Ignite Creation Date:
2025-12-24 @ 11:14 PM
Ignite Modification Date:
2026-04-20 @ 2:55 AM
Study NCT ID:
NCT04381169
Status:
TERMINATED
Last Update Posted:
2022-03-21
First Post:
2020-05-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Aggressive Versus Non-aggressive Goal-directed Fluid Resuscitation in Acute Pancreatitis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010195', 'term': 'Pancreatitis'}], 'ancestors': [{'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077325', 'term': "Ringer's Lactate"}], 'ancestors': [{'id': 'D000077324', 'term': 'Crystalloid Solutions'}, {'id': 'D007552', 'term': 'Isotonic Solutions'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-05-05', 'size': 674795, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-03-04T00:05', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 249}}, 'statusModule': {'whyStopped': 'Increased frequency of fluid overload on the aggressive fluid resuscitation arm of treatment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2020-05-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-03', 'completionDateStruct': {'date': '2021-09-25', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-03-04', 'studyFirstSubmitDate': '2020-05-02', 'studyFirstSubmitQcDate': '2020-05-05', 'lastUpdatePostDateStruct': {'date': '2022-03-21', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-05-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-09-25', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Moderate-to-severe acute pancreatitis', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Moderate or severe category of the Revised Atlanta Classification (Banks et al, Gut 2013)'}], 'secondaryOutcomes': [{'measure': 'Death and/or persistent organ failure and/or infection of pancreatic necrosis', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Analyzed as a composite endpoint and each of its components, includes in-hospital mortality, persistent organ failure (according to the revised Atlanta classification, Banks et al, Gut 2013) or infection of pancreatic necrosis'}, {'measure': 'Fluid overload', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Fluid overload is defined by the absence of Acute Respiratory Distress Syndrome and at least 2 of the following 3 criteria (based on Sharma et al, Lancet Diabetes Endocrinol 2016, with modifications):\n\nCriteria 1. Hemodynamic-imaging evidence (≥1):\n\n* Non-invasive diagnostic evidence of heart failure (i.e., echocardiographic, cardiac MRI)\n* Radiographic evidence of pulmonary congestion\n* Invasive cardiac catheterization suggesting evidence of heart failure (i.e., pulmonary capillary wedge pressure \\[or left ventricular end-diastolic pressure\\] \\>18 mm Hg, right arterial pressure \\[or central venous pressure\\] \\>12 mm Hg, or cardiac index \\< 2·2 L/min per m2)\n\nCriteria 2. Heart failure symptoms (1):\n\n\\- Dyspnea\n\nCriteria 3. Heart failure signs (≥1):\n\n* Peripheral edema\n* Pulmonary rales or crackles, or crepitation\n* Increased jugular venous pressure, hepatojugular reflux, or both'}, {'measure': 'Shock', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Systolic blood pressure \\<90 mmHg after fluid resuscitation'}, {'measure': 'Respiratory failure', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'PaO2/FIO2\\<300'}, {'measure': 'Kidney failure', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Creatinine \\>1.9 mg/dL'}, {'measure': 'Local complications (acute peripancreatic fluid collections/ pancreatic necrosis/peripancreatic necrosis)', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'As described on the revised Atlanta classification, Banks et al, Gut 2013'}, {'measure': 'Length of hospital stay', 'timeFrame': 'From admission to discharge, up to 24 weeks'}, {'measure': 'Intensive care unit stay', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Need for intensive care unit (ICU) admission, and days admitted in the ICU'}, {'measure': 'Need for invasive treatment', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Endoscopic, percutaneous or surgical treatment of acute pancreatitis complications'}, {'measure': 'Need for nutritional support', 'timeFrame': 'From admission to discharge, up to 24 weeks', 'description': 'Need for enteral/parenteral feeding'}, {'measure': 'PAN-PROMISE scale', 'timeFrame': 'At 12, 24, 48 and 72 hours', 'description': 'Score on an acute pancreatitis Patient-Reported Outcome Measurement'}, {'measure': 'C-reactive protein', 'timeFrame': '48 and 72 hours', 'description': 'Blood levels of C-reactive protein'}, {'measure': 'Systemic inflammatory response syndrome (SIRS)', 'timeFrame': 'Baseline, 12, 24, 48 and 72 hours', 'description': 'SIRS at the different checkpoints. Presence of persistent (\\>48h) SIRS'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ["Acute pancreatitis; fluid resuscitation; therapy; outcomes; randomized controlled trial; Ringer lactate; Lactated Ringer's solution"], 'conditions': ['Acute Pancreatitis']}, 'referencesModule': {'references': [{'pmid': '23100216', 'type': 'BACKGROUND', 'citation': 'Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.'}, {'pmid': '36103415', 'type': 'DERIVED', 'citation': 'de-Madaria E, Buxbaum JL, Maisonneuve P, Garcia Garcia de Paredes A, Zapater P, Guilabert L, Vaillo-Rocamora A, Rodriguez-Gandia MA, Donate-Ortega J, Lozada-Hernandez EE, Collazo Moreno AJR, Lira-Aguilar A, Llovet LP, Mehta R, Tandel R, Navarro P, Sanchez-Pardo AM, Sanchez-Marin C, Cobreros M, Fernandez-Cabrera I, Casals-Seoane F, Casas Deza D, Lauret-Brana E, Marti-Marques E, Camacho-Montano LM, Ubieto V, Ganuza M, Bolado F; ERICA Consortium. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med. 2022 Sep 15;387(11):989-1000. doi: 10.1056/NEJMoa2202884.'}]}, 'descriptionModule': {'briefSummary': "WATERFALL is an investigator-initiated international multicenter open-label randomized clinical trial comparing aggressive versus moderate fluid resuscitation in acute pancreatitis. The main outcome variable will be the proportion of patients with moderate-to-severe AP. Aggressive fluid resuscitation will consist in Lactated Ringer Solution (LR) 20 ml/kg bolus (administered over 2 hours) followed by LR 3 ml/kg/h and moderate a LR bolus 10 ml/kg in case of hypovolemia or no bolus in patients with normal volemia, followed by LR 1.5 ml/kg/h. The patients will be assessed at 3 (±1), 12 (±4), 24 (±4), 48 (±4) and 72 (±4) hours from recruitment, and fluid resuscitation will be adjusted to the patient´s clinical and analytical status according to a protocol. Subgroup analysis will include patients with systemic inflammatory response syndrome (SIRS) at admission, with persistent (\\>48h) SIRS and with hypovolemia at admission.\n\nBased on available data (Sternby et al, Ann Surg 2019) we expect a 35% incidence of moderate to severe AP in the moderate arm. Sample sizes of 372 per arm of treatment (744 patients) achieve 80% power to detect a difference of 10% between the treatment arms at a significance level (alpha) of 0.05 using a two-sided z-testNA, assuming a 10% dropout. These results assume that 3 sequential tests are made using the O'Brien-Fleming spending function to determine the test boundaries.\n\nAll analyses will be performed on an intention-to-treat basis. The trial could be stop early for efficacy (primary end-point) if the observed two-sided P value is \\<0.0002 at the first interim analysis (after 1/3 of patients have been enrolled) or is \\<0.012 at second interim analysis (after 2/3 of patients have been enrolled), favoring aggressive fluid resuscitation. At final analysis, the hypothesis that the incidence of moderate-to-severe pancreatitis is similar in the two treatment arms will be rejected if p\\<0.046"}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Patients age greater or equal to 18 presenting to one of the collaborating centers\n* Diagnosis of acute pancreatitis according to the revised Atlanta classification which requires 2 of the following 3 criteria: A) Typical abdominal pain; B) Increase in serum amylase or lipase levels higher than 3 times the upper limit of normality; and C) Signs of AP in imaging.\n\nExclusion Criteria:\n\n* Uncontrolled arterial hypertension (systolic blood pressure \\>180 and/or diastolic blood pressure 100 mmHg);\n* New York Heart Association Class II hear failure (slight limitation of physical activity; fatigue, palpitations or dyspnea with ordinal physical activity) or worse, or ejection fraction\\<50% in the last echocardiography;\n* Decompensated cirrhosis (Child's Class B or C);\n* Hyper or hyponatremia (\\<135 or \\>145 mEq/l);\n* Hyperkalemia (\\>5 mEq/l);\n* Hypercalcemia (albumin or protein-corrected calcium\\>10.5 mg/dl);\n* Chronic kidney failure (basal glomerular filtration rate \\<60 mL/min/1.73m2);\n* Clinical signs or symptoms of volume overload or heart failure at recruitment (dyspnea, peripheral edema, pulmonary rales, or evident increased jugular ingurgitation at 45º);\n* Shock or respiratory failure according to the revised Atlanta classification at recruitment (non-fluid responding systolic blood pressure\\< 90 mmHg, PaO2/FIO2≤300 mmHg);\n* Time from pain onset to arrival to emergency room \\>24h;\n* Time from confirmation of pancreatitis to randomization \\>8h;\n* Severe comorbidity associated with an estimated life expectancy \\<1 year;\n* Confirmed chronic pancreatitis (in case of recurrent alcoholic pancreatitis a recent (\\<6 months) CT scan/MRI or endoscopic ultrasound is needed to rule out chronic pancreatitis"}, 'identificationModule': {'nctId': 'NCT04381169', 'acronym': 'WATERFALL', 'briefTitle': 'Aggressive Versus Non-aggressive Goal-directed Fluid Resuscitation in Acute Pancreatitis', 'organization': {'class': 'OTHER', 'fullName': 'Hospital General Universitario de Alicante'}, 'officialTitle': 'Effect of Early Weight-based Aggressive Versus Non-aggressive Goal-directed Fluid Resuscitation in the Early Phase of Acute Pancreatitis: an Open-label Multicenter Randomized-controlled Trial', 'orgStudyIdInfo': {'id': 'CEIM HGUA 2019/003'}, 'secondaryIdInfos': [{'id': 'PI19/01628', 'type': 'OTHER_GRANT', 'domain': 'Instituto de Salud Carlos III'}, {'id': '2019-000788-26', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Aggressive fluid resuscitation', 'description': 'Lactated Ringer Solution 20 ml/kg bolus (administered over 2 hours) followed by an infusion of 3 ml/kg/h.\n\nAt 12(±4) hours:\n\nA) Hypovolemia: same bolus and infusion B) No hypovolemia: infusion of lactated Ringer Solution 1.5 ml/kg/h C) Fluid overload: infusion rate of lactated Ringer Solution will be decreased or stopped\n\nSimilar adjustments are repeated at 24(±4), 48(±4) and 72(±4) hours\n\nFluid resuscitation is maintained at least 48h, and then it can be stopped in case of tolerating oral feeding for at least 8 hours', 'interventionNames': ['Drug: Lactated Ringer Solution']}, {'type': 'EXPERIMENTAL', 'label': 'Moderate fluid resuscitation', 'description': 'At recruitment:\n\nA) Hypovolemia: Lactated Ringer Solution 10 ml/kg bolus (administered over 2 hours) followed by an infusion of 1.5 ml/kg/h.\n\nB) No hypovolemia: infusion of lactated Ringer Solution of 1.5 ml/kg/h (no bolus).\n\nAt 12(±4) hours:\n\nA) Hypovolemia: same bolus and infusion B) No hypovolemia: infusion of lactated Ringer Solution 1.5 ml/kg/h C) Fluid overload: infusion rate of lactated Ringer Solution will be decreased or stopped\n\nSimilar adjustments are repeated at 24(±4), 48(±4) and 72(±4) hours\n\nFluid resuscitation can be stopped before the first 48h in case of tolerating oral feeding for at least 8 hours', 'interventionNames': ['Drug: Lactated Ringer Solution']}], 'interventions': [{'name': 'Lactated Ringer Solution', 'type': 'DRUG', 'otherNames': ['Aggressive fluid resuscitation', 'Moderate fluid resuscitation', 'Restrictive fluid resuscitation'], 'description': 'Comparison of aggressive versus moderate Lactated Ringer-based fluid resuscitation', 'armGroupLabels': ['Aggressive fluid resuscitation', 'Moderate fluid resuscitation']}]}, 'contactsLocationsModule': {'locations': [{'zip': '03010', 'city': 'Alicante', 'country': 'Spain', 'facility': 'Alicante', 'geoPoint': {'lat': 38.34517, 'lon': -0.48149}}, {'zip': '03550', 'city': 'Alicante', 'country': 'Spain', 'facility': 'Hospital General Universitario de Alicante', 'geoPoint': {'lat': 38.34517, 'lon': -0.48149}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Enrique de-Madaria', 'class': 'OTHER'}, 'collaborators': [{'name': 'Instituto de Salud Carlos III', 'class': 'OTHER_GOV'}, {'name': 'Asociación Española de Gastroenterología', 'class': 'OTHER'}, {'name': 'Asociación Española de Pancreatología', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator of the AUGH Clinical Pancreatology Research Group', 'investigatorFullName': 'Enrique de-Madaria', 'investigatorAffiliation': 'Hospital General Universitario de Alicante'}}}}