Evaluation of Praziquantel Dosage for Treatment of Schistosomiasis in Brazil
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.
Drug: Praziquantel 60 mg/kg
Drug: Praziquantel 40 mg/kg
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Evaluation of Praziquantel Dosage for Treatment of Schistosomiasis in Highly Endemic Areas of Northeastern Brazil|
- Cure rate and egg reduction rate at twenty-one days after treatment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Occurrence of the following symptoms following praziquantel administration: abdominal pain, diarrhea, vomiting, nausea, drowsiness, general malaise, edema, skin rash, urticaria, myalgia, heartburn, fever, dizziness and headache. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
- Weight (Kg) and height (m) measured at Day 0, 6 months and 12 months follow-up visits. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Presence/absence of periportal fibrosis and liver or spleen enlargement at Day 0, 6 months and 12 months follow-up visits. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Factors associated with cure/failure at Day 21 evaluation: [ Time Frame: 21 days ] [ Designated as safety issue: No ]
- Haematological: Haemoglobin/ Hematocrit, leukocytes count, lymphocytes and eosinophiles count. [ Time Frame: 0 days ] [ Designated as safety issue: No ]
- Biochemistry: liver function will be evaluated by serum bilirubin, alkaline phosphatase, aspartate aminotransferase, and alamin aminotransferase levels. [ Time Frame: 0 days ] [ Designated as safety issue: No ]
- Immunological: Titles of anti-SEA and anti-SWAB antibodies. [ Time Frame: 0 days ] [ Designated as safety issue: No ]
- Reinfection rate and Egg reduction rate at six and twelve months after treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2006|
|Study Completion Date:||May 2008|
|Primary Completion Date:||October 2007 (Final data collection date for primary outcome measure)|
Active Comparator: Praziquantel 40mg/kg
Praziquantel (Distocide) 40mg/kg single oral dose
Drug: Praziquantel 40 mg/kg
Praziquantel (Distocide) 40 mg/kg single oral dose
Other Name: Distocide
Experimental: Praziquantel 60mg/kg
Praziquantel (Distocide) 60mg/kg single oral dose
Drug: Praziquantel 60 mg/kg
Praziquantel (Distocide) 60 mg/kg single oral dose
Other Name: Distocide
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00403611
|Principal Investigator:||Otavio S Pieri, PhD||Fundação Oswaldo Cruz|
|Principal Investigator:||Ana Lucia C Domingues, MD||Universidade Federal de Pernambuco|