Normal Saline Versus Lactated Ringer's Solution for Acute Pancreatitis Resuscitation, an Open-label Multicenter Randomized Controlled Trial: the WATERLAND Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 812
- 试验地点
- 2
- 主要终点
- Number of Participants with moderately severe or severe acute pancreatitis
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Lactated Ringer Solution (Drug)
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.
干预措施: Normal saline (Drug)
结局指标
主要结局
Number of Participants with moderately severe or severe acute pancreatitis
时间窗: 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)
次要结局
- Number of participants with local complications(From date of randomization until 30 days after randomization)
- Number of participants with necrotizing pancreatitis(From date of randomization until 30 days after randomization)
- Number of participants with infection of pancreatic collections or necrosis(From date of randomization until 30 days after randomization)
- Number of participants with systemic inflammatory response syndrome(At 24 and 48 hours)
- Number of systemic inflammatory response syndrome criteria(At 24 and 48 hours)
- PAN-PROMISE symptom scale(At 24 and 48 hours (final value and change from baseline))
- Time to oral refeeding(From date of randomization until 30 days after randomization)
- Number of participants with invasive treatment(From date of randomization until 30 days after randomization)
- Number of participants with nutritional support(From date of randomization until 30 days after randomization)
- Number of participants with intensive care unit admission(From date of randomization until 30 days after randomization)
- Number of participants with exacerbation of coexisting condition(From date of randomization until 30 days after randomization)
- Number of participants with any organ failure(From date of randomization until 30 days after randomization)
- Number of participants with persistent organ failure(From date of randomization until 30 days after randomization)
- Hospital stay(From date of randomization until 30 days after randomization)
- Number of participants with shock(From date of randomization until 30 days after randomization)
- Number of participants with respiratory failure(From date of randomization until 30 days after randomization)
- Number of participants with kidney failure(From date of randomization until 30 days after randomization)
- Mortality (number of participants)(From date of randomization until 30 days after randomization)
- C-reactive protein(At 48 hours from randomization)
- Number of participants with hypovolemia(At 24 and 48 hours from randomization)
- Number of participants with fluid overload(From randomization to 72 h thereafter)
- Number of participants with acute kidney injury(At 24 and 48 hours from randomization)
- Number of participants with hyperkalemia(At 24 and 48 hours from randomization)
- Number of participants with hypercalcemia(At 24 and 48 hours from randomization)
- Number of participants with hyperchloremia(At 24 and 48 hours from randomization)
- Number of participants with acidosis(At 24 and 48 hours from randomization)
- Number of participants with hyperchloremic acidosis(At 24 and 48 hours from randomization)
- Number of participants with composite safety outcome (primary safety outcome)(At 24 and 48 hours from randomization)
研究者
Enrique de-Madaria
Principal Investigator of clinical pancreatology research group-ERICA consortium, ISABIAL
Hospital General Universitario de Alicante