Ignite Creation Date:
2025-12-24 @ 10:13 PM
Ignite Modification Date:
2026-01-04 @ 4:17 PM
Study NCT ID:
NCT05076435
Status:
COMPLETED
Last Update Posted:
2022-03-25
First Post:
2021-09-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D007022', 'term': 'Hypotension'}, {'id': 'D004630', 'term': 'Emergencies'}], 'ancestors': [{'id': 'D007239', 'term': 'Infections'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D020969', 'term': 'Disease Attributes'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 124}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-11-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-03', 'completionDateStruct': {'date': '2022-03-19', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-03-24', 'studyFirstSubmitDate': '2021-09-11', 'studyFirstSubmitQcDate': '2021-09-30', 'lastUpdatePostDateStruct': {'date': '2022-03-25', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-10-13', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-12-19', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': '24-hour crystalloid iv. fluids', 'timeFrame': '24 hours from randomization', 'description': 'total amount of all administered intravenous, crystalloid fluids within 24 hours of randomization'}], 'secondaryOutcomes': [{'measure': 'Protocol violations', 'timeFrame': '24 hours from randomization', 'description': 'Feasibility measure: Number of patients with major protocol violations'}, {'measure': 'Screened-vs.-randomized-ratio', 'timeFrame': 'Through study completion, an average of 1 year', 'description': 'Feasibility measure: Number of patients screened vs included'}, {'measure': 'Time to inclusion', 'timeFrame': 'Through study completion, an average of 1 year', 'description': 'Feasibility measure: Time from admission to inclusion/randomization (hours)'}, {'measure': 'Lost-to-follow-up-rate', 'timeFrame': '24 hours from randomization', 'description': 'Feasibility measure: Number of patients lost to follow up in terms of 24-hour fluids'}, {'measure': 'Accumulated serious adverse reactions (SARs + SUSARs)', 'timeFrame': '7 days from randomization', 'description': 'Feasibility measure: Accumulated serious adverse reactions and events (SAEs + SARs+ SUSARs) within 7 days in-hospital'}, {'measure': 'Total 24-hour fluids', 'timeFrame': '24 hours from randomization', 'description': 'Total fluids (oral and intravenous) at 24 hours'}, {'measure': 'Mortality', 'timeFrame': 'Total of 90-days', 'description': 'In-hospital, 30- and 90-days mortality'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Sepsis', 'Hypotension', 'IV fluid therapy', 'Fluid resuscitation', 'Emergency Department', 'Crystalloids'], 'conditions': ['Sepsis']}, 'referencesModule': {'references': [{'pmid': '35652491', 'type': 'DERIVED', 'citation': 'Jessen MK, Andersen LW, Thomsen MH, Kristensen P, Hayeri W, Hassel RE, Messerschmidt TG, Solling CG, Perner A, Petersen JAK, Kirkegaard H. Restrictive fluids versus standard care in adults with sepsis in the emergency department (REFACED): A multicenter, randomized feasibility trial. Acad Emerg Med. 2022 Oct;29(10):1172-1184. doi: 10.1111/acem.14546. Epub 2022 Aug 5.'}, {'pmid': '35351214', 'type': 'DERIVED', 'citation': 'Jessen MK, Andersen LW, Thomsen MH, Kristensen P, Hayeri W, Hassel RE, Perner A, Petersen JAK, Kirkegaard H. Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)-protocol for a multicenter, randomized, clinical, proof-of-concept trial. Pilot Feasibility Stud. 2022 Mar 29;8(1):75. doi: 10.1186/s40814-022-01034-y.'}]}, 'descriptionModule': {'briefSummary': 'This is an investigator-initiated, multicenter, randomized, parallel-group, open-labeled, feasibility trial investigating volumes of fluid within 24 hours in 124 patients with sepsis allocated to two different IV fluid regimens enrolled at three emergency departments in Central Region Denmark. The primary outcome is total intravenous, crystalloid fluid volume within 24 hours and key secondary outcomes include protocol violations, total fluids (intravenous and oral) within 24 hours, SAEs/SUSARs, and inhospital-, 30- and 90-day mortality.', 'detailedDescription': 'BACKGROUND:\n\nSepsis is common in emergency department (ED) patients. Traditionally, intravenous (IV) fluids are used to optimise the circulation, and the use of higher volumes is recommended by international guidelines, but there are no recommendations for sepsis without hypotension or shock. Studies in septic shock seem to favour fluid restriction. Whether this is true in sepsis without hypotension/shock is unknown.\n\nOBJECTIVES:\n\nThe aim of the REFACED Sepsis trial is to test if an IV fluid restrictive protocol in ED patients with sepsis is feasible, i.e., if the protocol decreases the IV fluid volumes administered.\n\nDESIGN:\n\nREFACED Sepsis is a multicenter, randomized, parallel-group, open-labeled, feasibility trial\n\nPOPULATION:\n\nED patients with sepsis expected to be admitted for ≥ 24 hours\n\nEXPERIMENTAL INTERVENTION:\n\nIn the IV fluid restriction group no IV fluids should be given unless one of the below mentioned occurs;\n\nA fluid bolus of 250 ml isotonic crystalloid may be given within 15 minutes if one of the following occurs (hypoperfusion criteria):\n\n* Lactate concentration ≥ 4 mmol/l (arterial or venous blood gas/blood sample)\n* Hypotension (systolic BP \\< 90 mmHg)\n* Mottling beyond edge of kneecap (i.e., Mottling score \\>2)53\n* Severe oliguria, i.e., diuresis \\< 0.1 ml/kg/h, during the first 4 hours of admission\n\nAll patients will be ensured min. 1 L of oral/intravenous fluids in 24 hours and electrolytes can be corrected.\n\nCONTROL INTERVENTION:\n\nIn the usual care group there will be no upper limit for the use of IV fluids.\n\nOUTCOMES:\n\nThe primary outcome is 24-hour intravenous crystalloid fluid administration. Key secondary outcomes are: Feasibility measures: Number of patients with major protocol violations, Number of patients screened vs included, Time from admission to inclusion, Number of patients lost to follow up in terms of 24-hour fluids, Accumulated serious adverse reactions and events (SAEs + Suspected Unexpected Serious Adverse Reaction (SUSARs)) within 48 hours in-hospital, Total fluids (oral and intravenous) at 24 hours,\n\nTRIAL-SIZE:\n\n124 patients will be randomized to restrictive fluid administration or usual care within 24 hours of randomization'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria: All of the below must be fulfilled:\n\n1. Unplanned emergency department admission\n2. Age ≥ 18 years\n3. Sepsis defined as\n\n 1. suspected infection by the treating clinician AND\n 2. blood cultures drawn AND\n 3. IV antibiotics administered or planned AND\n 4. An infection related increase of SOFA\\*-score ≥ 2 from baseline\n4. Expected hospital stay \\> 24 hours as deemed by treating clinician\n\n * Sequential Organ Failure Assessment (SOFA) Score\n\nFurther more the patient must fulfill criteria for enrollment in an acute study according to Danish law\n\nExclusion Criteria: We will exclude patients fulfilling any of following exclusion criteria:\n\n1. ≥ 500 ml of fluids given prior to randomization\n2. Invasively ventilated or vasopressors initiated at the time of screening\n3. Known or suspected severe bleeding judged by the treating clinician\n4. Known or suspected pregnancy (women aged \\<45 years will have a pregnancy test performed before enrollment)\n5. Prior enrollment in the trial\n6. Patients, who the clinician expect not to survive the next 24-hours'}, 'identificationModule': {'nctId': 'NCT05076435', 'acronym': 'REFACED Sepsis', 'briefTitle': 'Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients', 'organization': {'class': 'OTHER', 'fullName': 'University of Aarhus'}, 'officialTitle': 'Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients - a Multicenter, Randomized Clinical Feasibility Trial (REFACED Sepsis)', 'orgStudyIdInfo': {'id': 'RECEM0001'}, 'secondaryIdInfos': [{'id': '2021-000224-35', 'type': 'EUDRACT_NUMBER'}, {'id': '1-10-72-163-21', 'type': 'OTHER', 'domain': 'The Committee on Health Research Ethics, Central Denmark Region'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Restrictive fluid administration', 'description': 'No IV fluids unless one of the extenuating circumstances occur;\n\n1. In case of severe hypoperfusion or severe circulatory impairment defined by either: 1) Lactate≥4 mmol/L, 2) Hypotension (systolic BP \\< 90 mmHg), 3) Mottling beyond the kneecap (mottling score \\>2) OR 4) Urinary output\\<0.1 mL/kg bodyweight/h (only in the first 4hrs after randomization) then a bolus of 250 ml of IV crystalloid solution may be given followed by re-evaluation\n2. In case of overt fluid losses (e.g. vomiting, large aspirates,) IV fluid may be given to correct for the loss, but not above the volume lost.\n3. In case the oral/enteral route for water or electrolyte solutions is contraindicated or has failed, IV fluids may be given to:\n\n Correct dehydration or electrolyte deficiencies Ensure a total fluid input of 1 L in 24hrs\n4. IV fluids may be given as carrier for medication, but with lowest possible volume', 'interventionNames': ['Drug: Isotonic crystalloids']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Usual care (standard care)', 'description': 'There will be no upper limit for the use of either IV or oral/enteral fluids\n\n1. IV fluids should be given in the case of hypoperfusion or circulatory impairment and should be continued as long as hemodynamic variables improve including static or dynamic variable(s) as chosen by the clinicians. These criteria are based on the Surviving Sepsis Campaign guideline.\n2. IV fluids should be given as maintenance if the ICU has a protocol recommending maintenance fluid\n3. IV fluids should be given to substitute expected or observed loss, dehydration or electrolyte derangements', 'interventionNames': ['Drug: Isotonic crystalloids']}], 'interventions': [{'name': 'Isotonic crystalloids', 'type': 'DRUG', 'description': 'Types of fluids in both intervention groups:\n\n* Fluids used for electrolyte disturbances: Fluids should be chosen to substitute the specific deficiency\n* Fluids given to substitute overt loss: Isotonic crystalloids are to be used. If large amounts of ascites are tapped, then human albumin may be used.\n* Blood products are only to be used on specific indications including severe bleeding, severe anaemia and prophylactic in case of severe coagulopathy.', 'armGroupLabels': ['Restrictive fluid administration', 'Usual care (standard care)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '8200', 'city': 'Aarhus', 'state': 'Central Jutland', 'country': 'Denmark', 'facility': 'Department of Emergency Medicine, Aarhus University Hospital', 'geoPoint': {'lat': 56.15674, 'lon': 10.21076}}, {'zip': '8930', 'city': 'Randers', 'state': 'Central Jutland', 'country': 'Denmark', 'facility': 'Department of Emergency Medicine, Regional Hospital Randers', 'geoPoint': {'lat': 56.4607, 'lon': 10.03639}}, {'zip': '8800', 'city': 'Viborg', 'state': 'Central Jutland', 'country': 'Denmark', 'facility': 'Department of Emergency Medicine, Regional Hospital Viborg', 'geoPoint': {'lat': 56.45319, 'lon': 9.40201}}], 'overallOfficials': [{'name': 'Marie K Jessen, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Denmark'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Marie Kristine Jessen, MD', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Aarhus', 'class': 'OTHER'}, {'name': 'Aarhus University Hospital', 'class': 'OTHER'}, {'name': 'Viborg Regional Hospital', 'class': 'OTHER'}, {'name': 'Randers Regional Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Marie Kristine Jessen, MD', 'investigatorAffiliation': 'University of Aarhus'}}}}