Once Daily Metronidazole for Perforated Appendicitis

Appendicitis Clinical Trial

— METRO  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02561117
• Other study ID #: 4660
• Status: Withdrawn
• Phase: Phase 4
• First received: September 23, 2015
• Last updated: July 18, 2017
• Start date: January 2019
• Est. completion date: January 2022

Study information

• Verified date: July 2017
• Source: Children's Hospital of Eastern Ontario
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2022
• Est. primary completion date: January 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Appendicitis

Intervention

Drug:
• Metronidazole
Administration once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ahmed Nasr

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of stay	• 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	Failure of antibiotics	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)
Secondary	Quantity of narcotics	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.
Secondary	Duration of narcotics	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.
Secondary	Duration of antibiotics IV	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.
Secondary	Duration of antibiotics oral	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.
Secondary	Theoretical cost in CAD	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.