were excluded from the study will receive standard treatment for
      schistosomiasis.

      In the enrolment visit the subjects eligible for the study, will be examined by the physician
      and interviewed to assess inclusion/exclusion criteria. Those who fulfill all criteria will
      be invited to participate in the trial and will go through the Informed Consent Form
      procedure (see details in section 6.14). For those who accept to participate and provide a
      written Informed Consent: weight and height will be measured, a 5ml venous blood sample will
      be collected and an abdominal ultra-sound exam will be performed. After all these procedures,
      the patient will be assigned to the treatment.

      Subjects will be randomly allocated to either Group A (single 40 mg/kg oral dose) or Group B
      (single 60 mg/kg oral dose), as described in sections 6.4.3 and 6.4.4. Praziquantel tablets
      will be provided by TDR. During four hours after treatment the subjects will be observed for
      safety assessment, and one day and 21 days after treatment they will be interviewed about the
      following symptoms related to praziquantel side-effects: abdominal pain, diarrhea, vomiting,
      nausea, drowsiness, general malaise, edema, skin rash, urticaria, myalgia, heartburn, fever,
      dizziness and headache (Guisse et al, 1997, Am. J. Trop. Med. Hyg., 56: 511-514, 1997). The
      follow-up visits to assess efficacy and morbidity will be at 21 days, six months and 12
      months after treatment, when the subjects will be surveyed by the Kato-Katz method (two stool
      samples within five-day interval, two slides each). Weight and height will be measured at 6
      and 12 months follow-up. Ultrasound will be repeated at 6 and 12 months follow-up visits for
      the participants who presented periportal fibrosis or liver/spleen enlargement in the
      baseline (D0) exam.
    

Intervention name(s): Praziquantel 60 mg/kg; Praziquantel 40 mg/kg
Intervention type(s): Drug; Drug
Intervention description(s): Praziquantel (Distocide) 60 mg/kg single oral dose; Praziquantel (Distocide) 40 mg/kg single oral dose
Other intervention name(s): Distocide; Distocide
Intervention MeSH terms: Praziquantel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment