Ignite Creation Date:
2025-12-24 @ 5:25 PM
Ignite Modification Date:
2025-12-24 @ 5:25 PM
Study NCT ID:
NCT04339868
Status:
UNKNOWN
Last Update Posted:
2021-09-24
First Post:
2020-04-07
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Terlipressin for Refractory Septic Shock
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012772', 'term': 'Shock, Septic'}, {'id': 'D012769', 'term': 'Shock'}], 'ancestors': [{'id': 'D018805', 'term': 'Sepsis'}, {'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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077585', 'term': 'Terlipressin'}], 'ancestors': [{'id': 'D008236', 'term': 'Lypressin'}, {'id': 'D014667', 'term': 'Vasopressins'}, {'id': 'D010909', 'term': 'Pituitary Hormones, Posterior'}, {'id': 'D010907', 'term': 'Pituitary Hormones'}, {'id': 'D036361', 'term': 'Peptide Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D009479', 'term': 'Neuropeptides'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D009842', 'term': 'Oligopeptides'}, {'id': 'D009419', 'term': 'Nerve Tissue Proteins'}, {'id': 'D011506', 'term': 'Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Performed a randomization table before enrollment. Prepare the study drug receiving or placebo receiving according to sequential number derived from the randomization table and keep it in a conceal envelop. Prepare study drug and placebo by a pharmacist or an investigation nurse, according to the randomization table number, and keep both study drug and placebo in the identical containment which labeled by a sequential number. Once a patient was enrolled and informed was signed, then study drug or placebo was start according to sequential number.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Intervention arm: Terlipressin plus Norepinephrine and/or Epinephrine Controlled arm: Placebo plus Norepinephrine and/or Epinephrine for Treatment Refractory Septic Shock'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 130}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-04-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-09', 'completionDateStruct': {'date': '2025-07-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2021-09-23', 'studyFirstSubmitDate': '2020-04-07', 'studyFirstSubmitQcDate': '2020-04-07', 'lastUpdatePostDateStruct': {'date': '2021-09-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-04-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-03-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Achieve target blood pressure with low dose adrenergic agents', 'timeFrame': '6 hours after initiate study drug', 'description': 'Achieve target mean arterial blood pressure 65 millimeter mercury or more with norepinephrine and/or epinephrine dose 0.2 mcg/kg/min or lower'}], 'secondaryOutcomes': [{'measure': '28 day mortality', 'timeFrame': '28 days', 'description': 'Proportion of patient who dead before 28 days after enrollment'}, {'measure': 'Mean arterial blood pressure', 'timeFrame': '72 hours', 'description': 'Mean arterial blood pressure after initiate study drug'}, {'measure': 'Hospital mortality', 'timeFrame': '90 days', 'description': 'Proportion of patient who dead before hospital discharge after enrollment'}, {'measure': 'ICU mortality', 'timeFrame': '90 days', 'description': 'Proportion of patient who dead before ICU discharge after enrollment'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Septic Shock', 'Refractory Shock', 'Norepinephrine Adverse Reaction']}, 'referencesModule': {'references': [{'pmid': '28101605', 'type': 'RESULT', 'citation': 'Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.'}, {'pmid': '26903338', 'type': 'RESULT', 'citation': 'Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.'}, {'pmid': '30704260', 'type': 'RESULT', 'citation': 'Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1097-1105. doi: 10.1164/rccm.201806-1034OC.'}]}, 'descriptionModule': {'briefSummary': 'Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.\n\nFor the patient who did not response to high dose norepinephrine, epinephrine was recommended.\n\nVasopressin was also recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.\n\nTerlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.\n\nTo use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.', 'detailedDescription': 'Norepinephrine was recommended as the first vasopressor for septic shock resuscitation.\n\nFor the patient who did not response to high dose norepinephrine, epinephrine was recommended.\n\nBoth norepinephrine and epinephrine action via the alpha adrenergic stimuli to increase vascular smooth muscle contraction, induced vasoconstriction and increase arterial blood pressure. It also action via beta adrenergic stimuli, to increase heart rate and myocardial contractility, then increase stroke volume and cardiac output.\n\nToo much alpha and beta adrenergic stimulation, especially during received high dose norepinephrine and or epinephrine associated with vasoconstriction induce organs ischemia.\n\nThe most common organ ischemia included myocardial ischemia, bowel ischemia and limbs ischemia.\n\nCardiac arrhythmia was also the most common complication associated with high dose norepinephrine and or epinephrine.\n\nAtrial fibrillation was the most common reported arrhythmia, however, fatal arrhythmia included ventricular fibrillation and tachycardia were also reported.\n\nVasopressin was recommended as an alternative vasopressor, in case patient did not response to norepinephrine and or epinephrine.\n\nTerlipressin, a selective V1 receptor binding with long half life, was reported that it main action is to increase blood pressure via the different mechanism from norepinephrine and epinephrine.\n\nTo use terlipressin, combine with norepinephrine and or epinephrine among refractory septic shock, could decrease the usage dose of norepinephrine and epinephrine as well as lower the side effects of too high adrenergic stimuli.\n\nThe benefit effect of terlipressin could be demonstrated when prescribe among the septic shock patients who required high dose of adrenergic vasoactive agents.\n\nTerlipressin plus norepinephrine and or epinephrine could maintain or even improve blood pressure and tissue perfusion with lower fatal side effects than norepinephrine and or epinephrine without terlipressin.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Septic shock according to Sepsis-3 definition\n* Evidence of adequate fluid\n* Received norepinephrine 0.2 mcg/kg/min or more\n* Received norepinephrine plus epinephrine (any dose)\n* Mean arterial lower than 65 mmHg or lactate \\> 2 mmol/liter\n\nExclusion Criteria:\n\n1. Septic shock diagnosis \\> 48 hours before\n2. Receive intravenous fluid \\< 30 mL/kg before enrollment\n3. Do-not-resuscitation and terminally ill\n4. Refractory to treatment malignancy\n5. Pregnancy\n\n7\\. Chronic renal failure stage 5 with no plan for long term renal replacement therapy 8. Cirrhosis child C 9. Cardiogenic shock 10. Acute decompensated heart failure 11. Evidence of left ventricular ejection fraction (LVEF) \\< 35% 12. Acute coronary syndrome within 72 hours 13. Severe valvular heart disease 14. Documented life-threatening tachyarrhythmia before enrollment 15. Diagnosis of acute mesenteric ischemia before enrollment 16. Previous diagnosis of Raynaud's phenomenon 17. Known peripheral arterial disease 18. Refuse to sign the informed consent by patient or representative"}, 'identificationModule': {'nctId': 'NCT04339868', 'acronym': 'TERESEP', 'briefTitle': 'Terlipressin for Refractory Septic Shock', 'organization': {'class': 'OTHER', 'fullName': 'Mahidol University'}, 'officialTitle': 'Terlipressin Versus Placebo for Septic Shock Refractory to High Doses Catecholamine Vasopressors: A Randomized-controlled Trial', 'orgStudyIdInfo': {'id': 'Si 049/2020'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Terlipressin group', 'description': 'Terlipressin acetate 1 mg in 0.9% normal saline (NaCl) 50 mL (0.02 mg/mL) Initial dose 20 mcg/hr (1 mL/hr) titrate increase 1 mL/hr every 30 min to 100 mcg/hr (5 mg/hr) to keep mean arterial blood pressure (MAP) \\> 65 mmHg If MAP \\> 75 mmHg for \\> 30 min, decrease epinephrine and norepinephrine until \\< 0.15 mcg/kg/min, then decrease terlipressin until stop', 'interventionNames': ['Drug: Terlipressin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo group', 'description': 'Placebo 0.9% NaCl 50 mL Initial dose 1 mL/hr titrate increase 1 mL/hr every 30 min to 5 mg/hr to keep mean arterial blood pressure (MAP) \\> 65 mmHg If MAP \\> 75 mmHg for \\> 30 min, decrease epinephrine and norepinephrine until \\< 0.15 mcg/kg/min, then decrease placebo until stop', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Terlipressin', 'type': 'DRUG', 'description': 'Terlipressin (20-100 mcg/hr) plus norepinephrine and/or epinephrine', 'armGroupLabels': ['Terlipressin group']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '0.9% NaCl plus norepinephrine and/or epinephrine', 'armGroupLabels': ['Placebo group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10700', 'city': 'Bangkok', 'status': 'RECRUITING', 'country': 'Thailand', 'contacts': [{'name': 'Surat Tongyoo, MD', 'role': 'CONTACT', 'email': 'surat.ton@mahidol.ac.th', 'phone': '6624198534'}, {'name': 'Chawanee Chayakul, MD', 'role': 'CONTACT', 'email': 'jingjaring@gmail.com', 'phone': '080-440-1137'}, {'name': 'Tanuwong Vialasilpa, Dr', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Chawanee Chayakul, Dr', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Chairat Permpikul, Dr', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University', 'geoPoint': {'lat': 13.75398, 'lon': 100.50144}}], 'centralContacts': [{'name': 'Surat Tongyoo, MD', 'role': 'CONTACT', 'email': 'surat.ton@mahidol.ac.th', 'phone': '0820137771'}, {'name': 'Chawanee Chayakul, MD', 'role': 'CONTACT', 'email': 'jingjaring@hotmail.com', 'phone': '080-440-1137'}], 'overallOfficials': [{'name': 'Surat Tongyoo, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Mahidol University'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'CSR'], 'timeFrame': 'After complete enrollment and for 24 months', 'ipdSharing': 'YES', 'description': 'The data set and analysis are available from the corresponding author on reasonable request.', 'accessCriteria': 'Please direct contact to the principle investigator'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mahidol University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}