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The goal of this multicenter, open-label, randomized clinical trial is to learn whether norepinephrine or dopamine is more effective and safer as the first-line vasoactive drug for treating cardiogenic shock in adults. Cardiogenic shock is a life-threatening condition in which the heart cannot pump enough blood to supply the body. The main questions this study aims to answer are:
Does norepinephrine reduce the risk of death or worsening cardiogenic shock compared with dopamine?
Does norepinephrine lead to fewer complications such as arrhythmias, the need for mechanical circulatory support, or cardiac arrest?
Researchers will compare norepinephrine and dopamine to see which drug better stabilizes blood pressure, improves tissue perfusion, and prevents progression of shock during the early phase of treatment.
Participants will:
Be randomly assigned to receive either norepinephrine or dopamine as the first vasoactive drug
Receive treatment and monitoring based on current clinical guidelines for cardiogenic shock
Undergo regular assessments of blood pressure, laboratory values, heart rhythm, and organ function during hospitalization
Be followed for outcomes at 1 month, 6 months, and 1 year after enrollment
This study aims to provide evidence that will help determine which initial vasoactive drug offers better outcomes for patients with cardiogenic shock and guide future treatment recommendations.
Cardiogenic shock is a severe form of acute circulatory failure characterized by inadequate cardiac output, tissue hypoperfusion, and high short-term mortality. Despite advances in revascularization, mechanical circulatory support, and critical care management, early hemodynamic stabilization remains a major determinant of clinical outcomes. Vasoactive drugs are essential components of initial therapy, yet the optimal first-line agent for cardiogenic shock has not been definitively established.
Norepinephrine and dopamine are widely used vasoactive agents, but they may exert their effects through different physiological mechanisms. Their relative impact on vascular tone, cardiac output, and heart rate can vary depending on dose, patient characteristics, and the underlying pathophysiology of shock. Prior studies, including observational analyses and a landmark randomized trial, have suggested potential differences in safety profiles-particularly regarding arrhythmias-but these findings have not been confirmed in a contemporary population with standardized shock definitions and modern management strategies.
This multicenter, open-label, randomized clinical trial is designed to compare norepinephrine and dopamine as the initial vasoactive drug in adults with cardiogenic shock. The study uses a protocol-defined dosing algorithm to ensure consistent titration and incorporates current guideline-based management across participating centers. The primary endpoint evaluates both early hemodynamic deterioration and 28-day mortality, reflecting clinically meaningful outcomes during the most vulnerable phase of shock.
By enrolling a large, diverse population across multiple centers, this trial aims to provide definitive evidence regarding the comparative effectiveness and safety of norepinephrine versus dopamine as first-line therapy. The results are expected to inform clinical guidelines and support standardized treatment strategies for patients with cardiogenic shock.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Norepinephrine First-Line Vasoactive Drug | Experimental | Participants assigned to this arm will receive norepinephrine as the first-line vasoactive drug for the treatment of cardiogenic shock. The drug will be initiated and titrated according to the protocol-defined dosing algorithm, with adjustments based on hemodynamic response, laboratory values, and clinical status. If participants were receiving vasoactive agents before randomization, norepinephrine will be started at an equivalent protocol-defined dose, and other agents will be tapered as clinically appropriate. All treatment and monitoring will follow current clinical guidelines for cardiogenic shock. |
|
| Dopamine First-Line Vasoactive Drug | Active Comparator | articipants assigned to this arm will receive dopamine as the first-line vasoactive drug for the treatment of cardiogenic shock. The drug will be initiated and titrated according to the protocol-defined dosing algorithm, with adjustments based on hemodynamic response, laboratory values, and clinical status. If participants were receiving vasoactive agents before randomization, dopamine will be started at an equivalent protocol-defined dose, and other agents will be tapered as clinically appropriate. All treatment and monitoring will follow current clinical guidelines for cardiogenic shock. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Norepinephrine | Drug | Norepinephrine will be administered as an intravenous continuous infusion and used as the first-line vasoactive drug for the treatment of cardiogenic shock. The medication will be prepared in standard intensive care unit infusion bags and delivered through a controlled infusion pump. The infusion will be initiated and titrated according to a protocol-defined dosing algorithm, with adjustments based on blood pressure, hemodynamic response, laboratory values, and overall clinical assessment. If a participant was receiving vasoactive agents before randomization, norepinephrine will be started at an equivalent protocol-defined dose, and non-assigned agents will be tapered as clinically appropriate. The duration of infusion will depend on the participant's clinical stabilization. All administration and monitoring will follow current clinical guidelines for cardiogenic shock. |
| Measure | Description | Time Frame |
|---|---|---|
| A composite of 28-day all-cause death or signs of progressive or refractory cardiogenic shock within the first 24 hours | signs of progressive or refractory cardiogenic shock within the first 24 hours, defined as follows, any of:
| 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause death at 28th day | 28 days | |
| Cardiovascular death at 28th day | 28 days | |
| Number of participants who develop signs of progressive or refractory cardiogenic shock within the first 24 hours |
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Inclusion Criteria: 1&2
Age ≥ 19
Cardiogenic shocka in the stage of Society for cardiovascular angiography and intervention (SCAI) C or D
Cardiogenic shock was defined as follows, and should fulfill both 1) and 2)
Patients will be further classified based on the SCAI shock classification system as follows:
Exclusion Criteria: any of these,
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Min Chul Kim, Professor, MD, PhD | Contact | 82-10-4606-2643 | kmc3242@hanmail.net | |
| Yongwhan Lim, Professor, MD | Contact | 82-10-3229-3392 | kalmiarmfl@naver.com |
| Name | Affiliation | Role |
|---|---|---|
| Min Chul Kim, Professor, MD, PhD | Chonnam National University Hospital | Principal Investigator |
| Min Chul Kin, Professor, MD, PhD | Chonnam National University Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chonnam National University Hospital | Gwangju | 61469 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34447992 | Background | McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available. | |
| 30571511 |
| Label | URL |
|---|---|
| eCRF | View source |
Not provided
ndividual participant data (IPD) will not be shared because of privacy considerations, regulatory requirements, and institutional policies governing the handling of sensitive clinical information. The study involves critically ill patients with cardiogenic shock, and sharing detailed participant-level data may pose risks to confidentiality. Only aggregated study results will be made publicly available.
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| ID | Term |
|---|---|
| D012770 | Shock, Cardiogenic |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D009638 | Norepinephrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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|
| Dopamine Agent | Drug | Dopamine will be administered as an intravenous continuous infusion and used as the first-line vasoactive drug for the treatment of cardiogenic shock. The medication will be prepared in standard intensive care unit infusion bags and delivered through a controlled infusion pump. The infusion will be initiated and titrated according to a protocol-defined dosing algorithm, with adjustments based on blood pressure, hemodynamic response, laboratory values, and overall clinical assessment. If a participant was receiving vasoactive agents before randomization, dopamine will be started at an equivalent protocol-defined dose, and non-assigned agents will be tapered as clinically appropriate. The duration of infusion will depend on the participant's clinical stabilization. All administration and monitoring will follow current clinical guidelines for cardiogenic shock. |
|
defined as follows, any of:
|
| the first 24 hours |
| Number of participants who initiate mechanical circulatory support within the first 24 hours | Impella, ECMO or IABP | the first 24 hours |
| Number of participants who initiate a second-line vasoactive drug within the first 24 hours | the first 24 hours |
| Number of participants with cardiac arrest requiring cardiopulmonary resuscitation within the first 24 hours | the first 24 hours |
| Number of participants with arrhythmia requiring electrical cardioversion within the first 24 hours | the first 24 hours |
| Number of participants who receive cardiac replacement treatment (temporary or durable mechanical circulatory support or heart transplantation) within the first 28 days | Temporary mechanical circulatory support include Impella, ECMO or IABP. | First 28 days |
| Number of participants with first-time initiation of renal replacement therapy for acute kidney injury (AKI) during initial hospitalization | First 28 days |
| Duration of vasoactive drug use (hours) during initial hospitalization | Discontinuation of vasoactive drugs is defined as the point when they are no longer required for more than 24 hours and there is no recurrence of shock. | First 28 days |
| Number of participants with new-onset or recurrent atrial or ventricular arrhythmia requiring pharmacologic or electrical cardioversion during initial hospitalization | First 28 days |
| Number of participants who develop acute limb ischemia requiring surgical or interventional treatment during initial hospitalization | First 28 days |
| Number of participants who develop ischemic or hemorrhagic stroke during initial hospitalization | First 28 days |
| All-cause death at 1 year | 1 year |
| Cardiovascular death at 1 year | 1 year |
| Number of participants with rehospitalization due to heart failure within 1 year | 1 year |
| Number of participants with first-time initiation of renal replacement therapy at 1 year | 1 year |
| Background |
| Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018 Nov 13;138(20):e618-e651. doi: 10.1161/CIR.0000000000000617. No abstract available. |
| 22890468 | Background | Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84. doi: 10.1159/000339789. Epub 2012 Aug 7. No abstract available. |
| 28183511 | Background | Lansky AJ, Messe SR, Brickman AM, Dwyer M, van der Worp HB, Lazar RM, Pietras CG, Abrams KJ, McFadden E, Petersen NH, Browndyke J, Prendergast B, Ng VG, Cutlip DE, Kapadia S, Krucoff MW, Linke A, Moy CS, Schofer J, van Es GA, Virmani R, Popma J, Parides MK, Kodali S, Bilello M, Zivadinov R, Akar J, Furie KL, Gress D, Voros S, Moses J, Greer D, Forrest JK, Holmes D, Kappetein AP, Mack M, Baumbach A. Proposed Standardized Neurological Endpoints for Cardiovascular Clinical Trials: An Academic Research Consortium Initiative. J Am Coll Cardiol. 2017 Feb 14;69(6):679-691. doi: 10.1016/j.jacc.2016.11.045. |
| 29891620 | Background | Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel MA, van Es GA, Zuckerman B, Fearon WF, Taggart D, Kappetein AP, Krucoff MW, Vranckx P, Windecker S, Cutlip D, Serruys PW; Academic Research Consortium. Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document. Circulation. 2018 Jun 12;137(24):2635-2650. doi: 10.1161/CIRCULATIONAHA.117.029289. |
| 34818495 | Background | Mathew R, Di Santo P, Hibbert B. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. Reply. N Engl J Med. 2021 Nov 25;385(22):2108-2109. doi: 10.1056/NEJMc2114890. No abstract available. |
| 36017572 | Background | Zeppenfeld K, Tfelt-Hansen J, de Riva M, Winkel BG, Behr ER, Blom NA, Charron P, Corrado D, Dagres N, de Chillou C, Eckardt L, Friede T, Haugaa KH, Hocini M, Lambiase PD, Marijon E, Merino JL, Peichl P, Priori SG, Reichlin T, Schulz-Menger J, Sticherling C, Tzeis S, Verstrael A, Volterrani M; ESC Scientific Document Group. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022 Oct 21;43(40):3997-4126. doi: 10.1093/eurheartj/ehac262. No abstract available. |
| 39210723 | Background | Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM, De Potter TJR, Dwight J, Guasti L, Hanke T, Jaarsma T, Lettino M, Lochen ML, Lumbers RT, Maesen B, Molgaard I, Rosano GMC, Sanders P, Schnabel RB, Suwalski P, Svennberg E, Tamargo J, Tica O, Traykov V, Tzeis S, Kotecha D; ESC Scientific Document Group. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024 Sep 29;45(36):3314-3414. doi: 10.1093/eurheartj/ehae176. No abstract available. |
| 37622654 | Background | Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Juni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023 Oct 12;44(38):3720-3826. doi: 10.1093/eurheartj/ehad191. No abstract available. |
| 40014670 | Background | Rao SV, O'Donoghue ML, Ruel M, Rab T, Tamis-Holland JE, Alexander JH, Baber U, Baker H, Cohen MG, Cruz-Ruiz M, Davis LL, de Lemos JA, DeWald TA, Elgendy IY, Feldman DN, Goyal A, Isiadinso I, Menon V, Morrow DA, Mukherjee D, Platz E, Promes SB, Sandner S, Sandoval Y, Schunder R, Shah B, Stopyra JP, Talbot AW, Taub PR, Williams MS. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025 Apr;151(13):e771-e862. doi: 10.1161/CIR.0000000000001309. Epub 2025 Feb 27. |
| 19794327 | Background | Gaies MG, Gurney JG, Yen AH, Napoli ML, Gajarski RJ, Ohye RG, Charpie JR, Hirsch JC. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. 2010 Mar;11(2):234-8. doi: 10.1097/PCC.0b013e3181b806fc. |
| 39130139 | Background | Naidu SS, Baran DA, Jentzer JC, Hollenberg SM, van Diepen S, Basir MB, Grines CL, Diercks DB, Hall S, Kapur NK, Kent W, Rao SV, Samsky MD, Thiele H, Truesdell AG, Henry TD. SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of Validation Studies: This statement was endorsed by the American College of Cardiology (ACC), American College of Emergency Physicians (ACEP), American Heart Association (AHA), European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC), International Society for Heart and Lung Transplantation (ISHLT), Society of Critical Care Medicine (SCCM), and Society of Thoracic Surgeons (STS) in December 2021. J Soc Cardiovasc Angiogr Interv. 2022 Jan 30;1(1):100008. doi: 10.1016/j.jscai.2021.100008. eCollection 2022 Jan-Feb. No abstract available. |
| 36327286 | Background | Na SJ, Yang JH, Ko RE, Chung CR, Cho YH, Choi KH, Kim D, Park TK, Lee JM, Song YB, Choi JO, Hahn JY, Choi SH, Gwon HC. Dopamine versus norepinephrine as the first-line vasopressor in the treatment of cardiogenic shock. PLoS One. 2022 Nov 3;17(11):e0277087. doi: 10.1371/journal.pone.0277087. eCollection 2022. |
| 20200382 | Background | De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL; SOAP II Investigators. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010 Mar 4;362(9):779-89. doi: 10.1056/NEJMoa0907118. |
| 40100174 | Background | Sinha SS, Morrow DA, Kapur NK, Kataria R, Roswell RO. 2025 Concise Clinical Guidance: An ACC Expert Consensus Statement on the Evaluation and Management of Cardiogenic Shock: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2025 Apr 29;85(16):1618-1641. doi: 10.1016/j.jacc.2025.02.018. Epub 2025 Mar 17. No abstract available. |
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| 38855925 | Background | Choi KH, Kang D, Park H, Park TK, Lee JM, Song YB, Hahn JY, Choi SH, Gwon HC, Cho J, Yang JH. In-hospital and long-term outcomes of cardiogenic shock complicating myocardial infarction versus heart failure. Eur J Heart Fail. 2024 Jul;26(7):1594-1603. doi: 10.1002/ejhf.3333. Epub 2024 Jun 10. |
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| D014652 |
| Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
| D012769 | Shock |
| D000588 |
| Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |