Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Dr Erwin van Geenen
ORCID ID
Contact details
Radboud University Medical Center
Geert Grooteplein Zuid 10
Nijmegen
6525 GA
Netherlands
(024) 361 47 60
erwin.vangeenen@radboudumc.nl
Additional identifiers
EudraCT number
2015-000829-37
ClinicalTrials.gov number
Protocol/serial number
Version 2 (dated 09/03/2015)
Study information
Scientific title
Fluid hydration to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis
Acronym
FLUYT-prevent
Study hypothesis
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
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.
Study design
Multicenter randomized superiority trial
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
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
Phase
Drug names
Primary outcome measure
Post-ERCP pancreatitis, according to Cotton criteria
Secondary outcome measures
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
Overall trial start date
01/04/2015
Overall trial end date
03/12/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Requiring ERCP
2. Between 18 and 85 years of age
3. Signed informed consent
Participant type
Patient
Age group
Mixed
Gender
Both
Target number of participants
826 patients
Total final enrolment
826
Participant 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)
Recruitment start date
05/06/2015
Recruitment end date
01/08/2019
Locations
Countries of recruitment
Netherlands
Trial participating centre
Radboud University Medical Center
Nijmegen
-
Netherlands
Trial participating centre
St. Antonius Hospital
Nieuwegein
-
Netherlands
Trial participating centre
Antoni van Leeuwenhoek Hospital
Amsterdam
-
Netherlands
Trial participating centre
Jeroen Bosch Hospital
's Hertogenbosch
-
Netherlands
Trial participating centre
Onze Lieve Vrouwe Gasthuis
Amsterdam
-
Netherlands
Trial participating centre
Erasmus Medical Center
Rotterdam
-
Netherlands
Trial participating centre
Isala Clinics
Zwolle
-
Netherlands
Trial participating centre
Spaarne Hospital
Haarlem
-
Netherlands
Trial participating centre
Medisch Spectrum Twente Hospital
Enschede
-
Netherlands
Trial participating centre
Univeristy Medical Center Utrecht
Utrecht
-
Netherlands
Trial participating centre
VU University Medical Center
Amsterdam
-
Netherlands
Trial participating centre
Albert Schweitzer Hospital
Dordrecht
-
Netherlands
Trial participating centre
Amphia Hospital
Breda
-
Netherlands
Trial participating centre
Canisius Wilhelmina Hospital
Nijmegen
-
Netherlands
Trial participating centre
Diakonessenhuis
Utrecht
-
Netherlands
Trial participating centre
Gelderse Vallei Hospital
Ede
-
Netherlands
Trial participating centre
HAGA hospital
Den Haag
-
Netherlands
Trial participating centre
Maasstad hospital
Rotterdam
-
Netherlands
Trial participating centre
Martini hospital
Groningen
-
Netherlands
Trial participating centre
Meander Medical Centre
Amersfoort
-
Netherlands
Trial participating centre
Rijnstate Hospital
Arnhem
-
Netherlands
Trial participating centre
Zuyderland Hospital
Heerlen
-
Netherlands
Sponsor information
Organisation
Radboud University Medical Center
Sponsor details
Geert Grooteplein Zuid 10
Nijmegen
6525 GA
Netherlands
(024) 361 47 60
erwin.vangeneen@radboudumc.nl
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Radboud University Medical Center, Department of Gastroenterology and Hepatology
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Netherlands Organisation for Health Research and Development
Alternative name(s)
Netherlands Organisation for Health Research and Development
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
Netherlands
Results and Publications
Publication and dissemination plan
A manuscript with the study results will be sent to a peer-reviewed journal for publication in Q4/2019-Q1/2020, regardless of the outcome. Around the same date, an abstract will be sent to international congresses such as the DDW and UEGW.
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).
Intention to publish date
30/06/2020
Participant level data
Available on request
Basic results (scientific)
Publication list
2018 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/29606135