NCT05781243

Brief Summary

Background: Some evidence suggests that fluid resuscitation with lactated Ringer's solution (LR) may have an anti-inflammatory effect on acute pancreatitis (AP) when compared to normal saline (NS), and may be associated with a decrease in severity, but existing single center randomized controlled trials showed conflicting results. The WATERLAND trial aims to investigate the efficacy and safety of fluid resuscitation using LR compared to NS in patients with AP. Methods: The WATERLAND trial is an international multicenter, open-label, parallel-group, randomized, controlled, superiority trial. Patients will be randomly assigned in a 1:1 ratio to receive LR versus NS-based fluid resuscitation for at least 48 hours. The primary outcome will be moderately severe or severe AP, according to the revision of the Atlanta classification. The secondary objectives of the WATERLAND trial are to determine the effect of LR versus NS fluid resuscitation on several efficacy and safety outcomes in patients with AP. A total sample of 720 patients, 360 in the LR group and 360 in the NS group, will achieve 90% power to detect a difference between the group proportions of 10%, assuming that the frequency of moderately severe or severe AP in the LR group will be 17%. A loss to follow-up of 10% of patients is expected, so the total sample size will be 396 patients in each treatment arm (792 patients overall). The test statistic used is the two-sided Z test with pooled variance set at a 0.05 significance level. Discussion: The WATERLAND study aims to improve the early management of AP. Fluid resuscitation is an inexpensive treatment available in any hospital center worldwide. If a better evolution of pancreatitis is demonstrated in one of the treatment arms, it would have important repercussions in the management of this frequent disease.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
792

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jun 2023

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 25, 2023

Completed
26 days until next milestone

First Posted

Study publicly available on registry

March 23, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

June 19, 2023

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2024

Completed
Last Updated

January 20, 2025

Status Verified

January 1, 2025

Enrollment Period

1.3 years

First QC Date

February 25, 2023

Last Update Submit

January 16, 2025

Conditions

Acute Pancreatitis

Keywords

Normal salineLactated Ringer solutionAcute pancreatitisFluid TherapyFluid resuscitation

Outcome Measures

Primary Outcomes (1)

  • Number of Participants with moderately severe or severe acute pancreatitis

    Presence of local complications, exacerbation of previous comorbidity or organ failure, according to the definitions of these complications provided by the revised Atlanta Classification (https://doi.org/10.1136/gutjnl-2012-302779)

    From date of randomization until 30 days after randomization

Secondary Outcomes (28)

  • Number of participants with local complications

    From date of randomization until 30 days after randomization

  • Number of participants with necrotizing pancreatitis

    From date of randomization until 30 days after randomization

  • Number of participants with infection of pancreatic collections or necrosis

    From date of randomization until 30 days after randomization

  • Number of participants with systemic inflammatory response syndrome

    At 24 and 48 hours

  • Number of systemic inflammatory response syndrome criteria

    At 24 and 48 hours

  • +23 more secondary outcomes

Study Arms (2)

Lactated Ringer solution (LR)

EXPERIMENTAL

LR: Lactated Ringer solution. Patients in the LR treatment arm will receive fluid therapy based on lactated Ringer's solution for a minimum of 48 hours.

Drug: Lactated Ringer Solution

Normal saline (NS)

ACTIVE COMPARATOR

NS: Normal Saline. Patients in the NS treatment arm will receive fluid therapy based on normal saline for a minimum of 48 hours.

Drug: Normal saline

Interventions

Lactated Ringer SolutionDRUG

Patients in the LR (Lactated Ringer solution) treatment arm will receive fluid therapy based on lactated Ringer's solution for a minimum of 48 hours.

Lactated Ringer solution (LR)
Normal salineDRUG

Patients in the NS (Normal Saline) treatment arm will receive fluid therapy based on lactated Ringer's solution for a minimum of 48 hours.

Normal saline (NS)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient is 18 years or older
  • Diagnosis of acute pancreatitis according to the revision of the Atlanta classification (Banks et al, Gut 2013), which requires at least two of the following three criteria: A) typical abdominal pain, B) increase in serum amylase or lipase levels higher than three times the upper limit of normality, and C) signs of acute pancreatitis in imaging
  • Signature of informed consent

You may not qualify if:

  • New York Heart Association class II heart failure (slight limitation of physical activity; fatigue, palpitations, or dyspnea with ordinal physical activity) or worse, or ejection fraction \<50% in the last echocardiography
  • Decompensated cirrhosis (Child's class B or C)
  • Hyper or hyponatremia (\<135 or \>145 mEq/L)
  • Hyperkalemia (\>5 mEq/L)
  • Hypercalcemia (albumin or protein-corrected calcium \>10.5 mg/dL or 2.62 mmol/L)
  • Criteria for moderately severe or severe acute pancreatitis (revision of the Atlanta classification, Banks et al, Gut 2013) at recruitment: any of the following: A) presence of creatinine ≥1.9 mg/dL or ≥170 mmol/l, B) PaO2/FiO2≤300, C) systolic blood pressure \<90 mmHg despite initial fluid resuscitation, D) presence of local complications (acute peripancreatic fluid collections, acute necrotic collection, pseudocyst, walled-off necrosis, gastric outlet dysfunction, splenic or portal vein thrombosis, or colonic necrosis), E) exacerbation of previous comorbidity such as coronary artery disease or chronic lung disease, precipitated by the acute pancreatitis
  • Signs of volume overload or heart failure at recruitment (peripheral edema, pulmonary rales, or increased jugular ingurgitation at 45º)
  • Time from pain onset to arrival to emergency room \>24 h
  • Time from confirmation of pancreatitis to randomization \>8 h
  • Chronic pancreatitis defined by a Wirsung duct ≥4mm and/or pancreatic calcifications
  • More than 1 previous episode of acute pancreatitis (only 2 episodes of acute pancreatitis are allowed, one of them the present episode)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dr. Balmis General University Hospital

Alicante, 03010, Spain

Location

Related Publications (4)

  • Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.

    PMID: 23100216BACKGROUND

  • de-Madaria E, Buxbaum JL, Maisonneuve P, Garcia Garcia de Paredes A, Zapater P, Guilabert L, Vaillo-Rocamora A, Rodriguez-Gandia MA, Donate-Ortega J, Lozada-Hernandez EE, Collazo Moreno AJR, Lira-Aguilar A, Llovet LP, Mehta R, Tandel R, Navarro P, Sanchez-Pardo AM, Sanchez-Marin C, Cobreros M, Fernandez-Cabrera I, Casals-Seoane F, Casas Deza D, Lauret-Brana E, Marti-Marques E, Camacho-Montano LM, Ubieto V, Ganuza M, Bolado F; ERICA Consortium. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med. 2022 Sep 15;387(11):989-1000. doi: 10.1056/NEJMoa2202884.

    PMID: 36103415BACKGROUND

  • de-Madaria E, Sanchez-Marin C, Carrillo I, Vege SS, Chooklin S, Bilyak A, Mejuto R, Mauriz V, Hegyi P, Marta K, Kamal A, Lauret-Brana E, Barbu ST, Nunes V, Ruiz-Rebollo ML, Garcia-Rayado G, Lozada-Hernandez EE, Pereira J, Negoi I, Espina S, Hollenbach M, Litvin A, Bolado-Concejo F, Vargas RD, Pascual-Moreno I, Singh VK, Mira JJ. Design and validation of a patient-reported outcome measure scale in acute pancreatitis: the PAN-PROMISE study. Gut. 2021 Jan;70(1):139-147. doi: 10.1136/gutjnl-2020-320729. Epub 2020 Apr 3.

    PMID: 32245906BACKGROUND

  • Guilabert L, Cardenas-Jaen K, Vaillo-Rocamora A, Garcia Garcia de Paredes A, Chhoda A, Sheth SG, Lopez-Valero C, Zapater P, Navarrete-Munoz EM, Maisonneuve P, Hernandez-Barco YG, Capurso G, Buxbaum JL, de-Madaria E; ERICA consortium. Normal saline versus lactated Ringer's solution for acute pancreatitis resuscitation, an open-label multicenter randomized controlled trial: the WATERLAND trial study protocol. Trials. 2024 Oct 21;25(1):699. doi: 10.1186/s13063-024-08539-2.

    PMID: 39434191BACKGROUND

Related Links

MeSH Terms

Conditions

Pancreatitis

Interventions

Ringer's LactateSaline Solution

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Enrique de-Madaria, MD PhD

    Dr. Balmis General University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator of clinical pancreatology research group-ERICA consortium, ISABIAL

Study Record Dates

First Submitted

February 25, 2023

First Posted

March 23, 2023

Study Start

June 19, 2023

Primary Completion

September 30, 2024

Study Completion

September 30, 2024

Last Updated

January 20, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will share

Members of the ERICA consortium that recruited patients in the WATERLAND trial may claim access to the final dataset to perform post-hoc studies; these proposals will be studied by the steering committee.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
Data will be available upon publication of the main study.
Access Criteria
1. Have enrolled patients in the WATERLAND study. 2. The Steering Committee will evaluate the project and decide whether it is of sufficient scientific quality.

Locations

ES(1)