Postoperative Anti-infective Strategy Following Pancreaticoduodenectomy in Patients With Preoperative Biliary Stent

NCT ID: NCT06123169

Last Updated: 2023-11-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 326 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2026-06-30

Brief Summary

The main objective of the study is to compare 2 broad-spectrum antibiotic (Piperacillin / Tazobactam) treatment modalities, following pancreaticoduodenectomy in patients with preoperative biliary stent, to demonstrate the superiority of a 5-day post-operative antibiotic therapy to antibiotic prophylaxis on the occurrence of surgical site infections (SSI)

Detailed Description

Despite cumulative efforts in surgery and perioperative management, the morbi-mortality rates of pancreatoduodenectomy (PD) remain high. The most frequent complications were sepsis and infectious complications 44%, hemorrhagic complications 36.6%, pulmonary complications 35.2%, shock 29.8% and pancreatic fistula 27.9%.

PD is a technically complex procedure with substantial associated morbidity and mortality. Infectious complications have been reported to occur in as many as 30% of patients following open PD.

Biliary colonization that arises from preoperative procedures for biliary drainage closely predicts infectious complications following PD. Besides biliary intervention, nutritional reserve and biliary or pancreatic anastomotic leaks are common factors linked to developing infectious complications following PD.

D'Angelica et al. Recently demonstrated the superiority of Piperacillin-tazobactam compared with cefoxitin as antimicrobial prophylaxis for PD: a randomized clinical trial in JAMA, with a significant reduction of postoperative SSI rate.

One of the main risk factors for infectious complications and especially surgical site infections, but also post-operative pancreatic fistula is bacteriobilia, defined by the bile contamination by microorganism(s) related to preoperative biliary drainage.

A significant decrease in all-type SSI and organ-space SSI with Broad spectrum antibiotics was observed after open PD, as reported by Kone et al. or De Grandi et al. According to Kone et al. on subgroup analysis, only patients with preoperative biliary stents and/ or jaundice (61% of PD patients) had an association between Broad-abx and decreased SSI. Numbered of surgeons modified their antibiotic usage in this setting of preoperative biliary drainage, as we also observed in France, where more than 50% prescribed a broad spectrum antibiotherapy intraoperatively only (antibioprophylaxis) or for 3 to 5 days.

The aim of this study is to determine whether a prophylactic treatment used only during surgery, or for 5 days with this treatment, in the clinical context of PD after biliary drainage, is effective in reducing surgical complications, particularly infectious ones.

Such results could reduce the need for prolonged anti-infectious treatments and reoperations (surgical and radiological). Hospital stays could also be shortened, with a positive impact on your quality of life.

Conditions

Pancreaticoduodenectomy; Antibiotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Broad spectrum antibioprophylaxis

Antibioprophylaxis with Piperacillin-tazobactam during DPC.

Group Type: ACTIVE_COMPARATOR

Antibioprophylaxis (Piperacillin-tazobactam)

Intervention Type: DRUG

antibiotic prophylaxis during surgery

Broad spectrum antibiotherapy

5 days Antibiotherapy (Piperacillin-tazobactam) from surgery.

Group Type: EXPERIMENTAL

5 days Antibiotherapy (Piperacillin-tazobactam)

Intervention Type: DRUG

5 days Antibiotherapy from surgery

Interventions

Antibioprophylaxis (Piperacillin-tazobactam)

antibiotic prophylaxis during surgery

Intervention Type: DRUG

5 days Antibiotherapy (Piperacillin-tazobactam)

5 days Antibiotherapy from surgery

Intervention Type: DRUG

Other Intervention Names

Control arm; experimental arm

Eligibility Criteria

Inclusion Criteria

• Planned pancreaticoduodenectomy for periampullary neoplasms
• Endoscopic or radiological pre-operative biliary drainage
• Age ≥ 18 years old
• Patient able to comply with the study protocol, in the investigator's judgment
• Patient affiliated with, or beneficiary of a social security (national health insurance) category
• Person of full age having read and understood the information letter and signed the consent form
• Women of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile) with hightly effective contraception (Cf. CTFG) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system ( IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence) since 1 month and during the duration of the study and a negative blood pregnancy test by beta-HCG at inclusion.
• Women permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
• Postmenopausal women: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

Exclusion Criteria

• Contraindication to PIPERACILLIN/TAZOBACTAM PANPHARMA 4g / 500mg powder for solution for injection in accordance with its SmPC
• Patients allergic to beta-lactam antibiotics
• Others pancreatic resection
• Absence of preoperative biliary drainage
• Surgical or anaesthesiological contra-indications:
• non-controlled congestive heart failure - non-treated angina - recent myocardial infarction (in the previous year) - non-controlled AHT (SBP >160 mm or DBP > 100 mm, despite optimal drug treatment), long QT
• major non-controlled infection
• severe liver failure
• Medical, geographical, sociological, psychological or legal conditions that would not permit the patient to complete the study or sign informed consent
• Any significant disease, which, in the investigator's opinion, would exclude the patient from the study
• Pregnant or parturient or breastfeeding woman or absence of contraceptionn
• Person deprived of liberty by administrative or judicial decision or person placed under judicial protection, under guardianship or supervision
• Simultaneous participation in another interventional research with the same primary endpoint.

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

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Lilian Schwarz

Role: CONTACT

lilian.schwarz@chu-rouen.fr

0232888416 ext. +33

Julie Rondeaux, PhD

Role: CONTACT

julie.rondeaux@chu-rouen.fr

0232885427 ext. +33

References

Schwarz L, Gillibert A, Rondeaux J, Lacroix E, Sa Cunha A, Joannes-Boyau O. Study protocol of the FRENCH24-ANIS study: postoperative anti-infective strategy following pancreaticoduodenectomy in patients with preoperative biliary stents-an intergroup FRENCH-ACHBT-SFAR prospective randomized controlled trial. BMC Surg. 2024 Aug 22;24(1):237. doi: 10.1186/s12893-024-02507-y.

Reference Type: DERIVED

PMID: 39169298 (View on PubMed)

Other Identifiers

2021-006991-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2020/0423/HP

Identifier Type: -

Identifier Source: org_study_id