Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
232
Countries
2
Sites
16
Predicted severe acute pancreatitis
Overall study hypothesis Based on the literature, there seems to be a relation in AP between (hyper)inflammation, SIRS, new onset of organ failure and mortality. Omega3 fatty acids seem to have clinical beneficial effects through immunomodulation, supported by the decreased inflammatory biomarkers in patients with AP. …
Key facts
- Sponsor
- Stichting Radboud University Medical Center
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06]
- Trial duration
- 9 May 2022 → ongoing
- Decision date (initial)
- 2024-11-18
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2023-505220-57-03
- EudraCT number
- 2022-000474-26
- ISRCTN
- ISRCTN13860158
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
Overall study hypothesis
Based on the literature, there seems to be a relation in AP between (hyper)inflammation, SIRS, new onset of organ failure and mortality. Omega3 fatty acids seem to have clinical beneficial effects through immunomodulation, supported by the decreased inflammatory biomarkers in patients with AP. Therefore, the following hypothesis was formulated:
Early intravenous administration of Omega3 fatty acids reduces the composite endpoint of new onset organ failure and/or mortality in patients with predicted SAP.
Overall study objective
To investigate whether early intravenous administration of Omega3 fatty acids compared to standard medical care has beneficial effects and reduces the combined endpoint of new onset organ failure and/or mortality in patients with predicted SAP.
Objectives randomized controlled trial
Secondary aims in this study are to investigate the effect of Omega3 fatty acids supplementation on i.e. the separate endpoints of the combined endpoint, (serious) adverse events, hospital and ICU stay, need for interventions, hospital costs, and quality of life.
Conditions and MedDRA coding
Predicted severe acute pancreatitis
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | PLANCTON trial Pancreatitis and early omega-3-fatty acid infusion for reduction of organ failure and mortality: a multicenter randomized controlled trial
|
Randomised Controlled | None | Control arm: Standard medical care Intervention arm: Early (ideally within 24 hours after diagnosis acute pancreatitis) administration of Omegaven. Treatment for a maxium of 7 days. 2ml/kg/day in 14 hours. |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-505220-57-00 | Pancreatitis and early omega-3-fatty acid infusion for reduction of organ failure and mortality: a multicenter randomized controlled trial (PLANCTON). | Stichting Radboud University Medical Center |
| 2023-505220-57-02 | Pancreatitis and early omega-3-fatty acid infusion for reduction of organ failure and mortality: a multicenter randomized controlled trial (PLANCTON). | Stichting Radboud University Medical Center |
| 2023-505220-57-01 | Pancreatitis and early omega-3-fatty acid infusion for reduction of organ failure and mortality: a multicenter randomized controlled trial (PLANCTON). | Stichting Radboud University Medical Center |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Predicted severe AP (The diagnosis of acute pancreatitis and one or more of the following, within 24hrs: 1. APACHE-II score above 7 2. Modified Glasgow score above 2 3. CRP-level above 150 mg per L)
- minimum of 18 years old
- First episode of AP
- less than 24 hours after diagnosis of AP
- less than 72 hours after onset of symptoms of AP
- Able to read and or understand the study procedures
- Able to give informed consent (or their legal representatives)
- Definitions: Acute pancreatitis: at least 2 of these 3 features11: 1. Upper abdominal pain 2. Serum lipase and or amylase levels 3 times the upper level of normal 3. Characteristic findings of AP on contrast enhanced computed tomography scan (CECT). Usually, no CECT imaging is needed as the diagnosis can be made with the findings under 1 and 2
Exclusion criteria 17
- Intake of any omega3 fatty acids-, krill and or algae supplements in the week prior to complaints
- Participation in another intervention study for AP
- Organ failure on admission (Modified Marshall score more than 2)
- Recurrent pancreatitis
- Chronic pancreatitis (Defined by the MANNHEIM criteria)
- Known allergy to fish oil, seafood, soja or egg products
- History or existing hyperlipidemia (laboratory proven triglycerides more than 10.0 mmol per litre)
- History of (severe) liver failure. (Impaired lipid metabolism may lead to accumulation of fatty acids in the blood, increasing risk of adverse events) Based on coagulation Factor V level or INR more than 3 (without anti-coagulation by vitamine K)
- Ketoacidosis
- Acute thrombo-embolic disease
- Pregnancy or lactation
- Recent (less than 6 months) myocardial infarction or stroke
- Known coagulations disorders (e.g. Factor V Leiden, thrombocytopenia, etc.)
- Pancreatitis due to a (suspected) periampullary or ampullary or bile duct malignancy
- Other known or suspected malignancy that may interfere with the outcome(s) and or execution of the PLANCTON trial
- Post ERCP-pancreatitis due to a (suspected) malignancy
- Patient is classified as moribund or expected to die within 24hours The intervention will not be able to affect this patient and is therefore useless to expose these patients.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Endpoints will be evaluated after the 180 days study period. The primary endpoint is a composite endpoint of new organ failure (cardiovascular, pulmonary or renal) and mortality. Definitions New onset organ failure is defined as organ failure that was not present at randomization. Organ failure is addressed according to the modified Marshall score
Secondary endpoints 8
- Individual components of the primary outcome
- Mortality (during follow-up): 14-day mortality or 28-day mortality or In hospital mortality
- New onset organ failure (during follow-up)
- Infectious complications (i.e. pneumonia, urinary tract, wound infections or infected (peri-) pancreatic necrosis)
- The need (and number of) for surgical, endoscopical or radiologic interventions
- CRP level on day 0, 1, 2, 3, 5 and 7
- Total length of hospital stay (days)
- Total length of ICU stay (days)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD2479933 · Product
- Active substance
- Glycerol
- Pharmaceutical form
- EMULSION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2 millilitre(s)/kilogram
- Max total dose
- 14 millilitre(s)/kilogram
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- B05BA02 — FAT EMULSIONS
- Marketing authorisation
- 443004
- MA holder
- FRESENIUS KABI DEUTSCHLAND GMBH
- MA country
- Estonia
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Stichting Radboud University Medical Center
- Sponsor organisation
- Stichting Radboud University Medical Center
- Address
- Geert Grooteplein Zuid 10
- City
- Nijmegen
- Postcode
- 6525 GA
- Country
- Netherlands
Scientific contact point
- Organisation
- Stichting Radboud University Medical Center
- Contact name
- Anne Nagelhout
Public contact point
- Organisation
- Stichting Radboud University Medical Center
- Contact name
- Anne Nagelhout
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Fresenius Kabi AG ORG-100002003
|
Bad Homburg, Germany | Other |
| The Danish GCP units ORL-000010299
|
Frederiksberg, Denmark | On site monitoring |
Locations
2 EU/EEA countries · 16 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 20 | 1 |
| Netherlands | Ongoing, recruiting | 212 | 15 |
| Rest of world | — | 0 | — |
Investigational sites
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
gastroenterology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Haga Hospital
gastroenterology, Els Borst-Eilersplein 275, 2545 AA, 's-Gravenhage
Bravis Ziekenhuis
gastroenterology, Boerhaavelaan 25, 4708 AE, Roosendaal
Radboud universitair medisch centrum
Surgery, Huispost 935, P. O. Box 9101, Nijmen
Catharina Ziekenhuis Stichting
gastroenterology, Michelangelolaan 2, 5623 EJ, Eindhoven
Medisch Spectrum Twente
gastroenterology, Koningsplein 1, 7512 KZ, Enschede
Sint Franciscus Vlietland Groep Stichting
Gastroenterology, Kleiweg 500, 3045 PM, Rotterdam
Ziekenhuis Gelderse Vallei Stichting
gastroenterology, Willy Brandtlaan 10, 6716 RP, Ede Gld
Amsterdam UMC
gastroenterology, De Boelelaan 1117, 1081 HV, Amsterdam
Canisius Wilhelmina Hospital
gastroenterology, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
Jeroen Bosch Ziekenhuis
gastroenterology, Henri Dunantstraat 1, 5223 GZ, 's-Hertogenbosch
Academisch Ziekenhuis Leiden
gastroenterology, Einthovenweg 20, 2333 ZC, Leiden
Rijnstate Ziekenhuis Stichting
Gastroenterology, Wagnerlaan 55, 6815 AD, Arnhem
Universiteit Maastricht
gastroenterology, P Debyelaan 25, 6229 HX, Maastricht
Meander Medisch Centrum
gastroenterology, Maatweg 3, 3813 TZ, Amersfoort
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2024-11-18 | 2025-11-13 | |||
| Netherlands | 2022-05-09 | 2022-07-15 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-68296
- Sponsor became aware
- 2024-01-27
- Date of breach
- 2024-01-27
- Submission date
- 2025-01-29
- Member states concerned
- Netherlands, Denmark
- Categories
- Protocol
- Areas impacted
- Subject safety
- Benefit-risk balance changed
- No
- Description
- Background:
A patient originally included in the intervention arm of the study did not meet the criterion for predicted severe acute pancreatitis (AP) on reflection. This was due to a misunderstanding around the CRP cut-off value.
Description of the situation:
- At the time of reporting, there was an assumption among the reporting physician assistants that the cut-off value for predicted severe acute pancreatitis was a CRP > 100.
- At the time of assessment by the physician-investigator, it was explicitly asked whether there was a predicted severe acute pancreatitis. This was answered ‘yes’, based on the assumption that a CRP of 130 met the (misunderstood) cut-off value.
- It was also asked whether the CRP was higher than 150 (the actual cut-off value according to the protocol). Unfortunately, again, 100 was understood as the cut-off value, resulting in the patient being wrongly included.
After draw:
- After draw, the patient's CRP was found to be 130, meaning she had predicted mild pancreatitis and did not meet the criterion for predicted severe acute pancreatitis.
- This was confirmed by low values in the APACHE and IMRIE scores.
Follow-up actions:
- Laboratory applications had already been made, but fish oil had not yet been started.
- Immediately after the study team became aware of the error, all further requests were cancelled.
- No further study action was taken by the patient.
Conclusion:
The patient did not meet the inclusion criterion for predicted severe acute pancreatitis due to a misunderstanding of the CRP cut-off value. Although the patient was initially randomised, she did not receive study medication and all further study procedures were immediately discontinued upon discovery of the error. - Sponsor actions
- Explanation for Late Notification of Protocol Violation
Following the identification of a protocol violation, the inclusion criteria were thoroughly reviewed and clarified with the assistant physician involved. Additionally, the inclusion criteria have been clearly outlined on the study website (www.pancreatitis.nl) to ensure accessibility. To prevent future occurrences, we have implemented stricter procedures during screening: all criteria are now systematically verified during calls, and laboratory results and controls are reviewed and shared to calculate the predicted severity of the condition.
The delay in reporting this violation occurred because we initially did not classify it as such. The patient did not receive any study medication and therefore was not exposed to unnecessary risk. Furthermore, the laboratory values collected for the study aligned with the patient’s routine laboratory assessments, with the study merely requiring the addition of some extra parameters. As a result, we determined that there was no immediate safety concern for the patient.
However, upon further discussion, we concluded that the incident did constitute an erroneous randomisation and therefore warranted classification as a protocol violation. Recognizing this, we have formally reported the violation, albeit later than expected. We hope that the measures we have taken to reinforce protocol adherence and our transparent reporting demonstrate our commitment to the integrity of the trial and patient safety.
We apologize for the delay in notification and assure you that steps have been taken to prevent similar delays in the future.
| Organisation | City | Country | Type |
|---|---|---|---|
| Universiteit Maastricht | Maastricht | Netherlands | Clinical facility BE/BA |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 26 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol EU CT number 2023-505220-57-03 | 17 |
| Protocol (for publication) | D1_Summary of Changes Protocol EU CT 2023-505220-57-03_SM-05_RFI-I | 1 |
| Protocol (for publication) | D4_ iPCQ Danish version | 1 |
| Protocol (for publication) | D4_Combined questionnaires | 1 |
| Protocol (for publication) | D4_Effective_Netherland EQ-5D-5L Paper Self-Complete | 1 |
| Protocol (for publication) | D4_EQ-5D-5L Danish version | 1 |
| Protocol (for publication) | D4_NL iMCQ vragenlijst | 1 |
| Protocol (for publication) | D4_NL iPCQ vragenlijst 2018 | 1 |
| Protocol (for publication) | D4_SF 36 Danish version | 1 |
| Protocol (for publication) | D4_SF 36 RAND-36-meetinstr | 1 |
| Recruitment arrangements (for publication) | Blank document | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment procedure | 3 |
| Recruitment arrangements (for publication) | K1_Recruitment procedure | 1 |
| Subject information and informed consent form (for publication) | L1_IFC PLANCTON trial patient | 2 |
| Subject information and informed consent form (for publication) | L1_Leaflet Dine rettigheder som forsgsperson i forsg med medicin | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PLANCTON trial legal representative | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PLANCTON trial legal representative with track changes | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PLANCTON Trial patient | 8 |
| Subject information and informed consent form (for publication) | L1_SIS PLANCTON trial patient | 3 |
| Subject information and informed consent form (for publication) | L2_Subject information material text information video | 1 |
| Subject information and informed consent form (for publication) | S13_Appendiks Genomforskning - srligt tillg om retten til ikke viden | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Omegaven Dutch | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Omegaven English | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_DM EU CT 2023-505220-57-03 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_ENG EU CT 2023-505220-57-03 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NL EU CT 2023-505220-57-03 | 1 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-10-12 | Netherlands | Acceptable 2023-11-08
|
2023-11-08 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-01-15 | Netherlands | Acceptable 2024-04-10
|
2024-04-10 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-06-25 | Netherlands | Acceptable | 2024-08-07 |
| 4 | SUBSEQUENT ADDITION OF MSC | APP-4 | 2024-08-28 | 2024-11-18 | ||
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-11-20 | Netherlands | Acceptable 2025-02-24
|
2025-02-24 |
| 6 | SUBSTANTIAL MODIFICATION | SM-6 | 2026-01-29 | Netherlands | Acceptable 2026-04-01
|
2026-04-01 |