Antibiotic Instillation in Appendicitis

NCT ID: NCT05470517

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-05
• Study Completion Date: 2024-03-20

Brief Summary

Appendicitis (inflammation of the wall of the appendix, causing pain and tenderness in the abdomen) has a range of severity that goes from simple to complicated. Complicated appendicitis may present with infected fluid inside of the abdomen or a perforation or hole in the intestines.

This research is being done to determine if placing an antibiotic solution in the abdomen at the time the appendix is removed is a safe procedure in patients between the ages of 3 and 18 years old with findings of complicated appendicitis.

Johns Hopkins All Children's Hospital (JHACH)'s current standard of care for patients with complicated appendicitis includes suctioning the infected fluid out of the abdomen at the time the appendix is removed. As part of this study, the investigators would like to see if patients with complicated appendicitis will benefit from routine care plus leaving an antibiotic solution inside the abdomen, after fully suctioning the infected fluid out of the abdomen.

Detailed Description

Appendicitis is one of the most common surgical diagnoses in the pediatric population and the most common surgical emergency in children. In complex appendicitis, the sequelae have progressed beyond the confines of the organ, and have led to purulent fluid in the intra-abdominal space, spillage of intestinal contents, or gross perforation of the appendix. Complicated appendicitis occurs in up to 20% of cases and is associated with a much higher morbidity and mortality. Previous studies have shown that local treatment of peritonitis associated with peritoneal dialysis (PD) catheters with intra-peritoneal antibiotics has had significant improvement of outcomes. The intra-peritoneal route is preferable as compared to oral and intravenous antibiotic administration due to elevated local levels of the antibiotic above the minimum inhibitory concentration while avoiding venipuncture and systemic side effects. There is minimal risk associated with involvement in this study given that the investigators will be screening for any history of allergies to penicillin or cephalosporins, and excluding these patients. Ceftriaxone is commercially available, has a low risk profile, and is generally well tolerated with minimal side effects.

The investigators' treatment period will include a one-time intra-operative dose of intra-peritoneal ceftriaxone (or an appropriate second or third generation cephalosporin to be designated at the discretion of the institutional Antibiotic Stewardship committee should ceftriaxone be unavailable). Typical dosing strategies for intra-peritoneal ceftriaxone administration occur on a daily basis, so the investigators' treatment period will also include the 24 hours following intra-peritoneal administration of ceftriaxone. All patients diagnosed with acute complicated appendicitis intra-operatively, and entered into the investigators' study, will also receive a minimum 48 hours of intravenous antibiotics as an inpatient, allowing for continued observation. The investigators will be treating pediatric patients who are intra-operatively diagnosed with complex appendicitis, as defined by any of the following: visible hole in the appendix, extra-luminal fecalith, diffuse fibropurulent exudate outside the right lower quadrant (RLQ)/pelvis, or intraperitoneal abscess. All patients will have been admitted to Johns Hopkins All Children's Hospital with a diagnosis of acute appendicitis prior to surgical intervention. Patients will then be randomized once diagnosed with complex appendicitis intra-operatively. Patients with allergies to penicillin or cephalosporins will be excluded pre-operatively, as well as patients who do not meet the weight requirement, are pregnant, being treated non-operatively, and those who have been intra-operatively diagnosed with simple appendicitis.

Conditions

Complicated Appendicitis; Acute Appendicitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard of Care (Arm A)

Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy.

Group Type: ACTIVE_COMPARATOR

Intra-peritoneal Fluid Aspiration

Intervention Type: PROCEDURE

Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy.

Standard of Care and Antibiotic instillation (Arm B)

Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy and subsequent instillation of 10ml of intra-peritoneal ceftriaxone (2g)

Group Type: EXPERIMENTAL

Ceftriaxone

Intervention Type: DRUG

Ceftriaxone is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous, intramuscular, or intra-peritoneal administration.

Ceftriaxone is a white powder, which is soluble in water. In this study ceftriaxone crystalline powder will be dissolved in 0.9% sodium chloride solution prior to intra-peritoneal instillation.

Antibiotic instillation will be introduced into the RLQ/pelvis after the appendectomy is completed and all intra-peritoneal fluid is aspirated. Ceftriaxone solution will be used depending on availability and pharmacy stock for use at Johns Hopkins All Children's Hospital. The ceftriaxone powder (2g) will be dissolved in 9ml of sterile normal saline, for a total instillation volume of 10ml. This fluid will then be instilled and left to dwell in the area of the peritoneal cavity where the appendix was removed.

Intra-peritoneal Fluid Aspiration

Intervention Type: PROCEDURE

Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy.

Interventions

Ceftriaxone

Ceftriaxone is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous, intramuscular, or intra-peritoneal administration.

Ceftriaxone is a white powder, which is soluble in water. In this study ceftriaxone crystalline powder will be dissolved in 0.9% sodium chloride solution prior to intra-peritoneal instillation.

Antibiotic instillation will be introduced into the RLQ/pelvis after the appendectomy is completed and all intra-peritoneal fluid is aspirated. Ceftriaxone solution will be used depending on availability and pharmacy stock for use at Johns Hopkins All Children's Hospital. The ceftriaxone powder (2g) will be dissolved in 9ml of sterile normal saline, for a total instillation volume of 10ml. This fluid will then be instilled and left to dwell in the area of the peritoneal cavity where the appendix was removed.

Intervention Type: DRUG

Intra-peritoneal Fluid Aspiration

Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy.

Intervention Type: PROCEDURE

Other Intervention Names

Ceftriaxone sodium

Eligibility Criteria

Inclusion Criteria

• Diagnosed with acute appendicitis and are scheduled to undergo urgent appendectomy
• Between 3-18 years of age at time of appendectomy
• Has intraoperative findings of complex appendicitis defined by: visible hole in the appendix, extra-luminal fecalith, diffuse fibropurulent exudate outside the RLQ/pelvis, or intraperitoneal abscess
• Weighs equal to or greater than 20kg at time of surgery

Exclusion Criteria

• Pregnant
• Has a penicillin or cephalosporin allergy that is severe or anaphylactic in nature, prohibiting the use of these antibiotics
• Has simple appendicitis
• Undergoes appendectomy following failed or planned medical management of appendicitis
• Has impaired renal function (CrCl <15mL/min)
• Has history of neurological conditions such as encephalopathy, seizures, myoclonus and non-convulsive status epilepticus
• Has a known inability to complete a 30-day postoperative follow up

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins All Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicole M. Chandler, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins All Children's Hospital

Locations

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00323208

Identifier Type: -

Identifier Source: org_study_id