Overview
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.
Description
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.
Eligibility
Inclusion Criteria: 1\&2
- Age ≥ 19
- Cardiogenic shock (a) in the stage of Society for cardiovascular angiography and intervention (SCAI) C or D
- Cardiogenic shock (a) was defined as follows, and should fulfill both 1) and 2)
- systolic blood pressure \<90 mm Hg for ≥30 min or need of inotropes or vasopressors to maintain systolic blood pressure \>90 mm Hg And
- Impaired cardiac function confirmed by cardiac catheterization or echocardiography
a Cardiogenic shock was defined as follows, and should fulfill both 1) and 2)
- Cardiogenic shock (a) was defined as follows, and should fulfill both 1) and 2)
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- systolic blood pressure \<90 mm Hg for ≥30 min or need of inotropes or vasopressors to maintain systolic blood pressure \>90 mm Hg And
- Impaired cardiac function confirmed by cardiac catheterization or echocardiography
- Cardiac index (CI) \< 2.2 L/min/m², measured by pulmonary artery catheter
- Left ventricular ejection fraction LVEF \< 45% on echocardiography;
- Right ventricular dysfunction, defined by one or more of: TAPSE \< 17 mm; S' \< 9.5 cm/sec; FAC \< 35%11; or visual estimation of RV wall motion abnormality.
Or Structural cardiac abnormality capable of causing cardiogenic shock, even if LV/RV systolic indices do not meet the thresholds above (examples, infarct ventricular septal rupture or severe valvular regurgitation)
Patients will be further classified based on the SCAI shock classification system12 as follows:
- SCAI B: no signs of hypoperfusion
- SCAI C: any signs of hypoperfusion, cardiogenic shock will be classified as SCAI C, and these include mental status change, cool and clammy skin, mottled skin appearance, decreased urine output (30ml/hour) or lactate over 2.0mmol/L
- SCAI D: shock progression despite use of the index vasoactive agent at ≥75% of the predefined maximal dose
- SCAI E: Impending arrest or overt circulatory collapse
Exclusion Criteria: any of these,
- Administration of vasoactive drug more than 6 hours before enrollment
- Receiving norepinephrine or dopamine at doses exceeding the protocol defined maximal dose at the time of enrollment.
- Receiving any vasoactive agent other than norepinephrine or dopamine
- Patients receiving a continuous infusion of both norepinephrine and dopamine
- Patients already on temporary mechanical circulatory supportb before enrollment
- Cardiogenic shock in the stage of SCAI E
- Glasgow Coma Scale lower than 8 or other evidence of irreversible brain injury
- Shock etiologies other than cardiogenic which include postcardiotomy shock or mixed shock
- Pregnancy or lactation
