Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)

NCT05784311 | Recruiting Phase 4 DMC

• 1 other identifier: NL82304.058.22
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 11

Brief Summary

The goal of this multicenter randomized controlled trial is to evaluate the additional value of pre-emptive antibiotic treatment on clinically relevant organ/space surgical site infections (OSIs) in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile. The main objectives it aims to answer are:

• To evaluate the effect of pre-emptive antibiotic prophylaxis on clinically relevant OSIs in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile
• To evaluate the effect of pre-emptive antibiotic prophylaxis on other postoperative outcomes (e.g. OSIs, superficial SSIs, POPF, PPH, major morbidity, ICU admission, readmission, length of hospital stay, and mortality).
• To evaluate concordance between perioperatively obtained bile cultures and postoperative cultures from infectious sites, and to evaluate antibiotic sensitivity patterns of the cultured microorganisms. Participants will be randomized with a 1:1 allocation before surgery into the intervention or control group:
• Patients in the intervention group will receive perioperative prophylaxis (similar to the control group) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily.
• Patients in the control group will only receive perioperative prophylaxis (a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4h of surgery), which will be discontinued after surgery.

Conditions

Pancreatic Cancer

Keywords

Antibiotic prophylaxis; Preoperative biliary drainage; Surgical site infection

Outcome Measures

Primary Outcomes (1)

• Rate of clinically relevant organ/space surgical site infection (OSI) between patients with perioperative versus prolonged antibiotic prophylaxis

  A clinically relevant OSI is defined by the following criteria: * A deep surgical site infection involving any part of the abdomen (e.g. organs and/or spaces) other than the surgical incision within 90 days after surgery. * AND Requires radiological, endoscopic or surgical intervention OR therapeutic antibiotics required for an episode of sepsis, defined as two or more SIRS criteria. * AND Organisms isolated from an aseptically obtained culture.

  90 days after surgery

Secondary Outcomes (15)

• The rate of organ/Space Infection (OSI) between patients with perioperative versus prolonged antibiotic prophylaxis

  90 days

• The rate of isolated OSI between patients with perioperative versus prolonged antibiotic prophylaxis

  90 days

• The rate of superficial incisional SSI between patients with perioperative versus prolonged antibiotic prophylaxis

  90 days

• The rate of clinically relevant postoperative pancreatic fistula between patients with perioperative versus prolonged antibiotic prophylaxis

  90 days

• The rate of bile leakage between patients with perioperative versus prolonged antibiotic prophylaxis

  90 days

Other Outcomes (3)

• The percentage of patients with a deviation from antibiotic study protocol

  5 days

• Antibiotic sensitivity patterns of microorganisms cultured from bile cultures and postoperative cultures from infectious sites between patients with perioperative versus prolonged antibiotic prophylaxis

  90 days

• The percentage of concordance of microorganisms in bile and cultures from infectious sites postoperatively

  90 days

Study Arms (2)

Perioperative plus prolonged antibiotic prophylaxis

EXPERIMENTAL

Prolonged prophylaxis: a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4 hours of surgery (perioperative prophylaxis) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily

Drug: Cefuroxime; Drug: Metronidazole

Only perioperative prophylaxis

NO INTERVENTION

Perioperative prophylaxis: a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4 hours of surgery.

Interventions

Cefuroxime DRUG

1500mg IV cefuroxime thrice daily during five days.

Also known as: Zinacef

Perioperative plus prolonged antibiotic prophylaxis

Metronidazole DRUG

500mg IV metronidazole thrice daily during five days.

Also known as: Flagyl

Perioperative plus prolonged antibiotic prophylaxis

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing elective pancreatoduodenectomy with a high risk for contaminated bile defined as patients with preoperative biliary drainage or an ampullary malignancy.
• Age \>18 years

You may not qualify if:

• Pregnancy
• Contraindication for the study antibiotics (e.g. allergy or intolerance)
• Preoperative planned therapeutic antibiotic treatment (i.e. for cholangitis or liver abscesses)
• A reduced renal function, defined as an eGFR of \<60 ml/min/1.73m2 measured on the closest timepoint prior to pancreatoduodenectomy

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (11)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands

NOT YET RECRUITING

Amsterdam University Medical Center

Amsterdam, Netherlands

RECRUITING

Amphia Ziekenhuis

Breda, Netherlands

RECRUITING

Catharina Ziekenhuis

Eindhoven, Netherlands

RECRUITING

Medisch Spectrum Twente

Enschede, Netherlands

RECRUITING

Groningen University Medical Center

Groningen, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, Netherlands

RECRUITING

Radboud University Medical Center

Nijmegen, Netherlands

RECRUITING

Erasmus MC Cancer Institute

Rotterdam, Netherlands

RECRUITING

Regional Academic Cancer Center Utrecht

Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms; Surgical Wound Infection

Interventions

Cefuroxime; Metronidazole

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• J. Sven D. Mieog, MD PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daphne HM Droogh, MD

CONTACT

071 5261334; d.h.m.droogh@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients will be randomized with a 1:1 allocation before surgery into the intervention or control group: * Patients in the intervention group will receive perioperative prophylaxis (similar to the control group) followed by five days of 1500mg IV cefuroxime and 500mg IV metronidazole thrice daily. * Patients in the control group will only receive perioperative prophylaxis (a single dose of 5-7mg/kg gentamicin followed by 2gr IV cefazolin and 500mg IV metronidazole every 4h of surgery), which will be discontinued after surgery.

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: March 24, 2023
• Study Start: March 6, 2023
• Primary Completion: July 1, 2025
• Study Completion: January 1, 2026
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (11)