Lactated Ringer's Versus Normal Saline for Acute Pancreatitis

NCT ID: NCT03642769

Last Updated: 2021-12-08

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

NA

Total Enrollment

121 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-18

Study Completion Date

2021-08-16

Brief Summary

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Acute pancreatitis is a common problem in the United States necessitating 275,000 hospital admissions per year, with resultant healthcare costs of approximately 2.5 billion USD annually. As numerous trials have failed to show a benefit to specific pharmacologic therapies in acute pancreatitis, the mainstay of treatment has been both supportive care and early, aggressive fluid resuscitation. Small randomized studies have shown conflicting results with regards to the influence of resuscitation fluid on outcomes in acute pancreatitis, necessitating a large randomized trial to clarify if fluid choice matters or not in the treatment of acute pancreatitis.

The objective of this study is to assess the comparative efficacy of normal saline versus lactated ringer's solution in the management of acute pancreatitis.

Patients presenting to the Los Angeles County Hospital with acute pancreatitis will be randomized to fluid resuscitation with NS or LR with volumes of fluid administered according to a pre-determined algorithm that will be the same for both treatment arms.

The primary outcome of the study will be the change in SIRS prevalence from enrollment to 24 hours. Secondary outcomes will include the change in SIRS prevalence from enrollment to 48 hours and 72 hours, development of moderately severe or severe pancreatitis, change in PASS score, ICU admission, length of hospitalization, persistent pain or disability after discharge, and time of advancement to oral diet and discharge.

Detailed Description

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Background: Acute pancreatitis is a common problem in the United States necessitating 275,000 hospital admissions per year, with resultant healthcare costs of approximately 2.5 billion USD annually. As numerous trials have failed to show a benefit to specific pharmacologic therapies in acute pancreatitis, the mainstay of treatment has been both supportive care and early, aggressive fluid resuscitation. Small randomized studies have shown conflicting results with regards to the influence of resuscitation fluid on outcomes in acute pancreatitis, necessitating a large randomized trial to clarify if fluid choice matters or not in the treatment of acute pancreatitis.

Objective: To assess the comparative efficacy of normal saline versus lactated ringer's solution in the management of acute pancreatitis.

Study Design: Patients presenting to the Los Angeles County Hospital with acute pancreatitis are the focus population of this study. Patients will be randomized to fluid resuscitation with NS or LR within 8 hours of diagnosis of pancreatitis. The inclusion and exclusion criterion will be assessed (see below). Randomization will be performed using a random sequence algorithm with concealed allocation. The patients will be blinded to allocation by covering the bag with an opaque covering. A study physician determining the outcomes will also be blinded. Following randomization, the volumes of fluid administered for the resuscitation will be determined by a pre-determined algorithm that will be the same for both treatment arms. The hydration algorithm is as follows: all patients will receive a bolus of the treatment fluid at a rate of 5 mL/kg/hour to be administered over the first two hours (total 10 mL/kg) with an assessment for volume overload at 1 hour. They will then will receive maintenance fluids at a rate of 3 mL/kg/hour. After 12 hours participants will have blood urea nitrogen (BUN) assessed, which is part of the standard clinical procedure. Those who do not have a fall in this parameter or who develop SIRS by this 12 hour checkpoint will receive a second 5 mL/kg/hour bolus over two hours (as above) of their designated treatment fluid followed by further treatment fluid at a rate of 3 mL/kg/hour. Those who do have a fall in BUN will receive further treatment fluid at a rate of 3 mL/kg/hour for 12 additional hours. Patients' volume status will be assessed in the following manner: study physicians will perform a targeted physical exam which will include assessment of JVD, lung auscultation, and monitoring for edema Q12 hours for the first 24 hours, then daily for the remainder of the hospital admission. In elderly patients and those with co-morbidities, the targeted physical exam will be performed Q12 hours for the entire hospital admission. Vitals will also be obtained Q6-8 hours. If they develop signs of fluid overload including pitting edema, ascites, anasacra, pulmonary edema, or dyspnea, or signs of renal failure including oliguria, anuria, or hypotension, they will have their fluid rate managed at the discretion of their treating physicians. However, it will be requested that if further fluid is given that it be the assigned type (LR versus NS). At 24 hours patients will be assessed for SIRS development (see outcomes). Beyond this point fluid rate will be per the primary team though it still be encouraged that the assigned type of fluid (LR versus NS) is used for additional resuscitation with the rate and volume beyond this point at the discretion of the treating physician. However, if the treating physicians have a strong preference to change to a different fluid type for clinical reasons this will be recorded (for post hoc analysis) and the patient included in the intention to treat analysis.

Conditions

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Pancreatitis, Acute

Keywords

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Pancreatitis Fluids SIRS Management Lactated Ringer Normal Saline

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Lactated Ringer

Patients will receive fluid administration of Lactated Ringer's solution at a pre-determined volume algorithm that is the same for both arms

Group Type ACTIVE_COMPARATOR

Fluid administration

Intervention Type OTHER

Fluid administration of bolus and maintenance fluids

Normal Saline

Patients will receive fluid administration of Normal Saline solution at a pre-determined volume algorithm that is the same for both arms

Group Type EXPERIMENTAL

Fluid administration

Intervention Type OTHER

Fluid administration of bolus and maintenance fluids

Interventions

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Fluid administration

Fluid administration of bolus and maintenance fluids

Intervention Type OTHER

Other Intervention Names

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Fluid

Eligibility Criteria

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Inclusion Criteria

* Presentation with acute pancreatitis as defined by two of three criterion; amylase or lipase \> 3x the upper limit of normal, classical abdominal pain, or imaging suggestive of pancreatitis. Such radiographic findings include swelling, edema, or heterogeneity of the gland or peripancreatic fluid or stranding.

Exclusion Criteria

* Patients with severe pancreatitis as defined by the Revised Atlanta Classification will be excluded. Severe pancreatitis is defined by the Revised Atlanta Classification as those with a Modified Marshall score of \>2 for their cardiovascular renal, or respiratory system will be excluded (Figure 2).13 Practically this includes patients with systolic blood pressure \<90, serum creatinine \>1.9, and PaO2/FiO2 \<300 (Figure 3). Since blood gases are unlikely to be drawn on those with mild pancreatitis we will exclude patients with an oxygen saturation \<92% on room air and certainly any patients which require intubation for respiratory failure due to pancreatitis.
* Patients who cannot tolerate increased doses of fluids for other reasons will also be excluded. This consists of those with cardiac insufficiency (CI, \>NYHA Class II heart failure), pulmonary edema, dialysis requirement, or severe liver dysfunction (albumin \< 3mg/dL, known cirrhosis).
* Pregnant women will also be excluded as they are prone to retain sodium and water, which puts them at increased risk of pulmonary congestion, ascites or peripheral edema.
* Patients who are incarcerated, younger than eighteen, or unable to give informed consent will be excluded.
* Individuals who present with clinical signs of edema or anasacra, including pulmonary congestion, peripheral swelling, and ascites, will also be ineligible for the study.
* Administration of fluids prior to the enrollment in the study will not be an exclusion criterion as this reflects actual clinical practice (hydration during evaluation period) however all fluids given prior to the study will be meticulously recorded.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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James Buxbaum

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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James Buxbaum, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

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LAC+USC Medical Center

Los Angeles, California, United States

Site Status

Countries

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United States

References

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Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, Smith B, Banks PA, Conwell DL. Lactated Ringer's solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011 Aug;9(8):710-717.e1. doi: 10.1016/j.cgh.2011.04.026. Epub 2011 May 12.

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Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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APP-17-06494

Identifier Type: -

Identifier Source: org_study_id