Once Daily Metronidazole for Perforated Appendicitis (METRO)

July 18, 2017 updated by: Ahmed Nasr

Metronidazole Every 24 Hours as Part of Triple Antibiotic Therapy for Ruptured Appendicitis in Children Managed Operatively (METRO): a Noninferiority Randomized Controlled Trial

The objective of this study is to determine whether administering once-daily doses of metronidazole, an intravenous (IV) antibiotic used to prevent infection in perforated appendicitis, is as effective in children as delivering it in the standard method of once every eight hours. Reducing the frequency of administration has the potential of decreasing personnel time and healthcare cost and increasing the lifespan of the IV line.

To determine the effectiveness once-daily administration, a randomized controlled trial (RCT) will be conducted to compare outcomes between the two treatment schedules. We will recruit 100 patients (50 per treatment) aged 5-18 being surgically treated for perforated appendicitis at the Children's Hospital of Eastern Ontario, who will be randomly assigned to one of the two treatment schedules. To compare the efficacy of the treatments, outcomes such as duration of hospital stay and theoretical cost will be measured and analyzed using statistical tests.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All children 5-18 years of age, presenting to CHEO with perforated appendicitis (confirmed either in the operating room or diagnosed preoperatively according to radiological criteria), and managed surgically will be assessed for eligibility to participate. These patients may participate if baseline lab values of serum AST (SGOT), AL T (SGPT), LDH, triglycerides and hexokinase glucose are normal, complete physical exam is normal, hGC test is negative for pregnancy (if the patient is a female of reproductive age) and none of the exclusion criteria are present.

Exclusion Criteria:

  • Any known co-existing gastrointestinal disease
  • Uncertainty about the diagnosis
  • Perforated appendicitis with diffuse abdominal fluid on imaging associated with a clinical picture of severe sepsis
  • A known allergy to any of the antibiotics to be used in this trial
  • An active neurological disorder
  • Receiving medical treatment for a neurological disorder
  • A history of blood dyscrasia, hypothyroidism or hypoadrenalism
  • Hepatic disease
  • Renal impairment
  • Patients receiving any other oral or intravenous concomitant antimicrobial at enrollment
  • Pregnancy
  • Under five years of age
  • Patients who have received metronidazole orally or intravenously in the last 14 days, prior to the current admission for appendicitis
  • Patients already taking any of the following medications at admission (as these may interact with Metronidazole as stated in the product monograph): disulfiram, oral anticoagulant therapy (warfarin type), phenytoin or phenobarbital, vecuronium, lithium, busulfan
  • The physician elects to treat the patient conservatively (non-surgically)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: q8h
Metronidazole given every 8 hours
Drug: Metronidazole
Administration once daily
Other Names:
  • Flagyl
Experimental: q24h
Metronidazole given once daily
Drug: Metronidazole
Administration once daily
Other Names:
  • Flagyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of stay
Time Frame: until discharge (usually less than one week after admission)
• Duration of hospital stay (in days) during initial admission for perforated appendicitis (Patient will be discharged when eating normal diet, afebrile for 24 hours and no abdominal pain)
until discharge (usually less than one week after admission)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Failure of antibiotics
Time Frame: during hospital stay (usually less than one week)
o No clinical improvement after five days, as decided by the patient's surgeon. This will result in the patient being switched to a regimen of different antibiotics.
during hospital stay (usually less than one week)
Quantity of narcotics
Time Frame: From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
mg/kg per day of narcotics
From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
Duration of narcotics
Time Frame: From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
total number of days of narcotics
From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
Duration of antibiotics IV
Time Frame: From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
duration of IV antibiotic therapy (days)
From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
Duration of antibiotics oral
Time Frame: From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
duration of oral antibiotic therapy following discharge (days)
From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
Theoretical cost in CAD
Time Frame: From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.
In our study, due to blinding, much of the potential cost-savings of once-daily administration of metronidazole - including nursing time, pharmacy time, and IV materials - will not be evident. However, we will calculate the potential cost-savings of once-daily administration. This will be based on number of hours of nursing time saved (the research coordinator (RC) will, on 10 occasions, observe a nurse administering a dose of metronidazole to a patient not enrolled in this study, and will average these to estimate the time required to administer one dose), number of hours of pharmacy time saved (the RC will, on 10 occasions, observe a pharmacist preparing a dose of metronidazole for a patient not enrolled in this study, and will average these to estimate the time required to prepare one dose), and cost saved on materials (the minibag used to deliver the antibiotic, the IV needle and line if it needed to be replaced, etc.)
From date of randomization to date of death from any cause or three months after initial discharge from hospital, whichever comes first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ahmed Nasr

Investigators

  • Principal Investigator: Ahmed Nasr, CHEO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2019

Primary Completion (Anticipated)

January 1, 2021

Study Completion (Anticipated)

January 1, 2022

Study Registration Dates

First Submitted

September 23, 2015

First Submitted That Met QC Criteria

September 24, 2015

First Posted (Estimate)

September 25, 2015

Study Record Updates

Last Update Posted (Actual)

July 21, 2017

Last Update Submitted That Met QC Criteria

July 18, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4660

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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