Study of Multistep Pharmacological and Invasive Management for Cardiogenic Shock

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy and safety of i.v. adrenaline infusion as an early and fast haemodynamic stabilizer, associated with a tight tissue perfusion monitoring, in the context of a stepwise progression in the treatment of cardiogenic shock, including ventricular mechanical support.

Detailed Description
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Cardiogenic shock is characterized by a decrease in cardiac output and increased ventricular pressures, with subsequent symptoms and signs of systemic hypoperfusion. In spite of the multiple pharmacological chances the in-hospital mortality rate is still very high (around 60% of patients) and nowadays there is not a therapeutic reference standard associated with an improved survival at short and midterm. Adrenaline is a mainstay of resuscitation therapy during cardiopulmonary arrest, however, it is not clear whether this inotrope actually facilitates an improvement in patients affected by cardiogenic shock. In a small local evidence-based experience, contrary to current opinion, it has been shown that adrenaline may still have a role in the treatment of patients with low output state. This phase II study tests the hypothesis that adrenaline infusion, integrated in a multistep approach at increasing intensity, can be a valid support with limited side effects.

Official Title
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Phase II Clinical Trial for a Stepwise Progression in the Treatment of Cardiogenic Shock

Conditions
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Cardiogenic Shock

Intervention / Treatment
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* Drug: adrenaline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age ≥ 18 and < 75, men and women; 1) SBP < 90mmHg or MAP < 60 mmHg, after an appropriate fluid challenge if there is no sign of overt fluid overload; OR 2) need of vasoactive agents to maintain SBP > 90 mmHg or MAP > 60 mmHg. Pre-existing diagnosis of heart failure with reduced ejection fraction (left ventricle systolic function ≤35%). Moreover, eligible patients have to fit at least ONE of the following criteria/items of overt hypoperfusion: mixed venous oxygen saturation < 60%; arterial lactates > 2 mmol/L; oliguria < 0.5 ml/Kg/h for at least 6 hours. Eligible patients shouldn't have contraindications to HRT. Exclusion Criteria Cardiogenic shock symptoms beyond 6 hours. Septic shock with evident septic focus. Cardiogenic shock due to acute myocardial infarction. Cardiogenic shock due to acute myocarditis. Cardiogenic shock due to pulmonary thromboembolism. Reiterating major arrhythmias: VT or VF or AF, with ventricular rate > 160 bpm. Severe aortic valve disease. Obstructive hypertrophic cardiomyopathy or constrictive pericarditis or severe heart failure due to congenital heart disease Severe peripheral vascular disease that contraindicates mechanical support insertion. Cardiogenic shock secondary to either cardiac or non-cardiac surgery. Post-cardiac arrest syndrome following out of hospital cardiac arrest Comorbidities with ominous prognosis (life expectancy < 1 year). End-stage organ failure. Pregnant, lactating or subjects planning pregnancy during the course of the trial. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: adrenaline<br>i.v. adrenaline infusion as an early and fast haemodynamic stabilizer, associated with a tight tissue perfusion monitoring, in the context of a stepwise progression in the treatment of cardiogenic shock, including ventricular mechanical support | Drug: adrenaline<br>* i.v. adrenaline infusion as an early and fast haemodynamic stabilizer, associated with a tight tissue perfusion monitoring, in the context of a stepwise progression in the treatment of cardiogenic shock, including ventricular mechanical support<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 60 days | number of successes | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of i.v. infusion with adrenaline |  | 30 days | 
| Adrenaline maximum dose |  | 30 days | 
| Time to weaning from beginning with pharmacological therapy and mechanical ventricular support |  | 30 days | 
| Length of stay |  | 30 days | 
| Sum of medical staff support and nursing-care hours dedicated to each patient |  | Within patient hospitalization, each day from day 1 to day 30 | 
| Membrane oxygenation | Escalation to venoarterial extracorporeal membrane oxygenation (VA-ECMO) | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adrenaline, Extra Corporeal Life Support, Inotropes