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Antibiotic Instillation in Appendicitis

Antibiotic Instillation in Acute Complex Appendicitis for Prevention of Deep Space Surgical Site Infections

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05470517
Enrollment
190
Registered
2022-07-22
Start date
2023-01-05
Completion date
2024-03-20
Last updated
2025-03-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Appendicitis, Complicated Appendicitis

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.

Interventions

DRUGCeftriaxone

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.

PROCEDUREIntra-peritoneal Fluid Aspiration

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

Sponsors

Johns Hopkins All Children's Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)

Masking description

The surgeon and team administering the treatment will not be blinded; however, patients, patients' families, and hospital caregivers outside of the operating room will be blinded to the treatment.

Intervention model description

Single-blinded randomized controlled pilot phase 2 study

Eligibility

Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Feasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Eligible Participants Who Agree to ParticipateUp to 30 days postoperativelyThe study will be deemed feasible if \>50% of potential participants agree to participate. This benchmark is based on a previous similar study completed in this population.
Feasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Randomized Participants Who Complete All Intervention Sessions and Measurement Time PointsUp to 30 days postoperativelyThe study will be deemed feasible if at least 75% of randomized participants complete all intervention sessions and measurement time points per study protocol. This benchmark is based on a previous similar study completed in this population.
Safety of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Number of Adverse EventsUp to 30 days postoperativelySafety will be determined by adverse events in all participants.

Countries

United States

Participant flow

Pre-assignment details

Those eligible preoperatively (n=337) were approached for consent with the caveat that they are eligible intraoperatively (complicated appendicitis). The number of patients who were consented (190) is not the same as the number of patients who were randomized (32). The remaining 158 eligible participants were not randomized due to intraoperative findings (n=156) and screen failures (n=2).

Participants by arm

ArmCount
Standard of Care (Arm A)
Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy. Intra-peritoneal Fluid Aspiration: Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy.
16
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) 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. Intra-peritoneal Fluid Aspiration: Intra-operative aspiration of intra-peritoneal fluid after successful appendectomy.
16
Total32

Baseline characteristics

CharacteristicStandard of Care and Antibiotic Instillation (Arm B)TotalStandard of Care (Arm A)
Age, Continuous11.58 years
STANDARD_DEVIATION 3.96
11.77 years
STANDARD_DEVIATION 3.81
11.96 years
STANDARD_DEVIATION 3.77
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants13 Participants7 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
8 Participants16 Participants8 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants3 Participants1 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Black or African American
1 Participants1 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants9 Participants6 Participants
Race (NIH/OMB)
White
12 Participants21 Participants9 Participants
Sex: Female, Male
Female
5 Participants10 Participants5 Participants
Sex: Female, Male
Male
11 Participants22 Participants11 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 160 / 16
other
Total, other adverse events
9 / 168 / 16
serious
Total, serious adverse events
0 / 160 / 16

Outcome results

Primary

Feasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Eligible Participants Who Agree to Participate

The study will be deemed feasible if \>50% of potential participants agree to participate. This benchmark is based on a previous similar study completed in this population.

Time frame: Up to 30 days postoperatively

Population: Patients With Appendicitis Eligible for Study

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
Number of Patients With Appendicitis Eligible for StudyFeasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Eligible Participants Who Agree to ParticipateNumber of Patients Eligible who Declined Study Participation147 Participants
Number of Patients With Appendicitis Eligible for StudyFeasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Eligible Participants Who Agree to ParticipateTotal number of Eligible Patients who Agreed to Participate190 Participants
Primary

Feasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Randomized Participants Who Complete All Intervention Sessions and Measurement Time Points

The study will be deemed feasible if at least 75% of randomized participants complete all intervention sessions and measurement time points per study protocol. This benchmark is based on a previous similar study completed in this population.

Time frame: Up to 30 days postoperatively

ArmMeasureValue (NUMBER)
Number of Patients With Appendicitis Eligible for StudyFeasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Randomized Participants Who Complete All Intervention Sessions and Measurement Time Points100 percentage of participants
Standard of Care and Antibiotic Instillation (Arm B)Feasibility of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Percentage of Randomized Participants Who Complete All Intervention Sessions and Measurement Time Points81 percentage of participants
Primary

Safety of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Number of Adverse Events

Safety will be determined by adverse events in all participants.

Time frame: Up to 30 days postoperatively

ArmMeasureValue (NUMBER)
Number of Patients With Appendicitis Eligible for StudySafety of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Number of Adverse Events11 adverse events
Standard of Care and Antibiotic Instillation (Arm B)Safety of the Use of Antibiotic Solution Instillation Following Intraoperative Diagnosis of Complex Appendicitis as Assessed by Number of Adverse Events17 adverse events

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026