(SPARROW) Standard versus Pre-emptive Antibiotic Treatment to Reduce the Rate of Infectious Outcomes after Whipple’s procedure (SPARROW): a multicenter, randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Leiden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

6 Mar 2023 → ongoing

Decision date (initial)

2024-06-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMW

External identifiers

EU CT number

2024-510766-16-00

EudraCT number

2022-003217-11

ClinicalTrials.gov

NCT05784311

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Prophylaxis

The primary endpoint is the occurrence of a clinically relevant OSI and must meet the following criteria (based on the CDCdefinition):
• A deep surgical site infection involving any part of the abdomen (e.g. organs and/or spaces) other than the surgical incision within90 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.

Secondary objectives 19

1. OSI defined by the CDC definition within 90 days after surgery.
2. Isolated OSI defined as an OSI without concurrent anastomotic leakage (pancreatojejunostomy, hepaticojejunostomy orgastrojejunostomy). The concept of an isolated OSI is used to separately classify abdominal infections without concurrentanastomotic leakage.
3. Superficial incisional SSI: defined according to the CDC definition: a superficial surgical site infection occurring within 30 days aftersurgery which involves superficial or deep soft tissue (skin, muscle or fascia, but no intra-abdominal tissue), and at least one of thefollowing criteria is present: - Purulent drainage from the incision or subcutaneous tissue. - Isolation of microorganisms from an aseptically obtained culture of fluid or tissue from the superficial incision of subcutaneoustissue. - Superficial infections of the skin or subcutaneous tissue which is deliberately opened by a surgeon or attending physician OR at least one of the following signs are present: localizes pain, tenderness, swelling, heat or fever >38 degrees).
4. Rate of clinically relevant postoperative pancreatic fistula (grade B or C defined according to the ISGPS definition.
5. Rate of bile and enteric leakage according to the ISGLS definition.
6. Rate of postpancreatectomy hemorrhage according to the ISGPS definition.
7. Rate of delayed gastric emptying according to the ISGPS definition.
8. Rate of chyle leak according to the ISGPS definition.
9. Rate of postoperative bacteraemia (defined as a positive blood culture)
10. Rate of Clostridium difficile infection
11. Rate of major complications, defined as a Clavien-Dindo score of ≥III.
12. Reintervention during admission (either radiological, surgical or endoscopic).
13. ICU admission within 90 days after surgery.
14. Length of hospital stay in days.
15. Readmission within 90 days after surgery.
16. In-hospital and 90-day mortality.
17. Switch of postoperative antibiotics (including reason for deviation from antibiotic protocol).
18. Antibiotic sensitivity patterns in bile cultures and cultures from surgical sites.
19. Concordance of microorganisms in bile and surgical site cultures.

Conditions and MedDRA coding

Pancreatoduodenectomy with a high risk for contaminated bile

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Central Committee On Research Involving Human Subjects, METC Leiden Den Haag Delft

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

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

Exclusion criteria 5

1. Pregnancy
2. Contraindication for the study antibiotics (e.g. allergy or intolerance)
3. Indication for endocarditis prophylaxis
4. Preoperative planned therapeutic antibiotic treatment after surgery (i.e. for cholangitis or liver abscesses)
5. A reduced renal function, defined as a eGFR of <60 ml/min/1.73m2 and measured on a the closest timepoint prior to pancreatoduodenectomy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the additional value of pre-emptive antibiotic prophylaxis on clinically relevant OSIs in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile (patients with preoperative biliary drainage or an ampullary malignancy).

Secondary endpoints 19

1. Rate of OSIs according to the CDC definition
2. Rate of isolated OSIs (OSIs without concurrent anastomotic leak)
3. Rate of superficial SSIs (wound infections)
4. Rate of clinically relevant POPF
5. Rate of bile and enteric leak
6. Rate of post pancreatectomy hemorrhage
7. Rate of delayed gastric emptying
8. Rate of postoperative bacteraemia
9. Rate of Clostridium difficile infection
10. Rate of major complications (Clavien-Dindo ≥III)
11. Reintervention (either surgical, radiological of endoscopic)
12. ICU admission
13. Length of hospital stay
14. Readmission
15. Mortality
16. Switch of postoperative antibiotics
17. Antibiotic sensitivity patterns in bile cultures and cultures from surgical sites
18. Concordance of microorganisms in bile and surgical site cultures
19. Rate of chyle leak according to the ISGPS definition.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Clinical Research Center, dept. of Surgery

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

Clinical Research Center, dept. of Surgery

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications