Ignite Creation Date:
2025-12-24 @ 4:35 PM
Ignite Modification Date:
2025-12-27 @ 9:06 PM
Study NCT ID:
NCT04475666
Status:
RECRUITING
Last Update Posted:
2025-09-08
First Post:
2020-06-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Replacing Protein Via Enteral Nutrition in Critically Ill Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016638', 'term': 'Critical Illness'}, {'id': 'D009748', 'term': 'Nutrition Disorders'}], 'ancestors': [{'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 2502}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-09-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2026-04-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-08-31', 'studyFirstSubmitDate': '2020-06-07', 'studyFirstSubmitQcDate': '2020-07-14', 'lastUpdatePostDateStruct': {'date': '2025-09-08', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2020-07-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-11-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Safety outcomes during ICU stay', 'timeFrame': 'ICU stay', 'description': 'New episode of stage 2 or higher AKI by KDIGO criteria; 2. Pneumonia defined as episodes of newly confirmed pneumonia according to the modified CDC criteria; 3. Grade IV Acute Gastrointestinal injury (AGI)'}, {'measure': 'Minor safety outcomes during ICU stay', 'timeFrame': 'ICU stay', 'description': 'Feeding tolerance; Diarrhoea; Refeeding syndrome'}], 'primaryOutcomes': [{'measure': '90 day-all cause mortality', 'timeFrame': '90 days', 'description': 'Mortality 90 days post randomization'}], 'secondaryOutcomes': [{'measure': 'Days alive at day 90 without life support', 'timeFrame': '90 days', 'description': 'use of vasopressor/inotropic support, invasive mechanical ventilation and/or renal replacement therapy'}, {'measure': 'Days alive and out of hospital at day 90', 'timeFrame': '90 days', 'description': '90 day survival after randomization'}, {'measure': 'Bacteremia until 2 days of ICU stay', 'timeFrame': 'until 2 days post ICU.', 'description': 'Any symptoms of bacteremia'}, {'measure': 'New or progression of Skin Pressure Ulcers', 'timeFrame': 'ICU stay', 'description': 'anytime during ICU stay'}, {'measure': 'Functional assessment at day 90', 'timeFrame': 'Day 90', 'description': 'SARC-F screen for sarcopenia and EuroQoL'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Critical Illness', 'Nutrition Disorders']}, 'referencesModule': {'references': [{'pmid': '28374096', 'type': 'BACKGROUND', 'citation': 'Arabi YM, Casaer MP, Chapman M, Heyland DK, Ichai C, Marik PE, Martindale RG, McClave SA, Preiser JC, Reignier J, Rice TW, Van den Berghe G, van Zanten ARH, Weijs PJM. The intensive care medicine research agenda in nutrition and metabolism. Intensive Care Med. 2017 Sep;43(9):1239-1256. doi: 10.1007/s00134-017-4711-6. Epub 2017 Apr 3.'}, {'pmid': '25733640', 'type': 'BACKGROUND', 'citation': 'Liebau F, Wernerman J, van Loon LJ, Rooyackers O. Effect of initiating enteral protein feeding on whole-body protein turnover in critically ill patients. Am J Clin Nutr. 2015 Mar;101(3):549-57. doi: 10.3945/ajcn.114.091934. Epub 2015 Feb 4.'}, {'pmid': '26773077', 'type': 'BACKGROUND', 'citation': 'McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016 Feb;40(2):159-211. doi: 10.1177/0148607115621863. No abstract available.'}, {'pmid': '28098623', 'type': 'BACKGROUND', 'citation': 'Compher C, Chittams J, Sammarco T, Nicolo M, Heyland DK. Greater Protein and Energy Intake May Be Associated With Improved Mortality in Higher Risk Critically Ill Patients: A Multicenter, Multinational Observational Study. Crit Care Med. 2017 Feb;45(2):156-163. doi: 10.1097/CCM.0000000000002083.'}, {'pmid': '25499096', 'type': 'BACKGROUND', 'citation': 'Weijs PJ, Looijaard WG, Beishuizen A, Girbes AR, Oudemans-van Straaten HM. Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients. Crit Care. 2014 Dec 14;18(6):701. doi: 10.1186/s13054-014-0701-z.'}, {'pmid': '29486907', 'type': 'BACKGROUND', 'citation': 'Koekkoek WACK, van Setten CHC, Olthof LE, Kars JCNH, van Zanten ARH. Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study. Clin Nutr. 2019 Apr;38(2):883-890. doi: 10.1016/j.clnu.2018.02.012. Epub 2018 Feb 17.'}, {'pmid': '27589411', 'type': 'BACKGROUND', 'citation': 'Arabi YM, Aldawood AS, Al-Dorzi HM, Tamim HM, Haddad SH, Jones G, McIntyre L, Solaiman O, Sakkijha MH, Sadat M, Mundekkadan S, Kumar A, Bagshaw SM, Mehta S; PermiT trial group. Permissive Underfeeding or Standard Enteral Feeding in High- and Low-Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial. Am J Respir Crit Care Med. 2017 Mar 1;195(5):652-662. doi: 10.1164/rccm.201605-1012OC.'}, {'pmid': '30260486', 'type': 'BACKGROUND', 'citation': 'Heyland DK, Patel J, Bear D, Sacks G, Nixdorf H, Dolan J, Aloupis M, Licastro K, Jovanovic V, Rice TW, Compher C. The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry-Based Randomized Trial: The EFFORT Trial. JPEN J Parenter Enteral Nutr. 2019 Mar;43(3):326-334. doi: 10.1002/jpen.1449. Epub 2018 Sep 27.'}, {'pmid': '38698442', 'type': 'DERIVED', 'citation': 'Arabi YM, Al-Dorzi HM, Aldibaasi O, Sadat M, Jose J, Muharib D, Algethamy H, Al-Fares AA, Al-Hameed F, Mady A, Kharaba A, Al Bshabshe A, Maghrabi K, AlGhamdi K, Rasool G, AlGhamdi A, Almekhlafi GA, Chalabi J, AlHumedi HI, Sakkijha MH, Alamrey NK, Alaskar AS, Alhutail RH, Sifaoui K, Alqahtani R, Qureshi AS, Hejazi MM, Arishi H, AlQahtani S, Ghazi AM, Baaziz ST, Azhar AO, Alabbas SF, AlAqeely M, AlOrabi O, Al-Mutawa A, AlOtaibi M, Elghannam MF, Almaani M, Buabbas SF, Alfilfil WAM, Alshahrani MS, Starkopf J, Preiser JC, Perner A, AlMubarak JH, Hazem WM, Albrahim T, Al-Dawood A; and the Saudi Critical Care Trials Group. Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial. Trials. 2024 May 2;25(1):296. doi: 10.1186/s13063-024-08105-w.'}, {'pmid': '37518058', 'type': 'DERIVED', 'citation': 'Arabi YM, Al-Dorzi HM, Sadat M, Muharib D, Algethamy H, Al-Hameed F, Mady A, AlGhamdi A, Almekhlafi GA, Al-Fares AA, Kharaba A, Al Bshabshe A, Maghrabi K, Al Ghamdi K, Rasool G, Chalabi J, AlHumedi HI, Sakkijha MH, Alamrey NK, Alhutail RH, Sifaoui K, Almaani M, Alqahtani R, Qureshi AS, Hejazi MM, Arishi H, AlQahtani S, Ghazi AM, Baaziz ST, Azhar AO, Alabbas SF, AlAqeely M, AlOrabi O, Al-Mutawa A, AlOtaibi M, Aldibaasi O, Jose J, Starkopf J, Preiser JC, Perner A, Al-Dawood A; Saudi Critical Care Trials Group. Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol. Trials. 2023 Jul 30;24(1):485. doi: 10.1186/s13063-023-07507-6.'}, {'pmid': '34930871', 'type': 'DERIVED', 'citation': 'Al-Dorzi HM, Stapleton RD, Arabi YM. Nutrition priorities in obese critically ill patients. Curr Opin Clin Nutr Metab Care. 2022 Mar 1;25(2):99-109. doi: 10.1097/MCO.0000000000000803.'}]}, 'descriptionModule': {'briefSummary': 'The investigator will investigate the effect of supplemental enteral protein (1.2 g/kg/day) added to standard formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge up to ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day), given in conjunction with similar amounts of stepwise caloric administration in the two groups on all-cause 90-day mortality.', 'detailedDescription': 'The REPLENISH is a multicentric, international, open label, randomized controlled trial which will enroll subjects in intensive care unit. Patients will be randomized on day 4 of ICU admission. Until ICU day 4, protein requirement will be provided according to the local practice as long as no intravenous amino acids are given and the average protein intake in the first 4 days does not exceed 0.8 g/kg/day. On ICU day 4, patients will be randomized to one of the two treatment groups: one with standard prescription without supplemental proteins (maximum1.2 g/kg/day) from the primary polymeric formula and another group will receive the standard amount of proteins (maximum 1.2 g/kg/day) from the primary polymeric formula AND supplemental protein at 1.2 g/kg/day.\n\nRandomization will be stratified by suspected COVID-19 and then by site and the use of renal replacement therapy at the time of randomization (intermittent hemodialysis or continuous renal replacement therapy.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria(on ICU calendar day 4 or the morning of day 5)\n\n1. Age ≥18-years old\n2. Patient started on enteral nutrition (EN) via nasogastric/orogastric or duodenal or percutaneous endoscopic gastrostomy (PEG) or jejunostomy tubes.\n3. The patient is on invasive mechanical ventilation and unlikely to be discharged from ICU next day.\n\nExclusion Criteria:\n\n1. Lack of commitment to full life support or brain death. Patients with "Do Not Resuscitate" order but with commitment to ongoing life support can be enrolled.\n2. Patients on any amount of parenteral nutrition (PN) in ICU at the time of screening, whether PN is used alone or in combination with enteral nutrition. Non-nutritional calories (dextrose, propofol, citrate) not considered as PN.\n3. Patients who received an average protein of more than 0.8g/kg/day in the first 4 ICU days.\n4. Patients being fed entirely through oral route - i.e. those who are eating.\n5. Pregnancy.\n6. Burn patients.\n7. Prisoners or those undergoing forced treatment.\n8. Patients with hepatic encephalopathy or Child C liver cirrhosis\n9. Inherited defect of amino acid metabolism.\n10. Allergies to protein supplement'}, 'identificationModule': {'nctId': 'NCT04475666', 'acronym': 'REPLENISH', 'briefTitle': 'Replacing Protein Via Enteral Nutrition in Critically Ill Patients', 'organization': {'class': 'OTHER', 'fullName': 'King Abdullah International Medical Research Center'}, 'officialTitle': 'Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients: An International, Multicenter Randomized Controlled Trial', 'orgStudyIdInfo': {'id': 'RC19/414/R'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Replenish protein group', 'description': 'The subjects randomized to this group will receive the standard amount of proteins (maximum 1.2 g/kg/day) from the primary polymeric formula AND supplemental protein at 1.2 g/kg/day', 'interventionNames': ['Other: Replenish protein group']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Standard protein group', 'description': 'The subjects randomized to this group will receive standard prescription without supplemental proteins (maximum1.2 g/kg/day) from the primary polymeric formula. No supplemental protein will be allowed', 'interventionNames': ['Other: Standard protein group']}], 'interventions': [{'name': 'Replenish protein group', 'type': 'OTHER', 'description': 'For patients with Body mass index(BMI) \\<30, use pre-ICU actual body weight(BW) for the calculation; if unavailable, use weight on ICU admission. For patients with BMI \\>=30, use adjusted body weight', 'armGroupLabels': ['Replenish protein group']}, {'name': 'Standard protein group', 'type': 'OTHER', 'description': 'For patients with BMI \\<30, use pre-ICU actual BW for the calculation; if unavailable, use weight on ICU admission. For patients with BMI \\>=30, use adjusted body weight', 'armGroupLabels': ['Standard protein group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '21423', 'city': 'Jeddah', 'state': 'Jeddah', 'status': 'RECRUITING', 'country': 'Saudi Arabia', 'contacts': [{'name': 'Fahad M Al-Hameed, MD', 'role': 'CONTACT', 'email': 'HameedF@ngha.med.sa', 'phone': '00966 12 2266666', 'phoneExt': '22771'}, {'name': 'Ohoud Al Orabi, MMedSC', 'role': 'CONTACT', 'email': 'alorabioh@NGHA.MED.SA', 'phone': '0096612 2266666', 'phoneExt': '28864'}, {'name': 'Fahad Al-Hameed, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'King Abdulaziz Medical city', 'geoPoint': {'lat': 21.49012, 'lon': 39.18624}}, {'zip': '11426', 'city': 'Riyadh', 'status': 'RECRUITING', 'country': 'Saudi Arabia', 'facility': 'Intensive Care Unit, King Abdulaziz Medical City', 'geoPoint': {'lat': 24.68773, 'lon': 46.72185}}], 'centralContacts': [{'name': 'Yaseen M Arabi, MD', 'role': 'CONTACT', 'email': 'arabi@ngha.med.sa', 'phone': '0118011111', 'phoneExt': '18855'}, {'name': 'Musharaf Sadat, MBBS', 'role': 'CONTACT', 'email': 'sadatmu@ngha.med.sa', 'phone': '0118011111', 'phoneExt': '10822'}], 'overallOfficials': [{'name': 'Yaseen M Arabi, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'King Saud Bin Abdulaziz University for Health Sciences'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'King Abdullah International Medical Research Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}