E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pancreatic head malignancy |
Pancreaskopcarcinoom |
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E.1.1.1 | Medical condition in easily understood language |
Pancreatic cancer |
Alvleesklierkanker |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033614 |
E.1.2 | Term | Pancreatic carcinoma resectable |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026319 |
E.1.2 | Term | Malignant neoplasm of pancreatic duct |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 27.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008597 |
E.1.2 | Term | Cholangiocarcinoma resectable |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This trial evaluates the additional value of pre-emptive antibiotic treatment on OSIs (organ/space infection) in patients undergoing pancreatoduodenectomy with a high risk for contaminated bile. |
Deze studie evalueert de toegevoegde waarde van pre-emptieve antibiotica op abdominale infecties in patiënten die met een hoog risico op gecontamineerde gal een pancreatoduodenectomie ondergaan. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the following secondary endpoints comparing perioperative antibiotic prophylaxis versus pre-emptive antibiotic treatment: • Rate of (isolated) OSIs • Rate of superficial SSIs (wound infections) • Rate of clinically relevant POPF • Rate of bile and enteric leakage • Rate of delayed gastric emptying • Rate of postoperative bacteraemia • Rate of major complications (Clavien-Dindo ≥III) • Reintervention (either surgical, radiological of endoscopic) • ICU admission • Length of hospital stay • Readmission • Mortality • Switch of postoperative antibiotics • Antibiotic sensitivity patterns in bile cultures and cultures from surgical sites • Concordance of microorganisms in bile and surgical site cultures
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Het effect van perioperatieve versus pre-emptieve antibioticaprofylaxe te evalueren op de volgende eindpunten: • Aantal (geisoleerde) abdominale infecties • Aantal oppervlakkige chirurgische infecties (wondinfecties) • Klinisch relevante pancreasfistels (graad B of C) • Gallekkage (ISGLS definitie) • Vertraagde maagontlediging (ISGPS definitie) • Postoperatieve bacteriemie • Majeure complicaties (Clavien-Dindo ≥III) • Reïnterventie gedurende opname (radiologisch, chirurgisch of endoscopisch) • IC opname • Opnameduur • Heropnames binnen drie maanden na chirurgie • Mortaliteit • Verandering van postoperatieve antibiotica • Antibioticagevoeligheid in galkweken en postoperatieve kweken • Overeenkomst van micro-organismen in gal- en postoperatieve kweken |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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• Patiënten met een indicatie voor pancreatoduodenectomie met een hoog risico om de operatie te ondergaan met gecontamineerde gal, gedefinieerd als patiënten met een preoperatieve biliaire stent of een papilcarcinoom. • Leeftijd >18 jaar
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E.4 | Principal 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)
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• Zwangerschap • Contra-indicatie voor de studieantibiotica (bijvoorbeeld allergie of intoleratie) • Preoperatieve therapeutische indicatie voor antibiotica (bijvoorbeeld cholangitis of leverabcessen) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the occurrence of an abdominal infection defined as an organ/space infection (OSI): a deep surgical site infection. The OSI is defined by the following criteria, based on the CDC definition: • The infection involves any part of the abdomen (e.g. organs and/or spaces) other than the incision opened or manipulated during the surgical procedure • AND Organisms were isolated from an aseptically obtained culture of fluid or tissue in the organ and/or space. • AND The infection occurs within 90 days after the surgical procedure • AND Evaluated by the Central Review Committee |
De primaire uitkomstmaat is het voorkomen van een abdominale infectie, gedefinieerd als een infectie in de abdominale ruimte of van een abdominaal orgaan: een diepe chirurgische infectie. De abdominale infectie wordt als volgt gedefinieerd: • The infectie bevindt zich in de abdominale ruimte of een abdominaal orgaan, anders dat de incisie van de operatie • EN Er zijn micro-organismen geïsoleerd vanuit een aseptisch uitgevoerde kweek vanuit de abdominale ruimte of van een abdominaal orgaan. • EN The infectie ontstaat binnen 90 dagen na de operatie • EN Is geëvalueerd door de centrale review commissie
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
90 days after surgery |
90 dagen na de operatie |
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E.5.2 | Secondary end point(s) |
The following secondary endpoints will be evaluated between patients receiving perioperative prophylaxis versus pre-emptive antibiotic treatment: • Isolated OSI: defined as an OSI without concurrent anastomotic leakage (pancreatojejunostomy, hepaticojejunostomy or gastrojejunostomy) within 90 days after surgery. • Surgical site infection (SSI): defined as a superficial surgical site infection: - 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 subcutaneous tissue. - 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). • Rate of clinically relevant postoperative pancreatic fistula (grade B or C defined according to the ISGPS definition • Rate of bile and enteric leakage according to the ISGLS definition • Rate of delayed gastric emptying according to the ISGPS definition • Rate of postoperative bacteremia (defined as a positive blood culture) • Rate of major complications, defined as a Clavien-Dindo score of ≥III • Reintervention during admission (either radiological, surgical or endoscopic) • Single or multi-organ failure during admission • ICU admission • Length of hospital stay in days • Readmission within 90 days after surgery • In-hospital and 30-day mortality • Switch of postoperative antibiotics (including reason for deviation from antibiotic protocol) • Antibiotic sensitivity patterns in bile cultures and cultures from surgical sites • Concordance of microorganisms in bile and surgical site cultures |
• Geïsoleerde abdominale infecties (OSI): een OSI zonder gelijktijdige naadlekkage (van de pancreatojejunostomie, hepatojejunostomie of gastrojejunostomie binnen 90 dagen na de operatie. • Oppervlakkige chirurgische infectie (= wondinfectie), gedefinieerd als: - Purulente drainage vanuit de incisie of het subcutane weefsel - Isolatie van micro-organismen vanuit een aseptisch uitgevoerde kweek vanuit de incisie of subcutane weefsel - Wondinfecties welke zijn ontlast door een chirurg of arts OF een van de volgende symptomen zijn aanwezig: lokale pijn, zwelling, erytheem of koorts >38 graden • Klinisch relevante pancreasfistels (graad B of C) • Gallekkage (ISGLS definitie) • Vertraagde maagontlediging (ISGPS definitie) • Postoperatieve bacteriemie • Majeure complicaties (Clavien-Dindo ≥III) • Reïnterventie gedurende opname (radiologisch, chirurgisch of endoscopisch) • Orgaanfalen • Heropnames binnen drie maanden na chirurgie • Mortaliteit binnen het ziekenhuis en binnen 90 dagen na de operatie • Verandering van postoperatieve antibiotica (inclusief reden van afwijken van het protocol) • Antibioticagevoeligheid in galkweken en postoperatieve kweken • Overeenkomst van micro-organismen in gal- en postoperatieve kweken |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
30 days after surgery unless indicated otherwise |
30 dagen na de operatie tenzij anders aangegeven |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Geen interventie |
No intervention |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject (90 days after surgery) |
Laatste bezoek van de laatste deelnemer (90 dagen na de operatie) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |