Normal Saline Versus Lactated Ringer's Solution for Acute Pancreatitis Resuscitation
- Conditions
- Acute Pancreatitis
- Interventions
- Drug: Lactated Ringer SolutionDrug: Normal saline
- Registration Number
- NCT05781243
- Lead Sponsor
- Enrique de-Madaria
- 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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 792
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lactated Ringer solution (LR) Lactated Ringer Solution 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. Normal saline (NS) Normal saline NS: Normal Saline. Patients in the NS treatment arm will receive fluid therapy based on normal saline for a minimum of 48 hours.
- Primary Outcome Measures
Name Time Method Number of Participants with moderately severe or severe acute pancreatitis From date of randomization until 30 days after randomization 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)
- Secondary Outcome Measures
Name Time Method Number of participants with local complications From date of randomization until 30 days after randomization Presence of acute peripancreatic fluid collections, acute necrotic collection, pseudocyst, walled-off necrosis, gastric outlet dysfunction, splenic or portal vein thrombosis, and colonic necrosis according to the revised Atlanta Classification (https://doi.org/10.1136/gutjnl-2012-302779).
Number of participants with necrotizing pancreatitis From date of randomization until 30 days after randomization Presence of acute necrotic collections according to the revised Atlanta Classification (https://doi.org/10.1136/gutjnl-2012-302779).
Number of participants with infection of pancreatic collections or necrosis From date of randomization until 30 days after randomization Extraluminal gas in the pancreatic and/or peripancreatic tissues on CT scan or when a sample from the collection/necrosis contains pus or is positive for bacteria and/or fungi on Gram stain or culture.
Number of participants with systemic inflammatory response syndrome At 24 and 48 hours At least 2 criteria: A) pulse \>90 beats/min, B) respirations \>20/min or arterial blood PaCO2 \<32 mm Hg, C) temperature \<36°C or \>38°C, D) white blood cell count \<4,000 cells/mm3 or \>12,000 cells/mm3 or \>10% bands
Number of systemic inflammatory response syndrome criteria At 24 and 48 hours The criteria are: A) pulse \>90 beats/min, B) respirations \>20/min or arterial blood PaCO2 \<32 mm Hg, C) temperature \<36°C or \>38°C, D) white blood cell count \<4,000 cells/mm3 or \>12,000 cells/mm3 or \>10% bands
PAN-PROMISE symptom scale At 24 and 48 hours (final value and change from baseline) PAN-PROMISE scale: a 7-symptom scale patient-reported outcome (range, 0 to 10 for each symptom; overall range, 0 to 70, with higher scores indicating higher symptom intensity). Details: https://doi.org/10.1136/gutjnl-2020-320729
Time to oral refeeding From date of randomization until 30 days after randomization Days from baseline to oral refeeding
Number of participants with invasive treatment From date of randomization until 30 days after randomization Any of the following: thoracocentesis due to pancreatitis-induced pleural effusion, percutaneous and/or endoscopic drainage of pancreatic or peripancreatic fluid collections or necrosis, endoscopic or surgical necrosectomy, endoscopic retrograde cholangiopancreatography due to A) ruptured common bile duct, B) jaundice caused by compression of the common bile duct, C) main pancreatic duct leakage
Number of participants with nutritional support From date of randomization until 30 days after randomization Use of enteral (nasogastric or nasojejunal) or parenteral feeding
Number of participants with intensive care unit admission From date of randomization until 30 days after randomization Admission in the intensive care unit
Number of participants with exacerbation of coexisting condition From date of randomization until 30 days after randomization Exacerbation of pre-existing co-morbidity. The definition provided by the Revised Atlanta Classification is " Exacerbation of pre-existing co-morbidity, such as coronary artery disease or chronic lung disease, precipitated by the acute pancreatitis is defined as a systemic complication. In this document, we distinguish between persistent organ failure (the defining feature of severe acute pancreatitis) and other systemic complications, which are an exacerbation of pre-existing co-morbid disease." (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779) For the WATERLAND trial we define exacerbation of pre-existing co-morbidity as
Number of participants with any organ failure From date of randomization until 30 days after randomization Definition according to the revised Atlanta classification (https://doi.org/10.1136/gutjnl-2012-302779): organ failure is defined by the presence of any of the following criteria: A) kidney failure as a creatinine ≥1.9 mg/dL or \>170 micromol/L, B) cardiovascular failure as a systolic blood pressure \<90 mmHg despite fluid resuscitation, and C) respiratory failure as a PaO2/FIO2≤300
Number of participants with persistent organ failure From date of randomization until 30 days after randomization Organ failure lasting more than 48h (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)
Number of participants with shock From date of randomization until 30 days after randomization Systolic blood pressure \<90 mmHg despite fluid resuscitation (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)
Number of participants with respiratory failure From date of randomization until 30 days after randomization PaO2/FIO2≤300 (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)
Number of participants with kidney failure From date of randomization until 30 days after randomization Creatinine ≥1.9 mg/dL or \>170 micromol/L (revised Atlanta classification: https://doi.org/10.1136/gutjnl-2012-302779)
Mortality (number of participants) From date of randomization until 30 days after randomization Death
Hospital stay From date of randomization until 30 days after randomization Days from recruitment to discharge from index admission
C-reactive protein At 48 hours from randomization C-reactive protein blood levels
Number of participants with hypovolemia At 24 and 48 hours from randomization WATERFALL trial criteria for hypovolemia (see https://www.nejm.org/doi/10.1056/NEJMoa2202884)
Number of participants with fluid overload From randomization to 72 h thereafter WATERFALL trial criteria for fluid overload (see https://www.nejm.org/doi/10.1056/NEJMoa2202884)
Number of participants with acute kidney injury At 24 and 48 hours from randomization KDIGO criteria: increase in serum creatinine of ≥0.3 mg/dL within 48 hr or ≥50% within 7 days or urine output of \<0.5 mL/kg/hr for \>6 hr (https://doi.org/10.1159/000339789)
Number of participants with hyperkalemia At 24 and 48 hours from randomization Venous potassium\>5mEq/L
Number of participants with hypercalcemia At 24 and 48 hours from randomization Venous calcium corrected by proteins\>10.5mg/dL or 2.62 mmol/L
Number of participants with hyperchloremia At 24 and 48 hours from randomization Venous chloride\>106mEq/L
Number of participants with acidosis At 24 and 48 hours from randomization Venous blood pH \<7.35
Number of participants with hyperchloremic acidosis At 24 and 48 hours from randomization Patients with venous chloride\>106mEq/L and venous blood pH \<7.35
Number of participants with composite safety outcome (primary safety outcome) At 24 and 48 hours from randomization Fluid overload or acute kidney injury or hyperkalemia or hypercalcemia or hyperchloremia or acidosis
Trial Locations
- Locations (1)
Dr. Balmis General University Hospital
🇪🇸Alicante, Spain