Oral Nitazoxanide in Acute Gastroenteritis in Australian Indigenous Children

NCT02165813 | Terminated Phase 2 DMC

• 1 other identifier: NICEGUT
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-centre (RDH and ASH), phase IV, double-blind, randomised, placebo-controlled Bayesian adaptive trial of oral NTZ for the treatment of acute gastroenteritis requiring admission to hospital. A maximum of 300 children aged between three months and less than five years of age will be enrolled. Study participation is from the point of enrolment until 60 days after enrolment. Enrolment will occur within 48 hours of admission to hospital. Enrolled participants will be randomised 1:1 to Nitazoxanide (NTZ) or placebo. Other treatment and management will be as per the standard of care described in the admitting hospital's guidelines and will be ultimately the decision and responsibility of the named medical consultant. Stool samples will be collected at the point of admission. Solicitation of symptoms will be by review of routinely collected medical data recorded in the participant's medical record, and will be supplemented by completion of study specific diary cards after discharge (for the first 210 enrolments). Attempts will be made to contact participants at day 7 after enrolment (by telephone if already discharged) to ascertain symptoms occurring in the intervening period. At days 30 and 60 (for first 210 enrolments ) and Day 60 (for enrolment #211 onwards) after enrolment a clinical record review will be conducted for all participants to ascertain health care attendances following discharge.

Conditions

Gastroenteritis

Outcome Measures

Primary Outcomes (1)

• Time of significant illness

  The time period of significant illness (defined as the period for which hospitalisation is required for medical reasons) for participants in each study treatment group.

  Between randomisation and hospital discharge (expected to be within 7 days)

Secondary Outcomes (1)

• Time to hospital discharge

  Between randomisation and hospital discharge (expected to be within 7 days)

Other Outcomes (4)

• Symptom frequency (vomiting, diarrhoea, generally unwell)

  On each of study days 0-7

• Dehydration frequency and severity

  On each of study days 0-7

• Time of intravenous, intraosseous or nasogastric rehydration

  7 days post randomisation

Study Arms (2)

Nitazoxanide

ACTIVE COMPARATOR

oral nitazoxanide suspension twice daily for 3 days

Drug: Nitazoxanide

Placebo

PLACEBO COMPARATOR

oral placebo suspension twice daily for 3 days

Drug: placebo

Interventions

Nitazoxanide DRUG

Nitazoxanide is a synthetic drug of the nitrothiazolide class. The main metabolite of NTZ is tizoxanide. The active ingredient is Nitazoxanide (2-acetyloxy-N(5-nitro-2-thiazolyl)benzamide), a synthetic agent for oral administration, at a concentration of 100 mg/5 ml.

Also known as: Alinia

Nitazoxanide

placebo DRUG

An oral suspension is supplied as a pink coloured powder formulation (sugar) that is reconstituted with 48 mL water prior to use to a final volume of 60 mls.

Placebo

Eligibility Criteria

• Age: 3 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infant /child between =\>3 months and \<5 years of age
• Infant/ child identified as Indigenous by the legally responsible care-giver
• Infant /child has been/will be admitted to hospital for acute infectious gastroenteritis (in the opinion of the admitted doctor and/or study doctor/nurse )
• The legally responsible care-giver is willing for their infant/ child to participate in the study and who would be expected to comply with the requirements of the protocol, including being able and willing to be contacted by telephone after discharge where necessary
• The legally responsible care-giver is willing to allow other parties involved in the treatment of his or her child (including the general practitioner, paediatrician, hospital medical and nursing staff, community clinic staff) to be notified of participation in the trial
• The legally responsible care-giver is willing to allow to allow the study team to obtain a vaccination history from Australian Childhood Immunisation Register (ACIR) and/or local provider
• The legally responsible care-giver is willing to allow the study team to obtain an interim medical history from the participant's electronic medical records and/or from the participant's general practitioner for the period from enrolment to study day 60
• Informed consent for the infant's/child's participation in the study has been given by the legally responsible care-giver

You may not qualify if:

• Admitted for =\>48 hours at the point of enrolment
• Duration of symptoms of greater than 14 days without apparent worsening of symptoms consistent with an acute pathology
• Presence of grossly bloody diarrhoea
• Clinical suspicion of non-infectious cause (e.g. diagnosed with a pre-existing medical condition predisposing to non-infectious diarrhoea, for example inflammatory bowel disease) except for environmental enteropathy)
• Contraindication to the study drug or placebo (e.g. allergy)
• Diagnosis of infection with an enteric pathogen where anti-microbial treatment with an alternative antimicrobial is the standard of care (e.g. Shigella sp.)
• Inability to tolerate either the oral or nasogastric route (e.g. ileus)
• Clinical suspicion of intestinal obstruction including bilious vomiting
• Confirmed or suspected immunosuppressive or immunodeficient conditions, including human immunodeficiency virus (HIV) infection.
• Receipt of more than 2 weeks of immuno-suppressants or immune modifying drugs, (e.g. prednisolone \>0.5 mg/kg/day)
• Receipt of investigational drug/vaccine, other than the drugs used in the study, within 30 days prior to receiving the first dose of NTZ or their planned use during the study period, until 1 month after the administration of the final dose of NTZ
• Previously enrolled in the trial

Sponsors & Collaborators

• Telethon Kids Institute: lead
• The University of Western Australia: collaborator
• Menzies School of Health Research: collaborator

Study Sites (2)

Alice Springs Hospital

Alice Springs, Northern Territory, 0872, Australia

Location

Royal Darwin Hospital

Darwin, Northern Territory, 0800, Australia

Location

Related Publications (1)

• Waddington CS, McLeod C, Morris P, Bowen A, Naunton M, Carapetis J, Grimwood K, Robins-Browne R, Kirkwood CD, Baird R, Green D, Andrews R, Fearon D, Francis J, Marsh JA, Snelling T. The NICE-GUT trial protocol: a randomised, placebo controlled trial of oral nitazoxanide for the empiric treatment of acute gastroenteritis among Australian Aboriginal children. BMJ Open. 2018 Feb 1;8(2):e019632. doi: 10.1136/bmjopen-2017-019632.

  PMID: 29391385 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Gastroenteritis

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Tom Snelling

  Sydney University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Matched placebo formulation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Bayesian piecewise survival analysis

Study Record Dates

• First Submitted: June 9, 2014
• First Posted: June 18, 2014
• Study Start: November 1, 2014
• Primary Completion: April 21, 2021
• Study Completion: June 6, 2021
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

AU (2)