Comparative Efficacy of Normal Saline and Lactated Ringer's Solution in Fluid Resuscitation for Acute Pancreatitis: A Multicenter Randomized Controlled Trial

The primary objective of the WATERLAND trial is to evaluate the efficacy of **fluid therapy** using normal saline versus lactated Ringer's solution in the early management of **Acute Pancreatitis** (AP). This study aims to determine if one of these treatment arms leads to a better clinical outcome in patients with AP. Given that fluid therapy is a cost-effective and universally available treatment, demonstrating a superior option could significantly impact the management of this common condition. The trial does not specify any secondary objectives.

The clinical trial focuses on individuals diagnosed with **acute pancreatitis**, aiming to enhance early management through fluid therapy. The study population includes both male and female participants, aged 18 years and older, without any specific vulnerable populations being targeted. Participants were selected based on a confirmed diagnosis of acute pancreatitis, as defined by the revised Atlanta classification, which includes criteria such as typical abdominal pain, elevated serum amylase or lipase levels, and imaging signs of the condition. The sponsor has not provided information regarding the total number of participants. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include being at least 18 years of age and providing informed consent. The study does not focus on any specific health status beyond the diagnosis of acute pancreatitis.

The clinical trial is designed to evaluate the effectiveness and safety of **Ringer's lactate** and **Normal Saline** solutions in the management of **acute pancreatitis**. This is a low-intervention, open-label, multicenter, randomized controlled trial. The trial will compare the two solutions, which are commonly used for fluid resuscitation in acute pancreatitis, to determine their impact on the progression of the disease. The study is expected to commence on April 2, 2024, and conclude by May 1, 2025, with a maximum treatment period of 7 days for each participant.

Participants will be randomly assigned to receive either Ringer's lactate or Normal Saline solution via infusion. The trial will follow a double-blind methodology to ensure unbiased results. The primary outcome will focus on the incidence of moderately severe to severe acute pancreatitis, as defined by the revised Atlanta classification. Safety outcomes will include monitoring for fluid overload, acute kidney injury, hyperkalemia, hypercalcemia, and acidosis.

The sequence of study visits includes an initial screening visit to confirm eligibility, based on criteria such as age (18 years or older) and a diagnosis of acute pancreatitis. Participants must provide informed consent to be included in the study. Follow-up visits will be scheduled to monitor the participants' response to treatment and to assess any adverse events. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.

Participant involvement is expected to last up to 7 days, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or withdrawal of consent by the participant. The trial aims to provide valuable insights into the optimal fluid therapy for acute pancreatitis, potentially influencing future treatment guidelines.

The clinical trial involves the administration of two experimental medications, both in the form of **solution for infusion**. The first experimental medication is "Ringer Laktát Hartmann 'Baxter' oldatos infúzió," which contains the active substances **potassium chloride**, **sodium chloride**, **calcium chloride dihydrate**, and **sodium lactate**. This solution is administered via infusion, with a maximum daily dose of 4000 ml and a total maximum dose of 28000 ml over a treatment period of up to 7 days. The product is manufactured by Baxter Hungary Kft. and is classified under the ATC code B05BB01, indicating its use as an electrolyte solution.

The second experimental medication is "Nátrium-klorid EUROLIFE 0,9% oldatos infúzió," which contains **sodium chloride** as its active substance. This solution is also administered via infusion, with the same dosing parameters as the first medication: a maximum daily dose of 4000 ml and a total maximum dose of 28000 ml over a 7-day treatment period. This product is manufactured by Eurolife Healthcare Hungary Kft. and shares the same ATC classification as the first medication, B05BB01, denoting its role as an electrolyte solution.

Both medications are used in the context of the WATERLAND trial, which aims to evaluate the efficacy of these solutions in the management of acute pancreatitis. The trial is designed to determine if one of these treatment arms results in a better clinical outcome for patients with this condition. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The efficacy of the clinical trial titled "Normal saline versus lactated Ringer’s solution for fluid administration in acute pancreatitis, an open-label multicenter randomized controlled trial: the WATERLAND trial" will be assessed using specific endpoints. The primary efficacy endpoint is the occurrence of moderately severe to severe **acute pancreatitis** (AP), as defined by the revision of the Atlanta classification. This classification requires at least two of the following criteria: typical abdominal pain, an increase in serum amylase or lipase levels higher than three times the upper limit of normality, or signs of acute pancreatitis in imaging. The primary safety outcome is a composite variable that includes fluid overload, acute kidney injury, hyperkalemia, hypercalcemia, or acidosis.

The trial aims to evaluate the effectiveness and safety of Ringer's lactate solution compared to normal saline solution in the management of acute pancreatitis. The study is designed as a low-interventional pharmacological randomized controlled trial, given that both solutions have been used in clinical practice for over a century. The trial will provide insights into the better evolution of pancreatitis with one of the treatment arms, potentially influencing the treatment approach for this condition. The trial is expected to conclude by May 2025, with recruitment starting in April 2024.