Milrinone Versus Placebo in Patients With Septic Shock

Study Overview
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Brief Summary
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Sepsis is one of the most serious healthcare problems, worldwide, and financial burdens. The overall mortality of severe sepsis/septic shock was 44.5-52.6%. A common cause of death is refractory shock and multi-organ failure. Myocardial dysfunction is a relatively common complication of septic shock. This causes a decrease in the amount of cardiac output, resulting in insufficient blood supply to the organ and multi-organ failure and lead to death Early goal-directed therapy began to use dobutamine in patients with septic shock Sepsis Survival Campaign Guideline 2016 recommended drug is dobutamine and an alternative drug is milrinone in septic shock patients with clinical signs of poor tissue perfusion.

Detailed Description
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According to several studies, the use of dobutamine increases the amount of cardiac output but it has also been reported to increase mortality rates too. There are few studies of milrinone in patients with septic shock.

Official Title
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Effect of Milrinone Versus Placebo on Hemodynamics in Patients With Septic Shock; Randomized Control Trial

Conditions
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Septic Shock, Cardiac Output

Intervention / Treatment
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* Drug: Milrinone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years old Diagnosis Septic Shock from the definition of SEPSIS III in intensive care unit at Siriraj hospital and Hat-Yai hospital Receive fluid resuscitation at least 30 ml/kg and/or Vasopressor until mean arterial pressure ≥ 65 mmHg Persistence lactate >2mmol/L at 6th hour after resuscitation Urine output < 0.5 ml/kg at 6th hour after resuscitation Left ventricular ejection fraction (LVEF) < 40 % Exclusion Criteria: Chronic kidney disease stage 5 and denied renal replacement therapy Life-threatening tachyarrhythmia before enrolled e.g. Ventricular tachycardia, Ventricular fibrillation Patient sign do-not-resuscitation and terminally ill

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Milrinone group<br>The pharmacist prepares milrinone 20 mg with normal saline solution (NSS) 100 ml then starts dose 0.5 mg/kg/min for up to 12 hours. The doctor performs Echocardiogram before start Milrinone, during infusion, and after 12 hours from stop Milrinone. Other medications or interventions were used or not used depending on own doctor. | Drug: Milrinone<br>* Prepare milrinone 20 mg with NSS 100 ml then starts dose 0.5 mg/kg/min for up to 12 hours.<br>* Other names: Primacor;|
| Placebo Comparator: Placebo group<br>The pharmacist uses 100 ml of NSS, packed out in the same format, dose, and administration of the drug were exactly the same as in the milrinone group. The doctor performs Echocardiogram same time as the milrinone group | Drug: Milrinone<br>* Prepare milrinone 20 mg with NSS 100 ml then starts dose 0.5 mg/kg/min for up to 12 hours.<br>* Other names: Primacor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of cardiac output from baseline (before study drug administration) to 6 hours (during study administration) | by echocardiogram or Pulse contour analysis or Thermodilution technique from pulmonary artery catheter | upto 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensive care unit (ICU) mortality | Proportion of participant who die during ICU admission | upto 120 days | 
| Hospital mortality | Proportion of participant who die during hospital admission | upto 120 days | 
| 28-day mortality | Proportion of participant who die during 28 days after enrollment | upto 28 days | 
| Dose of vasopressor after intervention | present as vasopressor equivalent dose compare before and after intervention, and percent of decrease | upto 7 days | 
| Lactate clearance | lactate level after and before intervention and percent clearance | upto 7 days | 
| Mechanical ventilator free day | day of the patient does not use mechanical ventilator during admission | upto 28 days | 
| Extracorporeal membrane oxygenation (ECMO) or Renal replacement therapy (RRT) | incident of initial ECMO or RRT | upto 28 days | 
| Incident of tachyarrhythmia | Incident of ventricular tachycardia, ventricular fibrillation, Atrial fibrillation | upto 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Milrinone, Septic shock, Cardiac output, Poor tissue perfusion