Safety and Efficacy of Single Daily Dose of Ceftriaxone and Metronidazole for Treatment of Complicated Appendicitis in Children

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dan Miron, MD, HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier:
NCT01678365
First received: July 24, 2012
Last updated: September 3, 2012
Last verified: September 2012
  Purpose

A prospective open randomized study conducted between July 1st 2008 and June 30th, 2009. Included were children younger than 14 years with Complicated appendicitis randomly assigned either to a single daily dose of Ceftriaxone and Metronidazole or Ampicillin, Gentamicin, and Metronidazole. The outcome variables compared were: maximum daily temperatures, overall duration of fever, time return to oral intake, length of antibiotic therapy, results of repeat WBC measure, general/intra abdominal complications, need for intra abdominal abscess drainage, Length of stay and adverse reaction.


Condition Intervention Phase
Complicated Appendicitis
Drug: ceftriaxone, metronidazole/ampicillin, gentamicin, and metronidazole
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Single Daily Dose of Ceftriaxone and Metronidazole for Treatment of Complicated Appendicitis in Children

Resource links provided by NLM:


Further study details as provided by HaEmek Medical Center, Israel:

Primary Outcome Measures:
  • Length of stay (days) [ Time Frame: From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks ] [ Designated as safety issue: No ]
  • Change of primary antibiotic regimen to Piperacillin/tazobactam [ Time Frame: From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of new intrabdominal abcesses [ Time Frame: From admission to discharge from of first admission (if there are more than one), an expected average 2 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Re hospitalization due to intra abdominal abcess formation [ Time Frame: Within 2 years after day of discharge ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: July 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ceftriaxone and metronidazole for complicated appendicitis.
Children with complicated appendicitis treated with single daily dose of ceftriaxone and metronidazole.
Drug: ceftriaxone, metronidazole/ampicillin, gentamicin, and metronidazole
Active Comparator: Ampicillin, gentamicin, and metronidazole
Children with complicated appendicitis treated with ampicillin, gentamicin, and metronidazole
Drug: ceftriaxone, metronidazole/ampicillin, gentamicin, and metronidazole

Detailed Description:

The study was conducted at the Pediatric Surgery Department at HaEmek Medical Center, Afula, Israel. Included were children age 1-14 years with complicated appendicitis that was defined by one of the followings: 1. Demonstration by abdominal ultrasound and/or computed tomography of appendix perforation and/or peri-appendicular abscess 2. Demonstration by abdominal ultrasound of free fluid, and signs of diffuse peritoneal irritation in the right lower quadrant of the abdomen 3. At surgery performed for suspected non complicated appendicitis. In a patient with perforate appendicitis that was diagnosed at surgery, appendectomy was performed by one of the 4 senior pediatric surgeons on call at the time of the child's admission. Exclusion criteria were: documented allergy to any of the study medications, acute or renal insufficiency at admission, and severe septic shock at admission.

Therapeutic approach: After the diagnosis of complicated appendicitis was established, patients were randomly assigned to therapy with either once daily of ceftriaxone and metronidazole or ampicillin, gentamicin and metronidazole. Therapy was change to piperacillin/tazobactam in patients who were still febrile at day 7-10 of the admission (if not given before), based on the clinical situation, and in all febrile patients at 11 day of the admission . All patients had also been treats after inclusion with pain control medications, no oral food or fluid , and intravenous hydration as necessary. Nasogastric tubes were not used routinely. On the fifth admission day patients who were stable, a febrile, could tolerate diet and had Complete blood count within normal limits were discharged home with oral amoxicillin/clavulanate therapy for further 7 days.

Follow-up at the admission: CBC and renal and liver function tests were obtained before starting the antibiotic treatment and repeated on day 4 in all patients. In the group treated with AGM, serum trough gentamicin concentration was drawn before the fourth dose with normal level considered as < 2 mcg/ml. Other blood studies were performed based on the discretion of the attending physician based on the patient's clinical status. For patients who were either febrile or had leukocytosis, at day 5 of therapy abdominal ultrasound was obtained to assess for the presence of an abscess. Patients in whom abscesses were delectated undergone per coetaneous drainage (when possible). The original antibiotic regimen was either continued or changed to piperacillin/tazobactam based on the clinical situation. Patients, in whom appendectomy had not been done at admission, were readmitted for appendectomy at 6 weeks. All patients had been followed for a year since the admission for signs of intra abdominal complication such: repeat abscess formation, repeat admission, obstruction etc.

Data collection: Data were recorded were: patient's age, weight, gender, maximum daily temperature, duration of fever, results of complete blood count, renal and liver function tests, gentamicin levels (where applicable), intra abdominal complications and duration of hospitalization. The outcome variables included maximum daily temperatures for each of the first 10 postoperative days, time to initial oral intake, length of hospitalization, length of antibiotic therapy, abscess formation rate, need to change antibiotic regimen, wound infection rate, and any abnormal findings during the follow-up visits.

Statistical analysis: Since data in the literature show that there is no difference of the length of stay in between the 2 regimens (in children with complicated appendicitis following operation), and most studies included relatively low number of patients, no power analysis was calculated. The difference between various parameters in the two treatment groups were assessed by 2 independent sample T tests or Fisher exact tests for categorical data and 2 independent sample t test or the Mann Whitney test for continuous data. Descriptive statistics were calculated as mean ± SD.

  Eligibility

Ages Eligible for Study:   1 Year to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children age 1-14 years CA that was defined by one of the followings:

    1. Demonstration by abdominal ultrasound (US) and/or computed tomography (CT) of appendix perforation and/or peri-appendicular abscess
    2. Demonstration by abdominal ultrasound (US) of free fluid, and signs of diffuse peritoneal irritation in the right lower quadrant of the abdomen 3

Exclusion Criteria:

  • Documented allergy to any of the study medications, acute or renal insufficiency at admission, and severe septic shock at admission.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678365

Locations
Israel
Pediatric Surgery Department, HaEmek Medical Center
Afula, Israel, 18101
Sponsors and Collaborators
HaEmek Medical Center, Israel
  More Information

No publications provided

Responsible Party: Dan Miron, MD, Professor, HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier: NCT01678365     History of Changes
Other Study ID Numbers: 043-07-EMC
Study First Received: July 24, 2012
Last Updated: September 3, 2012
Health Authority: Israel: Ministry of Health

Keywords provided by HaEmek Medical Center, Israel:
complicated appendicitis
Children
conservative therapy
Study population: Children 1 month - 14 years with Complicated appendicitis
Type of the study: prospective, open randomized

Additional relevant MeSH terms:
Appendicitis
Acute Disease
Intraabdominal Infections
Infection
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Cecal Diseases
Intestinal Diseases
Disease Attributes
Pathologic Processes
Ampicillin
Ceftriaxone
Gentamicins
Metronidazole
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiprotozoal Agents
Antiparasitic Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 01, 2014