Perioperative hydrocortisone treatment in pancreatoduodenectomy – randomised double-blinded placebo-controlled interventional trial (PD-HYDRA)

2024-517877-26-00 Protocol P003623 Phase II and Phase III (Integrated) Ongoing, recruiting

Start 16 Oct 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 14 sites · Protocol P003623

Overview

Sponsor-declared trial summary

Phase Phase II and Phase III (Integrated)
Status Ongoing, recruiting
Participants planned 614
Countries 1
Sites 14

Pancreatic resection

1. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Post-operative pancreatic fistula of grade B or worse within 90 days after surgery (POPF B/C)

Key facts

Sponsor
Universitaetsklinikum Schleswig-Holstein AöR
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Digestive System Diseases [C06]
Trial duration
16 Oct 2025 → ongoing
Decision date (initial)
2025-03-07
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Deutsche Forschungsgemeinschaft (DFG)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

1. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Post-operative pancreatic fistula of grade B or worse within 90 days after surgery (POPF B/C)

Secondary objectives 13

  1. 2. to assess the efficacy of per protocol hydrocortisone infusions in comparison to placebo in high-risk patients with surgery as planned like in the published data. POPF B/C within 90 days after pancreatoduodenectomy
  2. 3. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Overall survival within one year (OS)
  3. 4. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Grade IIIb or worse complication in the Clavien-Dindo Classification (CDC) within 90 days after surgery (CDC IIIb+)
  4. 5. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Grade B or worse postpancreatectomy acute pancreatitis within 90 days after surgery (PPAP B/C)
  5. 6. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Grade C postpancreatectomy haemorrhage within 90 days after surgery (PPH C)
  6. 7. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Grade B or worse delayed gastric emptying within 90 days after surgery (DGE B/C)
  7. 8. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Grade B or worse bile leak within 90 days after surgery (BL B/C)
  8. 9. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Grade B or worse chyle leak within 90 days after surgery (CL B/C)
  9. 10. to assess the efficacy of the treatment strategy with hydrocortisone infusions in comparison to placebo. Completion pancreatectomy within 90 days after surgery
  10. 11. to assess the safety of hydrocortisone infusions in comparison to placebo. Surgical site infection within 90 days after surgery
  11. 12. to assess the safety of hydrocortisone infusions in comparison to placebo. Pneumonia within 90 days after first dose
  12. 13. to assess the safety of hydrocortisone infusions in comparison to placebo. Cholangitis within 90 days after first dose
  13. to assess the safety of hydrocortisone infusions in comparison to placebo. (Serious) adverse events ((S)AE)

Conditions and MedDRA coding

Pancreatic resection

VersionLevelCodeTermSystem organ class
20.0 LLT 10033639 Pancreatic resection 10042613

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. 1. Patients with planned elective PD [pancreatoduodenectomy]; regardless of indication
  2. 2. Male or female patients aged ≥ 18 years without upper age limit
  3. 3. Written informed consent obtained according to international guidelines and local laws
  4. 4. Ability to understand the nature of the trial and the trial related procedures and to comply with them

Exclusion criteria 25

  1. 1. Other perioperatively planned or pre-existing medication with a glucocorticoid in a dose of more than 30mg hydrocortisone-equivalent per day (e.g. for PONV prophylaxis, autoimmune diseases)
  2. 10. Inherited thromboembolic disease (Factor V Leiden Mutation, Prothrombin gene mutation, Protein C-, Protein S-, or antithrombin deficiency),
  3. 11. Myasthenia gravis
  4. 12. Active gastric or duodenal ulcer disease
  5. 13. Active diverticulitis
  6. 14. Active ulcerative colitis
  7. 15. Recent onset (6 months before randomisation) active deep venous thrombosis
  8. 16. Recent onset (6 months before randomisation) thromboembolic disease
  9. 17. GFR < 30 ml/h/1.73 m² as estimated by CKD-EPI Creatinine Equation (2021) (www.kidney.org/professionals/gfr_calculator)
  10. 18. Focal or generalized epilepsy
  11. 19. Untreated overt hypothyroidism (Elevated Thyroid-Stimulating Hormone (TSH) levels and Low Free Thyroxine (FT4) levels)
  12. 2. Vaccination with live vaccine or live attenuated vaccine within the 4 weeks prior to surgery
  13. 20. Pheochromocytoma
  14. 21. Known or persistent abuse of medication, drugs or alcohol
  15. 22. Person who is in a relationship of dependence/employment with the sponsor or the investigator
  16. 23. Current or planned pregnancy, nursing period
  17. 24. For women of childbearing potential failure to use one of the following safe methods of contraception: abstinence from sexual intercourse, female condoms, diaphragm or coil, each used in combination with spermicides; copper intra-uterine device
  18. 3. Known hypersensitivity to the IMP (hydrocortisone or any of the excipients)
  19. 4. Participation in any other interventional clinical trial within the last 30 days prior to surgery
  20. 5. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registries and diagnostic trials is allowed
  21. 6. Patient without legal capacity
  22. 7. Uncontrolled arterial hypertension ESH Grade 3 (blood pressure remains at or above 180/110 mmHg despite treatment)
  23. 8. Chronic heart failure of New York Heart Association (NYHA) class III or IV
  24. 9. Glaucoma
  25. 25. WOCBP using hormonal contraceptives.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. 1. Post-operative pancreatic fistula of grade B or worse within 90 days after surgery (POPF B/C)

Secondary endpoints 13

  1. 2. POPF B/C within 90 days after pancreatoduodenectomy
  2. 3. Overall survival within one year (OS)
  3. 4. Grade IIIb or worse complication in the Clavien-Dindo Classification (CDC) within 90 days after surgery (CDC IIIb+)
  4. 6. Grade C postpancreatectomy haemorrhage within 90 days after surgery (PPH C)
  5. 7. Grade B or worse delayed gastric emptying within 90 days after surgery (DGE B/C)
  6. 8. Grade B or worse bile leak within 90 days after surgery (BL B/C)
  7. 9. Grade B or worse chyle leak within 90 days after surgery (CL B/C)
  8. 10. Completion pancreatectomy within 90 days after surgery
  9. 11. Surgical site infection within 90 days after surgery
  10. 12. Pneumonia within 90 days after first dose
  11. 13. Cholangitis within 90 days after first dose
  12. (Serious) adverse events ((S)AE)
  13. 5. Grade B or worse postpancreatectomy acute pancreatitis within 90 days after surgery (PPAP B/C)

Investigational products

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

Test 1

HYDROCORTISON Pfizer 100 mg sine Pulver und Lösungsmittel zur Herstellung einer Injektions- oder Infusionslösung

PRD4259142 · Product

Active substance
Hydrocortisone
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INFUSION
Max daily dose
300 mg milligram(s)
Max total dose
900 mg milligram(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
H02AB09 — HYDROCORTISONE
Marketing authorisation
6177448.00.00
MA holder
PFIZER PHARMA GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Sodium Chloride

SUB12581MIG · Substance

Active substance
Sodium Chloride
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INFUSION
Max daily dose
300 ml millilitre(s)
Max total dose
900 ml millilitre(s)
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Schleswig-Holstein AöR

11 Total trials 8 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
Universitaetsklinikum Schleswig-Holstein AöR
Address
Ratzeburger Allee 160
City
Luebeck
Postcode
23538
Country
Germany

Scientific contact point

Organisation
Universitaetsklinikum Schleswig-Holstein AöR
Contact name
Coordinating Investigator

Public contact point

Organisation
Universitaetsklinikum Schleswig-Holstein AöR
Contact name
Project Management

Third parties 3

OrganisationCity, countryDuties
Medical Center - University Of Freiburg
ORG-100010322
 Freiburg Im Breisgau, Germany Other
Medical Center - University Of Freiburg
ORG-100010322
 Freiburg Im Breisgau, Germany On site monitoring, Code 11, Code 12, Code 5, Data management, E-data capture, Code 8
Medical Center - University Of Freiburg
ORG-100010322
 Freiburg Im Breisgau, Germany Other

Locations

1 EU/EEA country · 14 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Ongoing, recruiting 614 14
Rest of world — 0 —

Investigational sites

Germany

14 sites · Ongoing, recruiting
University Medical Center Hamburg-Eppendorf
Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Martinistrasse 52, Eppendorf, Hamburg
Klinikum der Universitaet Muenchen AöR
Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Marchioninistrasse 15, Hadern, Munich
Heidelberg University
Chirurgische Klinik, Theodor-Kutzer-Ufer 1-3, Wohlgelegen, Mannheim
University Hospital Cologne AöR
Klinik für Allgemein-, Viszeral-, Tumor- und Transplantationschirurgie, Kerpener Strasse 62, Lindenthal, Cologne
Universitaetsmedizin Goettingen
Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Robert-Koch-Strasse 40, Weende, Goettingen
Universitaetsklinikum Aachen AöR
Klinik und Lehrstuhl für Allgemein-, Viszeral- und Transplantationschirurgie, Pauwelsstrasse 30, 52074, Aachen
Universitaetsklinikum Heidelberg AöR
Klinik für Allgemein- Viszeral und Transplantationschirurgie, Im Neuenheimer Feld 420, 69120, Heidelberg
Universitaetsklinikum Regensburg AöR
Klinik und Poliklinik für Chirurgie, Franz-Josef-Strauss-Allee 11, Grass-Oberisling, Regensburg
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
Klinik und Poliklinik für Chirurgie, Ismaninger Strasse 22, Au-Haidhausen, Munich
St. Josef-Hospital
Klinik für Allgemein- und Viszeralchirurgie, Gudrunstrasse 56, Grumme, Bochum
Medical Center - University Of Freiburg
Klinik für Allgemein- und Viszeralchirurgie, Hugstetter Strasse 55, Stuehlinger, Freiburg Im Breisgau
Universitaetsklinikum Schleswig-Holstein AöR
Klinik für Chirurgie, Ratzeburger Allee 160, 23538, Luebeck
Charite Universitaetsmedizin Berlin KöR
Chirurgische Klinik, Augustenburger Platz 1, Wedding, Berlin
Justus-Liebig-Universitaet Giessen
Klinik für Allgemein-, Viszeral-, Thorax-, und Transplantationschirurgie, Rudolf-Buchheim-Strasse 7, 35392, Giessen

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Germany 2025-10-16 2025-11-25

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.

TypeTitleVersion
Protocol (for publication) D1_Protocol_V3_20250612_public 3
Recruitment arrangements (for publication) K1_recruitment arrangements_public 1
Subject information and informed consent form (for publication) L1_SIS and ICF Hauptstudie_V2_20250221_public 2
Subject information and informed consent form (for publication) L1_SIS and ICF Hauptstudie_V2_20250221_tc 2
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Hydrocortison 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_EN_public 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_EN_V2_20250221_public 2
Synopsis of the protocol (for publication) D1_Protocol Synopsis_EN_V3_20250613_Final 3

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-12-20 Germany Acceptable
2025-03-05
 2025-03-07
2 SUBSTANTIAL MODIFICATION SM-1 2025-06-16 Germany Acceptable
2025-07-10
 2025-07-10

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