Normal saline versus lactated Ringer’s solution for acute pancreatitis resuscitation, an open-label multicenter randomized controlled trial: the WATERLAND trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital General Universitario Dr. Balmis

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

completed 30 Aug 2024

Decision date (initial)

2024-01-11

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III

External identifiers

EU CT number

2023-509879-16-00

EudraCT number

2023-000010-18

ClinicalTrials.gov

NCT05781243

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main objective of the trial is to investigate the effect of lactated Ringer solution compared to normal saline on the severity and safety of acute pancreatitis. The main efficacy endpoint is the frequency of moderately severe to severe acute pancreatitis according to the revision of the Atlanta classification. The main safety endpoint is a compound variable: fluid overload or acute kidney injury or hyperkalemia or hypercalcemia or acidosis.

Secondary objectives 1

1. The secondary objectives of the trial are to investigate the effect of lactated Ringer solution compared to normal saline on the secondary efficacy and safety endpoints.

Conditions and MedDRA coding

Acute pancreatitis

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Patient is 18 years or older
2. 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
3. Signature of informed consent

Exclusion criteria 11

1. 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
2. Decompensated cirrhosis (Child’s class B or C)
3. Hyper or hyponatremia (<135 or >145 mEq/L)
4. Hyperkalemia (>5 mEq/L)
5. Hypercalcemia (albumin or protein-corrected calcium >10.5 mg/dL or 2.62 mmol/L)
6. 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
7. 7. Signs of volume overload or heart failure at recruitment (peripheral edema, pulmonary rales, or increased jugular ingurgitation at 45º)
8. Time from pain onset to arrival to emergency room >24 h
9. Time from confirmation of pancreatitis to randomization >8 h
10. Chronic pancreatitis defined by a Wirsung duct ≥4mm and/or pancreatic calcifications
11. 11. More than 1 previous episode of acute pancreatitis (only 2 episodes of acute pancreatitis are allowed, one of them the present episode)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome will be moderately severe to severe AP, according to the RAC. (Atlanta classification) within the first 30 days after randomization.

Secondary endpoints 1

1. Local complications (specific complications will be also recorded) Necrotizing pancreatitis SIRS Number of SIRS criteria PAN-PROMISE symptom scale Time to oral refeeding Invasive treatment Nutritional support Intensive care unit admission Exacerbation of coexisting condition Any organ failure Persistent organ failure Shock Respiratory failure Kidney failure Death Hospital stay C-reactive protein

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital General Universitario Dr. Balmis

Sponsor organisation

Hospital General Universitario Dr. Balmis

Address

Avinguda Del Pintor Baeza 12

City

Alicante

Postcode

03010

Country

Spain

Scientific contact point

Organisation

Hospital General Universitario Dr. Balmis

Contact name

Alicia Vaillo

Public contact point

Organisation

Hospital General Universitario Dr. Balmis

Contact name

Alicia Vaillo

Locations

1 EU/EEA country · 27 investigational sites

By country

Investigational sites

Application history

4 submissions — initial application plus substantial / non-substantial modifications