Normal Saline Versus Lactated Ringer's Solution for Acute Pancreatitis Resuscitation

NCT ID: NCT05781243

Last Updated: 2025-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

792 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-19

Study Completion Date

2024-09-30

Brief Summary

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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.

Detailed Description

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The entire protocol is published in open-access format, including the Statistical Analysis plan, in the journal Trials: https://doi.org/10.1186/s13063-024-08539-2

Conditions

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Acute Pancreatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Lactated Ringer solution (LR)

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.

Group Type EXPERIMENTAL

Lactated Ringer Solution

Intervention Type DRUG

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.

Normal saline (NS)

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

Group Type ACTIVE_COMPARATOR

Normal saline

Intervention Type DRUG

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

Interventions

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Lactated Ringer Solution

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.

Intervention Type DRUG

Normal saline

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto de Salud Carlos III

OTHER_GOV

Sponsor Role collaborator

Universidad Miguel Hernandez de Elche

OTHER

Sponsor Role collaborator

Hospital del Mar

OTHER

Sponsor Role collaborator

Hospital Clinico Universitario de Santiago

OTHER

Sponsor Role collaborator

Hospital Clínico Universitario de Valencia

OTHER

Sponsor Role collaborator

Hospital Costa del Sol

OTHER

Sponsor Role collaborator

Corporacion Parc Tauli

OTHER

Sponsor Role collaborator

Hospital Clínico Universitario Lozano Blesa

OTHER

Sponsor Role collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role collaborator

Hospital Universitario La Fe

OTHER

Sponsor Role collaborator

Hospital Miguel Servet

OTHER

Sponsor Role collaborator

Hospital Universitario Ramon y Cajal

OTHER

Sponsor Role collaborator

Hospital Universitario Insular Gran Canaria

OTHER

Sponsor Role collaborator

University Hospital Virgen de las Nieves

OTHER

Sponsor Role collaborator

Hospital Universitario de Burgos

OTHER

Sponsor Role collaborator

Hospital Universitario Lucus Augusti

OTHER

Sponsor Role collaborator

Hospital Universitario Marqués de Valdecilla

OTHER

Sponsor Role collaborator

Hospital Universitario Puerta del Mar

OTHER

Sponsor Role collaborator

Instituto de Investigación Sanitaria Hospital Universitario de la Princesa

OTHER

Sponsor Role collaborator

Dr. Negrin University Hospital

OTHER

Sponsor Role collaborator

Hospital Regional de Alta Especialidad del Bajio

OTHER

Sponsor Role collaborator

Asian Institute Of Medical Sciences

OTHER

Sponsor Role collaborator

Hospital Dr. Jaime Mendoza Sucre Bolivia

UNKNOWN

Sponsor Role collaborator

Hayatabad Medical Complex

OTHER_GOV

Sponsor Role collaborator

University Hospital Olomouc

OTHER

Sponsor Role collaborator

SIDS Hospital & Research Centre Gujarat India

UNKNOWN

Sponsor Role collaborator

Sanatorio Allende

OTHER

Sponsor Role collaborator

University Hospital Bratislava

OTHER

Sponsor Role collaborator

University Hospital Sestre Milosrdnice

OTHER

Sponsor Role collaborator

Attikon Hospital

OTHER

Sponsor Role collaborator

Nuevo Hospital Iturraspe Santa Fe Argentina

UNKNOWN

Sponsor Role collaborator

Hospital Nacional Rosales

OTHER

Sponsor Role collaborator

Zagazig University

OTHER_GOV

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

Hospitales Universitarios Virgen del Rocío

OTHER

Sponsor Role collaborator

University Hospital of Girona Dr. Josep Trueta

NETWORK

Sponsor Role collaborator

Hospital of Navarra

OTHER

Sponsor Role collaborator

Hospital Clínico Universitario de Valladolid

OTHER

Sponsor Role collaborator

Hospital Universitario Central de Asturias

OTHER

Sponsor Role collaborator

Kalinga Hospital, Bhubaneswar

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role collaborator

Zhengzhou University

OTHER

Sponsor Role collaborator

Jinling Hospital, China

OTHER

Sponsor Role collaborator

Hospital Privado de Cordoba, Argentina

OTHER

Sponsor Role collaborator

Prince of Wales Hospital, Shatin, Hong Kong

OTHER

Sponsor Role collaborator

Postgraduate Institute of Medical Education and Research in Chandigarh

OTHER

Sponsor Role collaborator

RML Specialty Hospital

OTHER

Sponsor Role collaborator

Wannan Medical College Yijishan Hospital

OTHER

Sponsor Role collaborator

Bucharest Emergency Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital of Henan University of Science and Technology

OTHER

Sponsor Role collaborator

Emergency County Hospital Pius Brinzeu; Timisoara, Romania

NETWORK

Sponsor Role collaborator

King Hamad University Hospital, Bahrain

OTHER

Sponsor Role collaborator

Enrique de-Madaria

OTHER

Sponsor Role lead

Responsible Party

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Enrique de-Madaria

Principal Investigator of clinical pancreatology research group-ERICA consortium, ISABIAL

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Enrique de-Madaria, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Dr. Balmis General University Hospital

Locations

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Dr. Balmis General University Hospital

Alicante, , Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 23100216 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36103415 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32245906 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 39434191 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://pmc.ncbi.nlm.nih.gov/articles/PMC11492666/

Published study protocol and statistical analysis plan

Other Identifiers

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Eudract 2023-000010-18

Identifier Type: -

Identifier Source: org_study_id

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