Comparative Efficacy and Safety of Sodium Chloride Versus Lactated Ringer's Solution in Acute Pancreatitis Resuscitation: A Multicenter Randomized Controlled Trial
- Trial ID
- 2023-509879-16-00
- Protocol
- WATERLAND
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this trial is to evaluate the effect of **lactated Ringer solution** compared to normal saline on the severity and safety of **acute pancreatitis**. The clinical relevance of this objective lies in its potential to inform treatment protocols for acute pancreatitis, a condition characterized by inflammation of the pancreas that can lead to severe complications. The main efficacy endpoint is the frequency of moderately severe to severe acute pancreatitis, assessed according to the revision of the Atlanta classification. The main safety endpoint is a composite variable, including fluid overload, acute kidney injury, hyperkalemia, hypercalcemia, or acidosis.
Secondary objectives include investigating the effect of lactated Ringer solution compared to normal saline on secondary efficacy and safety endpoints. These secondary endpoints will provide additional insights into the broader impact of the treatment options on patient outcomes.
Participants
The clinical trial focuses on individuals diagnosed with **acute pancreatitis**. The study population includes both male and female participants aged 18 years and older. Participants are required to have a diagnosis of acute pancreatitis according to the revision of the Atlanta classification, which necessitates at least two of the following criteria: typical abdominal pain, elevated serum amylase or lipase levels exceeding three times the upper limit of normal, or imaging signs indicative of acute pancreatitis. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must provide informed consent to be included in the study. No specific lifestyle considerations such as diet or physical activity are highlighted for this trial.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **lactated Ringer's solution** compared to normal saline in the management of **acute pancreatitis**. This study is structured as an open-label, multicenter, randomized controlled trial. The trial aims to assess the impact of these solutions on the severity of acute pancreatitis, with the primary efficacy endpoint being the frequency of moderately severe to severe cases as per the revised Atlanta classification. The primary safety endpoint is a composite measure including fluid overload, acute kidney injury, hyperkalemia, hypercalcemia, or acidosis. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on June 19, 2023.
Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age (18 years or older) and a diagnosis of acute pancreatitis. This diagnosis requires at least two of the following: typical abdominal pain, elevated serum amylase or lipase levels, or imaging evidence of acute pancreatitis. Informed consent is also required. Follow-up visits will monitor the participants' response to treatment, with assessments of local complications, organ failure, and other secondary endpoints. The end-of-study visit will finalize data collection and assess the overall outcomes of the intervention.
The expected duration of participant involvement is up to 30 days post-randomization, during which the primary outcome will be evaluated. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or withdrawal of consent. The trial is categorized as a low-intervention study, reflecting its design and the nature of the interventions being tested. The study employs intravenous administration of the solutions, with a maximum daily dose of 36 milliliters per kilogram and a total maximum dose of 252 milliliters per kilogram over the treatment period. The trial is conducted in accordance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants.
Treatment
The clinical trial involves the administration of two distinct **solutions for infusion** to evaluate their effects on the severity and safety of acute pancreatitis. The first experimental medication is **Salina Fisiológica Grifols 0.9%**, a solution for infusion containing **sodium chloride** as the active substance. This solution is administered via **intravenous administration**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 36 milliliters per kilogram and a total maximum dose of 252 milliliters per kilogram over a treatment period of one day. The solution is manufactured by **Laboratorios Grifols, S.A.** in Spain and is classified under the ATC code B05BB01, indicating its use as an electrolyte solution.
The comparator treatment in the trial is **Freeflex Ringer Lactato**, another solution for infusion. This solution contains a combination of active substances: **sodium lactate solution, potassium chloride, sodium chloride, and calcium chloride dihydrate**. It is also administered via **intravenous infusion**. The dosing regimen mirrors that of the Salina Fisiológica Grifols, with a maximum daily dose of 36 milliliters per kilogram and a total maximum dose of 252 milliliters per kilogram, administered over a single day. This solution is produced by **Fresenius Kabi España S.A.U.** and shares the same ATC classification as the sodium chloride solution, B05BB01, denoting its role as an electrolyte solution. Both solutions are not formulated for pediatric use and are not classified as orphan drugs.
Efficacy
The efficacy of the clinical trial titled "Normal saline versus lactated Ringer’s solution for acute pancreatitis resuscitation, an open-label multicenter randomized controlled trial: the WATERLAND trial" will be assessed by evaluating the primary and secondary endpoints. The primary efficacy endpoint is the frequency of moderately severe to severe **acute pancreatitis** within the first 30 days after randomization, as defined by the revision of the Atlanta classification. This classification provides a standardized method for assessing the severity of acute pancreatitis, which is crucial for determining the efficacy of the treatment interventions being compared.
Secondary endpoints include a range of clinical outcomes such as local complications, necrotizing pancreatitis, systemic inflammatory response syndrome (SIRS), the number of SIRS criteria, PAN-PROMISE symptom scale, time to oral refeeding, invasive treatment, nutritional support, intensive care unit admission, exacerbation of coexisting conditions, any organ failure, persistent organ failure, shock, respiratory failure, kidney failure, death, hospital stay, and C-reactive protein levels. These endpoints will provide a comprehensive assessment of the treatment's impact on patient health and recovery.
Inclusion and Exclusion Criteria
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)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 19 Jun 2023 | — |
 Spain | Not Recruiting | 19 Jun 2023 | 100 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Salina Fisiológica Grifols 0,9% Solución para perfusión Cloruro de sodio | Comparator | SOLUCIÓN PARA PERFUSIÓN | INTRAVENOUS ADMINISTRATION | 36 | 1 | PRD1842798 |
Freeflex Ringer Lactato solución para perfusión | Test | SOLUCIÓN PARA PERFUSIÓN | INTRAVENIOUS INFUSION | 36 | 1 | PRD2085416 |