Treatment Study of Metronidazole to Treat Dientamoebiasis in Children (DFPT)

Metronidazole for the Treatment of Dientamoebiasis in Children in Denmark - A Randomized, Placebo-controlled, Double-blinded Clinical Trial

Introduction: Dientamoeba fragilis (DF) is a commonly occurring intestinal protozoan that is considered a possible cause of infectious gastrointestinal disease in adults and children. DF has a particular high prevalence in children, and it is suspected that children present more symptoms in infection than adults. However, evidence of causality is lacking, treatment regimens are largely untested in controlled trials, and the most commonly used antibiotic against DF in Denmark, metronidazole, has never been tested against placebo.

Main objective: To determine the clinical effect of metronidazole in DF-infected children with gastrointestinal complaints, where no other aetiology is known and no other gastrointestinal pathogens could be shown.

Study Overview

• Status: Completed
• Conditions: Dientamoebiasis
• Intervention / Treatment: Drug: Metronidazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2300
    • Statens Serum Institut

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with samples investigated at Statens Serum Institut.
• Faecal sample (index) positive for Dientamoeba fragilis (DF) by realtime PCR, within < 7 days.
• No faecal samples positive for DF within the period: 3 months prior to and up to index-sample.
• Telephone interview to parents no later then 14 days after result from index-sample.
• Age 3-12 years old.
• Place of residence: Island of Zealand, incl. capital region.
• Symptoms consistent with gastrointestinal infection of DF: Either 1) ≥ 2 episodes of diarrhea per week or 2) ≥ 2 episodes of stomach ache per week or 3) ≥ 2 of the following symptoms: Anorexia, Failure to thrive, Anal itching, excessive flatulence, other change in bowel movements.

Exclusion Criteria:

• Expected non-compliance.
• Objection to subject participation from referring physician.
• Underlying illness or comorbidity, incl. known gastrointestinal illness (both infectious and non-infectious), but excluding constipation.
• Known liver disease or intolerance/allergy to metronidazole.
• Positive screening for other intestinal pathogens, which may explain subject symptoms.
• Treatment with metronidazole outside of study within study period.
• Weight > 50 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metronidazole; Active treatment.	Drug: Metronidazole; Metronidazole, oral suspension, 40mg/ml. 1 treatment period of 40mg/kg/day for 10 days, 3 daily dosages. Administered by parents.; Other Names: Flagyl® (Metronidazole), oral suspension. Sanofi-aventis; ATC-code: P01AB01
Placebo Comparator: Placebo; Passive treatment.	Drug: Placebo; Placebo. 1 treatment period of 1ml/kg/day for 10 days, 3 daily dosages. Administered by parents. Placebo formulation is identical to Flagyl® (Metronidazole), oral suspension from Sanofi-Aventis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall gastrointestinal symptoms, day 14	All participants receive 10 days of treatment with study drug (placebo or active). Primary outcome measure is registered on day 14 after end of treatment, using a questionnaire for the parents of the study participant. Measuring will be done using a VAS-score scale, addressing overall level of gastrointestinal symptoms in the previous 14 days. Results will be noted as a value from 0 to 10.	14 days after end of treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Realtime PCR for D. fragilis, day 14	Secondary outcome measure will be registered using a specific realtime PCR for D. fragilis, performed on faecal samples collected from study-participant. Results will be noted as either positive or negative.	Sample collection 14 days after end of treatment period

Collaborators and Investigators

• Sponsor: Statens Serum Institut
• Investigators: Principal Investigator: Dennis Röser, MD, Statens Serum Institut; Study Director: Dennis Röser, MD, Statens Serum Institut

Publications and helpful links

General Publications

• Roser D, Simonsen J, Stensvold CR, Olsen KE, Bytzer P, Nielsen HV, Molbak K. Metronidazole therapy for treating dientamoebiasis in children is not associated with better clinical outcomes: a randomized, double-blinded and placebo-controlled clinical trial. Clin Infect Dis. 2014 Jun;58(12):1692-9. doi: 10.1093/cid/ciu188. Epub 2014 Mar 18.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: March 14, 2011
• First Posted (Estimate): March 15, 2011

Study Record Updates

• Last Update Posted (Estimate): June 26, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: treatment; Children; RCT; parasite; intestinal
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Diseases, Parasitic; Parasitic Diseases; Protozoan Infections; Dientamoebiasis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: DSR-01; 2010-024657-36 (EudraCT Number)