FLUYT-prevent trial

ISRCTN	ISRCTN13659155
DOI	https://doi.org/10.1186/ISRCTN13659155
Clinical Trials Information System (CTIS)	2015-000829-37
Protocol serial number	Version 2 (dated 09/03/2015)
Sponsor	Radboud University Medical Center
Funders	Radboud University Medical Center, Department of Gastroenterology and Hepatology, Netherlands Organisation for Health Research and Development

Submission date: 04/03/2015
Registration date: 18/05/2015
Last edited: 22/03/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Every year 17,000 endoscopic retrograde cholangiopancreatographies (ERCP) are performed in the Netherlands. ERCP is a procedure to evaluate and treat conditions concerning the bile duct. The most common complication is post-ERCP pancreatitis (PEP), occurring in 3%-16% of patients undergoing the procedure. PEP leads to prolonged hospitalization with substantial economic impact. Rectal anti-inflammatory drugs carry the most solid evidence in decreasing the PEP rate and this is the current standard of care according to the European Society of Gastrointestinal Endoscopy guideline. A new strategy to prevent PEP was tested in a study which compared standard intravenous (IV) fluid administration with an aggressive rehydration protocol with Ringer’s lactate (RL, a type of infusion fluid). However, the limitations of the study were the small number of patients involved and the fact that none of them received anti-inflammatory drugs. The aim of this study is to investigate the value of peri-ERCP hydration with RL on top of standard care, including anti-inflammatory drugs.

Who can participate?
Patients between 18 and 85 years of age undergoing ERCP with a moderate-severe risk for developing PEP

What does the study involve?
Participants are randomly allocated to one of two groups. One group receives intensive RL hydration in addition to rectal anti-inflammatory drugs. The other group receives no or mild hydration with normal saline (salt water) in addition to rectal anti-inflammatory drugs (the standard of care). Participants have the following tests: blood sampling, body measurements and a questionnaire (15-30 min) at 30, 90 and 180 days after the procedure.

What are the possible benefits and risks of participating?
Possible risks are associated with overhydration (i.e. pulmonary edema, ankle edema). However, considering the total volume of fluids used and the exclusion of patients prone to this complication, the risk should be very low. It must be stressed that there is no standard infusion rate, volume and type of fluid, in the peri-ERCP setting. The two regimens proposed in this study are within the range daily common practice use.

Where is the study run from?
A number of hospitals in the Netherlands

When is the study starting and how long is it expected to run for?
April 2015 to November 2016

Who is funding the study?
1. Radboud University Medical Center
2. Netherlands Organisation for Health Research and Development

Who is the main contact?
Dr Erwin van Geenen
erwin.vangeenen@radboudumc.nl

Contact information

Dr Erwin van Geenen
Scientific

Radboud University Medical Center
Geert Grooteplein Zuid 10
Nijmegen
6525 GA
Netherlands

Phone	(024) 361 47 60
Email	erwin.vangeenen@radboudumc.nl

Study information

Primary study design	Interventional
Study design	Multicenter randomized superiority trial
Secondary study design	Randomised parallel trial
Study type	Participant information sheet
Scientific title	Fluid hydration to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis
Study acronym	FLUYT-prevent
Study objectives	Peri-procedural intensive lactated Ringer's solution hydration on top of rectal non-steroid anti-inflammatory drugs will reduce the incidence of post-ERCP pancreatitis (PEP) in a moderate-to-high risk population, and may even reduce the percentage of severe PEP.
Ethics approval(s)	On the 14/04/2015, the Medical research Ethics Committees United (MEC-U) gave a positive verdict for the trial. Also, as a Competent Authority for the review of clinical trials in the Netherlands, the CCMO has performed a marginal assessment of the clinical trial. The Competent Authority found no objection against execution of the trial within the Netherlands. This verdict was given on 06/05/2015.
Health condition(s) or problem(s) studied	Choledocholithiasis and other conditions requiring endoscopic retrograde cholangiopancreatography (ERCP)
Intervention	High volume intravenous hydration with lactated Ringer's solution Added 17/02/2017: Partcipants are randomised to one of two treatment arms: 1. Control group: 100mg rectal NSAID + no or mild hydration with normal saline (max 1.5mL/kg/hr, max. 3L/24h) 2. Intervention group: 100mg rectal NSAID + hydration with lactated Ringer’s solution (20mL/kg <60min, starting at the beginning of ERCP (scope-mouth contact), followed by 3mL/kg/hr for 8 hours) Patients are discharged after ERCP after a minimal clinical stay of 24 hours. It is at the discretion of the treating physician whether an admission or longer monitoring is indicated. All patients are followed up for 180 days after randomization.
Intervention type	Mixed
Primary outcome measure(s)	Post-ERCP pancreatitis, according to Cotton criteria
Key secondary outcome measure(s)	1. Severity of post-ERCP pancreatitis measured at discharge (Cotton criteria) 2. Severe morbidity (Atlanta criteria) or death measured at discharge 3. ERCP related complications within 48 hours after ERCP 4. Fluid hydration related complications within 24 hours after ERCP or at the latest at discharge 5. Length of hospital stay (including stay on the intensive care unit) measured after a follow up period of 6 months (so readmissions can be taken into account) 6. Direct and indirect costs measured after 6 months of follow up 7. Risk factors for developing post-ERCP pancreatitis measured at baseline 8. Generic health-related quality of life measured with EQ5D and SF36 9. Exocrine and endocrine pancreatic insufficiency at 180 days: fecal elastase-1 and HbA1c 10. Incidence of delayed post-ERCP pancreatitis
Completion date	03/12/2019

Eligibility

Participant type(s)	Patient
Age group	Mixed
Sex	All
Target sample size at registration	826
Total final enrolment	826
Key inclusion criteria	1. Requiring ERCP 2. Between 18 and 85 years of age 3. Signed informed consent
Key exclusion criteria	1. Allergy to NSAIDs or other contraindications 2. Ongoing acute pancreatitis 3. Ongoing hypotension, including those with sepsis 4. Cardiac insufficiency (CI, >NYHA Class I heart failure) 5. Renal insufficiency (RI, creatinin clearance <40ml/min) 6. Active ulcer disease 7. Severe liver dysfunction: liver cirrhosis and ascites 8. Respiratory insufficiency (pO2<60mmHg or 90% despite FiO2 of 30% or requiring mechanical ventilation) 9. Pregnancy 10. Hyponatremia (Na+ levels < 130mmol/l) 11. Hypernatremia (Na+ levels > 150mmol/l) 12. Oedema 13. Low risk of PEP: chronic calcific pancreatitis (PD intervention is allowed) or pancreatic head mass or routine biliary stent exchange or re-ERCP with a history of endoscopicsphincterotomy with a CBD intervention (PD intervention is allowed)
Date of first enrolment	05/06/2015
Date of final enrolment	01/08/2019

Locations

Countries of recruitment

Netherlands

Study participating centres

Radboud University Medical Center

Nijmegen
-
Netherlands

St. Antonius Hospital

Nieuwegein
-
Netherlands

Antoni van Leeuwenhoek Hospital

Amsterdam
-
Netherlands

Jeroen Bosch Hospital

's Hertogenbosch
-
Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam
-
Netherlands

Erasmus Medical Center

Rotterdam
-
Netherlands

Isala Clinics

Zwolle
-
Netherlands

Spaarne Hospital

Haarlem
-
Netherlands

Medisch Spectrum Twente Hospital

Enschede
-
Netherlands

Univeristy Medical Center Utrecht

Utrecht
-
Netherlands

VU University Medical Center

Amsterdam
-
Netherlands

Albert Schweitzer Hospital

Dordrecht
-
Netherlands

Amphia Hospital

Breda
-
Netherlands

Canisius Wilhelmina Hospital

Nijmegen
-
Netherlands

Diakonessenhuis

Utrecht
-
Netherlands

Gelderse Vallei Hospital

Ede
-
Netherlands

HAGA hospital

Den Haag
-
Netherlands

Maasstad hospital

Rotterdam
-
Netherlands

Martini hospital

Groningen
-
Netherlands

Meander Medical Centre

Amersfoort
-
Netherlands

Rijnstate Hospital

Arnhem
-
Netherlands

Zuyderland Hospital

Heerlen
-
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Erwin van Geenen (Erwin.vangeenen@radboudumc.nl).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/05/2021	22/03/2021	Yes	No
Protocol article	protocol	02/04/2018		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

22/03/2021: Publication reference added.
19/01/2021: The intention to publish date was changed from 30/06/2020 to 01/06/2021.
17/09/2019: The following changes were made:
1. The overall trial end date was updated from 01/07/2019 to 03/12/2019.
2. The total final enrolment was added.
3. The intention to publish date was updated from 01/01/2020 to 30/06/2020.
4. The trial participating centres were updated.
08/02/2019: The recruitment end date was changed from 01/01/2019 to 01/08/2019
03/04/2018: Publication reference added.
10/02/2017: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/11/2016 to 01/01/2019.
2. The overall trial end date was changed from 01/01/2017 to 01/07/2019.