Laparoscopic Antibiotic Lavage to Prevent Intra-abdominal Abscess Formation in Complicated Appendicitis (ALPACA)

Laparoscopic Antibiotic Lavage to Prevent Intra-abdominal Abscess Formation in Complicated Appendicitis (ALPACA), a Multicenter Single-blinded RCT.

Appendicitis is one of the most common causes of acute surgical admission. Presently, two types of appendicitis are distinguished: complicated and uncomplicated (phlegmonous). Complicated appendicitis (CA) is defined as gangrenous and/or perforated appendicitis and/or appendicitis with an intra-abdominal or pelvic abscess. Laparoscopic appendectomy has become the preferential mode of surgical treatment. However, development of an intra-abdominal abscess (IAA) remains an important and clinically relevant complication following appendectomy, especially in complicated appendicitis. Although patients with complicated appendicitis receive postoperative intravenous antibiotics, the incidence of IAA remains considerable. The reported incidence of IAA in children and adults with CA is 7.9% - 24%. We recently reported an IAA rate of 12.3% after laparoscopic appendectomy for CA in our own institution. Patients with IAA are readmitted and treated with either antibiotics, image-guided percutaneous drainage, surgical reintervention, or a combination of these treatments. Furthermore, IAA represents a considerable burden for the healthcare system with high readmission rates and reinterventions, prolonged hospital stay, and therefore increased medical costs. Intra operative techniques aiming at more effective infection source control represent a clinically relevant area of investigation. Laparoscopic antibiotic lavage represents a promising concept in order to reduce intra-abdominal abscess formation. Antibiotic lavage is mainly known for the treatment of peritoneal dialysis associated peritonitis. Several studies show promising results of antibiotic peritoneal lavage on the incidence of surgical site infections (SSIs) including IAA in patients with CA. However, these studies were retrospective or conducted in a small number of patients who underwent an open appendectomy while high quality randomized controlled trials have not been performed yet.

The aim of the ALPACA study is to evaluate the effect of laparoscopic antibiotic peritoneal lavage with gentamicin / clindamycin for 3 minutes after appendectomy on the incidence of IAA in patients with CA.

Study Overview

• Status: Not yet recruiting
• Conditions: Intra-Abdominal Abscess; Complicated Appendicitis
• Intervention / Treatment: Drug: Laparoscopic antibiotic peritoneal lavage with gentamicin / clindamycin

• Study Type: Interventional
• Enrollment (Estimated): 752
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Emeline Gebro, Master of science degree; Phone Number: +31(0)23 2241685; Email: alpaca@spaarnegasthuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients ≥ 8 years with a preoperative diagnosis of acute appendicitis either with or without clinical or radiological suspicion of CA undergoing a laparoscopic appendectomy for intra-operative confirmed CA that can provide a signed written consent form.

Exclusion Criteria:

• Age under 8 years;
• Not able to give informed consent (language barrier, legally incapable)

• Any contraindication for the use of the study medication:

  • Hypersensitivity to clindamycin or to any of the excipients benzyl alcohol, sodium edetate, water, or to lincomycin;
  • Hypersensitivity to gentamicin or to sodium metabisulfite: particularly in asthmatic patients, this may trigger bronchospasms and anaphylactic shock or to any of the excipients: disodium edetate, sodium hydroxide, sodium metabisulfite (E223), water for injections;

• Severe sepsis defined as sepsis-induced tissue hypoperfusion or organ dysfunction that includes any of the following thought to be caused by the infection:

  • Sepsis-induced hypotension
  • Lactate above upper limits laboratory normal
  • Urine output <0.5 mL/kg/h for more than 2h despite adequate fluid resuscitation
  • Acute lung injury with PaO2/FiO2 <250 in the absence of pneumonia as infection source
  • Acute lung injury with PaO2/FiO2 <200 in the presence of pneumonia as infection source
  • Creatinine >2.0 mg/dL (176.8 μmol/L)
  • Bilirubin >2mg/dL (34.2 μmol/L)
  • Platelet count < 100,000 μL
  • Coagulopathy (international normalized ratio (INR) > 1.5);
• ASA IV score;
• Known malignancy;
• Renal dysfunction (i.e. eGFR ≤ 60);
• Immunocompromised patients (i.e. hematological malignancies, HIV/AIDS, bone marrow transplantation, splenectomy, genetic disorders such as severe combined immunodeficiency, chemotherapy, dialysis, solid organ transplant, and immunosuppressant use (such as corticosteroids in patients with rheumatoid arthritis));
• Pregnancy;
• Known allergies to either gentamicin or clindamycin;
• Known colonization of bacteria resistant to either gentamicin or clindamycin;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group
Experimental: Laparoscopic antibiotic lavage	Drug: Laparoscopic antibiotic peritoneal lavage with gentamicin / clindamycin; Peritoneal antibiotic lavage using a solution of gentamicin/clindamycin in NaCl 0.9%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The incidence of intra-abdominal abscess (IAA)	Within 30 days follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of participants with wound infections measured by tracking any wound complications that these patients have and comparing the incidence between treatment arms		Within 90-days follow-up
The type of treatment for the intra-abdominal abscess, consisting of percutaneous (radiological drainage), surgical drainage, antibiotic treatment or observation only		Within 90-days follow-up
Microbial cultures of intra-operative aspirate, based on cultures		Within 90-days follow-up
Operating time		From the moment of start surgery (the incision) to wound closure.
Readmission rate		Within 90-days follow-up
Reoperation rate		Within 90-days follow-up
Length of stay (including readmission)		Within 90-days follow-up
Adverse events of antibiotic peritoneal lavage		Within 90-days follow-up
Surgical complications according to the Clavien-Dindo classification		Within 90-days follow-up
Mortality		Within 90-days follow-up
Quality of life	Measured by digital questionnaire of EuroQol-5 Dimension (EQ-5D)	Within 90-days follow-up
The number of postoperative consultations will be measured by tracking any postoperative consultation that these patients have and comparing the incidence between treatment arms	Including emergency department visits, telephone consultations and outpatient consultations	Within 90-days follow-up
Cost-effectivity,	Cost-effectivity will be determined by IMTA Productivity Cost Questionnaire (iPCQ)	Within 90-days follow-up
Microbial cultures of postoperative intra-abdominal asbcess, based on cultures		Within 90-days follow-up
Cost-effectivity	The cost-effectivity will be determined by iMTA Medical Consumption Questionnaire	Within 90-days follow-up

Collaborators and Investigators

• Sponsor: Spaarne Gasthuis
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Infections; Digestive System Diseases; Gastrointestinal Diseases; Inflammation; Gastroenteritis; Suppuration; Cecal Diseases; Intraabdominal Infections; Abscess; Appendicitis; Abdominal Abscess; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Synthesis Inhibitors; Anti-Bacterial Agents; Clindamycin; Clindamycin palmitate; Clindamycin phosphate; Gentamicins
• Other Study ID Numbers: 2024-514850-59-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No