Ignite Creation Date:
2025-12-25 @ 2:09 AM
Ignite Modification Date:
2025-12-26 @ 6:35 PM
Study NCT ID:
NCT05124860
Status:
COMPLETED
Last Update Posted:
2025-04-11
First Post:
2021-10-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Longitudinal Investigation of Energy Expenditure and Substrate Utilization in Critically Ill Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016638', 'term': 'Critical Illness'}], 'ancestors': [{'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2025-04-08', 'size': 272628, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_002.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2025-04-09T10:34', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 714}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-02-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'completionDateStruct': {'date': '2025-03-21', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-04-09', 'studyFirstSubmitDate': '2021-10-25', 'studyFirstSubmitQcDate': '2021-11-15', 'lastUpdatePostDateStruct': {'date': '2025-04-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-11-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-07-18', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Correlations between energy expenditure/respiratory quotient and markers of inflammation, protein catabolism, antecedent characteristics and outcomes.', 'timeFrame': 'From date of ICU admission to the date of ICU discharge or death, whichever came first, assessed up to 24 months.', 'description': 'CRP, albumin, urea/creatinine ratio, age, sex, SOFA, ICU mortality.'}], 'primaryOutcomes': [{'measure': 'Change in resting energy expenditure over time in patients who stay in ICU for >10 days.', 'timeFrame': 'From date of ICU admission to the date of ICU discharge or death, whichever came first, assessed up to 24 months.', 'description': 'Kcal/kg adjusted body weight/24 hours.'}], 'secondaryOutcomes': [{'measure': 'Change in respiratory quotient over time in patients who stay in ICU for >10 days.', 'timeFrame': 'From date of ICU admission to the date of ICU discharge or death, whichever came first, assessed up to 24 months.', 'description': 'Quotient of carbon dioxide production and oxygen consumption.'}, {'measure': 'Change in resting energy expenditure (kcal/kg/day) over time in patients who stay in ICU for ≤10 days.', 'timeFrame': 'From date of ICU admission to the date of ICU discharge or death, whichever came first, assessed up to 24 months.', 'description': 'Kcal/kg adjusted body weight/24 hours.'}, {'measure': 'Change in respiratory quotient over time in patients who stay in ICU for ≤10 days.', 'timeFrame': 'From date of ICU admission to the date of ICU discharge or death, whichever came first, assessed up to 24 months.', 'description': 'Quotient of carbon dioxide production and oxygen consumption.'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Energy expenditure', 'Indirect calorimetry', 'Metabolism', 'Prolonged critical illness'], 'conditions': ['Critical Illness']}, 'referencesModule': {'references': [{'pmid': '24970271', 'type': 'BACKGROUND', 'citation': 'Preiser JC, Ichai C, Orban JC, Groeneveld AB. Metabolic response to the stress of critical illness. Br J Anaesth. 2014 Dec;113(6):945-54. doi: 10.1093/bja/aeu187. Epub 2014 Jun 26.'}, {'pmid': '27155770', 'type': 'BACKGROUND', 'citation': 'Iwashyna TJ, Hodgson CL, Pilcher D, Bailey M, van Lint A, Chavan S, Bellomo R. Timing of onset and burden of persistent critical illness in Australia and New Zealand: a retrospective, population-based, observational study. Lancet Respir Med. 2016 Jul;4(7):566-573. doi: 10.1016/S2213-2600(16)30098-4. Epub 2016 May 4.'}, {'pmid': '31531715', 'type': 'BACKGROUND', 'citation': 'Haines RW, Zolfaghari P, Wan Y, Pearse RM, Puthucheary Z, Prowle JR. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019 Dec;45(12):1718-1731. doi: 10.1007/s00134-019-05760-5. Epub 2019 Sep 17.'}, {'pmid': '31919541', 'type': 'BACKGROUND', 'citation': 'Nakamura K, Ogura K, Nakano H, Naraba H, Takahashi Y, Sonoo T, Hashimoto H, Morimura N. C-reactive protein clustering to clarify persistent inflammation, immunosuppression and catabolism syndrome. Intensive Care Med. 2020 Mar;46(3):437-443. doi: 10.1007/s00134-019-05851-3. Epub 2020 Jan 9.'}], 'seeAlsoLinks': [{'url': 'https://portal.icuregswe.org/utdata/', 'label': 'Reporting on length of ICU stay 2015-2019 from the Swedish ICU Registry database.'}]}, 'descriptionModule': {'briefSummary': 'The metabolic alterations associated with critical illness have significant implications for the nutritional management of ICU patients. Despite this, little is known about these changes in patients requiring prolonged organ support and nutritional therapy.\n\nThe overall aim of this study is to describe changes in metabolism over time in a large prospective cohort of patients requiring \\>10 days of ICU care. Our hypothesis is that there is a significant change in mean energy expenditure and respiratory quotient (RQ) between the early (day 1-3), intermediate (day 4-10) and late (\\>10 days) phase in ICU.', 'detailedDescription': 'Background\n\nCritical illness has profound effects on human metabolism. The most prominent feature in the early phase is an upregulation of catabolic pathways, which promotes the production of endogenous energy substrates and net protein breakdown \\[1\\].\n\nThere is very little published data describing trends of energy expenditure and substrate utilization in patients with a prolonged ICU stay. While this group only constitutes a small fraction of ICU patients, it accounts for a large part of ICU resource allocation, morbidity and mortality \\[2\\]. Several studies have been conducted in recent years to better characterize patients with persistent critical illness, focusing on markers of catabolism and inflammation \\[3, 4\\]. It is not known if these changes are associated with alterations in energy metabolism and substrate utilization.\n\nBridging these knowledge gaps will improve our understanding of the nutritional needs and metabolism of patients beyond the early phase in ICU. We therefore plan to conduct a prospective observational multi-center study to address these questions.\n\nAim and hypothesis\n\nThe overall aim of this project is to describe longitudinal changes in energy expenditure and associated clinical characteristics in a large cohort of patients with a prolonged ICU stay. Our hypothesis is that there is a significant change in mean energy expenditure and respiratory quotient (RQ) between the early (day 1-3), intermediate (day 4-10) and late (\\>10 days) phase in ICU. Correlations between metabolic rate and other clinical characteristics will also be analysed for hypothesis-generating purposes.\n\nPopulation\n\nAll adult ICU patients with at least one measurement of energy expenditure by indirect calorimetry at participating study sites will be included in the study. Study sites are encouraged to routinely perform indirect calorimetry every 3-4 days. Study subjects will be followed until ICU discharge or death, whichever comes first.\n\nData collection and reporting\n\nPatient data will be reported pseudonymized through a secure online form.\n\nOn admission\n\n* Admission date\n* Admission diagnosis (ICD-10)\n* Surgery prior to admission (YES/NO), elective or emergent\n* Outcome prediction score (SAPS 3, APACHE III/IV, MPM, etc.) and risk of death on admission (%)\n* ICU source admission (ER/ward/OT/other ICU)\n* Days in hospital before ICU admission\n\nDemographic and anthropometric data:\n\n* Sex (male/female)\n* Age (years)\n* Weight (kg)\n* Height (cm)\n\nChronic comorbidities registered in electronic health records (YES/NO):\n\n* Hypertension\n* Ischemic heart disease\n* Heart failure\n* Diabetes mellitus\n* COPD\n* Chronic kidney disease\n* End-stage renal disease\n* Liver cirrhosis\n* Active cancer (not in complete remission)\n* Haematological malignancy\n* Solid organ transplant\n\nOn the day of each indirect calorimetry\n\n* REE (kcal/24 h), RQ, VO2 (ml/min), VCO2 (ml/min) and date of investigation\n* Invasive mechanical ventilation (YES/NO) or renal replacement therapy (YES/NO)\n\nIf YES to invasive mechanical ventilation:\n\n* Fraction of inspired oxygen\n* Positive end-expiratory pressure (cmH2O)\n\nFactors that may influence REE:\n\n* Sequential organ failure assessment (SOFA) score\n* Fever (≥38.5 ℃) within 2h of measurement (YES/NO/MISSING)\n* Richmond Agitation-Sedation Scale score\n\nResults of daily blood tests if available from routine testing:\n\n* P-CRP (mg/L)\n* P-albumin (g/L)\n* P-urea (mmol/L)\n* P-creatinine (μmol/L)\n* Haemoglobin (g/L)\n\nMedications, nutrition and other therapies:\n\n* Infusions of vasoactive medications (YES/NO, if YES → name of medication(s))\n* Infusions of sedatives or analgesics (YES/NO, if YES → name of medication(s), if propofol → infusion rate at time of measurement)\n* Infusions of parenteral and/or enteral nutrition (YES/NO, if YES → brand name, formulation and rate at time of measurement)\n\nOn discharge\n\n* Discharge date\n* Survival status (ALIVE/DEAD)\n* Sepsis during ICU stay (NO/SEPSIS/SEPTIC SHOCK)\n\nSample size considerations\n\nThe goal of this study is to include ≥200 patients with an ICU length of stay of \\>10 days. Based on data from the Swedish Intensive Care Registry between 2015-2019, these patients accounted for 5% of all ICU admissions \\[5\\]. This proportion is comparable to results from a registry study conducted in Australia and New Zealand of over one million ICU admissions \\[2\\]. Based on these figures we intend to screen 6000 unique patients for study participation, accounting for the possibility that multiple measurements of indirect calorimetry are not consistently performed. In total we expect to include around 1250 unique subjects with at least one measurement with indirect calorimetry.\n\nStatistics\n\nDescriptive data will be presented as mean +/- standard deviation or median (interquartile range) as appropriate. The primary and secondary outcome measures will be analysed using a generalized linear mixed-effects model. Exploratory outcomes and their association to other clinical variables will be analysed using generalized linear regression models. If values are found to be not missing at random, conditional logistic regression censoring will be used to calculate inverse probability weights for accounting for difference in drop-out probabilities.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Adult intensive care unit patients with ≥1 measurement of energy expenditure by indirect calorimetry.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. \\>/= 18 years old.\n2. Admitted to the ICU of a participating study site.\n3. At least one measurement of energy expenditure performed during ICU stay.\n\nExclusion Criteria:\n\n1. Patients readmitted to the ICU of a participating study site \\>72 hours after ICU discharge and already included in the study (≥1 measurement of energy expenditure performed during prior admission). If a patient is readmitted within ≤72 hours of ICU discharge this is considered a continuation of the last ICU admission for the purposes of this study.\n2. Burns \\>20% of body surface area.\n3. Pregnancy.'}, 'identificationModule': {'nctId': 'NCT05124860', 'acronym': 'EPIC', 'briefTitle': 'A Longitudinal Investigation of Energy Expenditure and Substrate Utilization in Critically Ill Patients', 'organization': {'class': 'OTHER', 'fullName': 'Karolinska University Hospital'}, 'officialTitle': 'A Longitudinal Investigation of Energy Expenditure and Substrate Utilization in Critically Ill Patients: a Prospective Observational Multi-center Study', 'orgStudyIdInfo': {'id': 'K 2021-6909'}}, 'armsInterventionsModule': {'interventions': [{'name': 'Indirect calorimetry', 'type': 'DIAGNOSTIC_TEST', 'description': 'Measurement of metabolic rate (kcal/day) by respiratory gas analysis.'}]}, 'contactsLocationsModule': {'locations': [{'city': 'Melbourne', 'country': 'Australia', 'facility': 'Royal Melbourne Hospital', 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}, {'city': 'Melbourne', 'country': 'Australia', 'facility': 'The Alfred', 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}, {'city': 'Ede', 'country': 'Netherlands', 'facility': 'Gelderse Vallei Hospital', 'geoPoint': {'lat': 52.03333, 'lon': 5.65833}}, {'zip': '14186', 'city': 'Huddinge', 'state': 'Stockholm County', 'country': 'Sweden', 'facility': 'Karolinska University Hospital', 'geoPoint': {'lat': 59.23705, 'lon': 17.98192}}, {'city': 'Örebro', 'country': 'Sweden', 'facility': 'Universitetssjukhuset Örebro', 'geoPoint': {'lat': 59.27412, 'lon': 15.2066}}, {'city': 'Stockholm', 'country': 'Sweden', 'facility': 'Capio S:t Görans Sjukhus', 'geoPoint': {'lat': 59.32938, 'lon': 18.06871}}, {'city': 'Lucerne', 'country': 'Switzerland', 'facility': 'Lucerne Cantonal Hospital', 'geoPoint': {'lat': 47.05048, 'lon': 8.30635}}], 'overallOfficials': [{'name': 'Martin Sundström Rehal, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Karolinska University Hospital'}, {'name': 'Olav Rooyackers, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Karolinska Institutet'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Karolinska University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Karolinska Institutet', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Martin Sundstrom Rehal', 'investigatorAffiliation': 'Karolinska University Hospital'}}}}