Trial Title:
Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)
NCT ID:
NCT05784311
Condition:
Pancreatic Cancer
Conditions: Official terms:
Metronidazole
Cefuroxime
Cefuroxime axetil
Conditions: Keywords:
Antibiotic prophylaxis
Preoperative biliary drainage
Surgical site infection
Study type:
Interventional
Study phase:
Phase 4
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cefuroxime
Description:
1500mg IV cefuroxime thrice daily during five days.
Arm group label:
Perioperative plus prolonged antibiotic prophylaxis
Other name:
Zinacef
Intervention type:
Drug
Intervention name:
Metronidazole
Description:
500mg IV metronidazole thrice daily during five days.
Arm group label:
Perioperative plus prolonged antibiotic prophylaxis
Other name:
Flagyl
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.
Detailed description:
Rationale: The additional value of pre-emptive antibiotic treatment after
pancreatoduodenectomy is undetermined as previous research reported conflicting results
regarding infectious complications. Prolonged antibiotic prophylaxis (formally
pre-emptive antibiotic treatment) after pancreatoduodenectomy might reduce the rate of
surgical site infections in patients with a high risk for contaminated bile
(predominantly patients with preoperative biliary drainage or an ampullary malignancy).
Current national and international guidelines lack clear recommendations regarding
pre-emptive antibiotic treatment leading to substantially varying antibiotic prophylactic
regimes between institutes.
Objective: This trial evaluates 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.
Study design: This multicenter, randomized controlled, superiority trial compares
perioperative versus pre-emptive antibiotic treatment during five postoperative days
after pancreatoduodenectomy in patients with a high risk for contaminated bile.
Study population: Adult patients undergoing pancreatoduodenectomy with a high risk for
contaminated bile (patients with preoperative biliary drainage or an ampullary
malignancy). Patients with a contraindication for the study antibiotics or a preoperative
indication for antibiotics (e.g. cholangitis of preoperative abscesses) are excluded.
Intervention: Participants will be randomized to either perioperative prophylaxis
(cefazolin, metronidazole and a single dose of 5-7mg/kg gentamicin, control arm) or
additional cefuroxime and metronidazole for five postoperative days (experimental arm).
Main study endpoints: The primary endpoint are organ/space infections (OSIs) within 90
days after surgery requiring a therapeutic intervention. Secondary endpoints are OSIs,
isolated OSIs, wound infections, postoperative pancreatic fistula, bile or enteric
anastomotic leakage, post pancreatectomy hemorrhage, delayed gastric emptying,
bacteremia, Clostridium difficile infection, major morbidity (Clavien-Dindo ≥III),
reintervention, ICU admission, length of hospital stay, readmission, and in-hospital and
90-day mortality. Besides, switch of postoperative antibiotics, antibiotic sensitivity
patterns and concordance between perioperative bile and postoperative surgical site
cultures are analyzed.
Sample size: The sample size is calculated for superiority to achieve an OSI difference
of 15% (40% vs 25%). With a 80% power (1-β) and a two-sided significance level (α) of
5.0%, a sample of 304 evaluable patients is required for superiority. Assuming a 3%
non-resection rate due to metastatic disease and a 3% loss-of-follow-up rate, an expected
number of 322 included patients are needed to reach the sample size of 304 evaluable
patients to demonstrate superiority for the intervention.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
90 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Leiden University Medical Center
Address:
City:
Leiden
Zip:
2333 ZA
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Daphne HM Droogh, MD
Phone:
071 5261334
Email:
d.h.m.droogh@lumc.nl
Contact backup:
Last name:
Daphne HM Droogh, MD
Contact backup:
Last name:
J. Sven D. Mieog, MD PhD
Facility:
Name:
Amsterdam University Medical Center
Address:
City:
Amsterdam
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Marc GH Besselink, Prof. Dr
Contact backup:
Last name:
Marc GH Besselink, Prof. Dr.
Facility:
Name:
Amphia Ziekenhuis
Address:
City:
Breda
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Jan H Wijsman, MD PhD
Facility:
Name:
Jeroen Bosch Ziekenhuis
Address:
City:
Den Bosch
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Koop Bosscha, MD
Facility:
Name:
Catharina Ziekenhuis
Address:
City:
Eindhoven
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Misha DP Luyer, MD PhD
Facility:
Name:
Medisch Spectrum Twente
Address:
City:
Enschede
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Daan J Lips, MD PhD
Facility:
Name:
Groningen University Medical Center
Address:
City:
Groningen
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Frederik JH Hoogwater, MD PhD
Facility:
Name:
Maastricht University Medical Center
Address:
City:
Maastricht
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Stefan AW Bouwense, MD PhD
Facility:
Name:
Radboud University Medical Center
Address:
City:
Nijmegen
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Martijn Stommel, MD PhD
Facility:
Name:
Erasmus MC Cancer Institute
Address:
City:
Rotterdam
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Bas Groot Koerkamp, Prof. Dr.
Facility:
Name:
Regional Academic Cancer Center Utrecht
Address:
City:
Utrecht
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Hjalmar C van Santvoort, Prof. Dr
Contact backup:
Last name:
Hjalmar C van Santvoort, Prof. Dr.
Start date:
March 6, 2023
Completion date:
January 2026
Lead sponsor:
Agency:
Leiden University Medical Center
Agency class:
Other
Source:
Leiden University Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05784311
