Use of Dobutamine in Patients With Sepsis and Maintained Hypoperfusion After Initial Volemic Resuscitation.

Study Overview
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Brief Summary
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This phase 2 study aim to investigate the effect of dobutamine in patients with sepsis/ septic shock after fluid resuscitation and with hypoperfusion (lactate and central venous oxygen saturation or prolonged capillary refill time) on renal function as compared with usual care.

Detailed Description
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In this phase 2 study patients with sepsis/ septic shock and signs of persistent hypoperfusion after fluid resuscitation will be randomized to receive either dobutamine or no intervention in addition to usual care. Dobutamine will be used for 48 hours. Hypoperfusion will be assessed by altered lactate levels and a low SvO2 or prolonged capillary refill time. Both arms will receive usual care according to the Surviving Sepsis Campaign guidelines. Dobutamine dosis will be adjusted to achieve improvement in the perfusion parameters according to a pre specified protocol. Pre specified criteria will be used to stop the drug for safety. The primary outcome will be creatinine at Day 3. Other secondary and safety outcomes will also be assessed.

Official Title
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Use of Dobutamine in Patients With Sepsis and Maintained Hypoperfusion After Initial Volemic Resuscitation.

Conditions
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Sepsis, Hypoperfusion, Hyperlactatemia

Intervention / Treatment
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* Drug: Dobutamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years old Patient with sepsis (suspected or confirmed) for less than 48 hours with: Adequate volume resuscitation with 30 ml/kg of crystalloid solution or assessment by the attending physician that fluid resuscitation is no longer indicated Signs of hypoperfusion for less than 12 hours assessed by arterial lactate over two times the reference value and central venous saturation (SvcO2) less than 66% OR capillary refill time greater than 3 seconds. Exclusion Criteria: Pregnancy Risk of imminent death within the next 12 hours in the opinion of the attending physician Patients under end of live care Previous congestive heart failure in functional class IV and/or dependence for all basic activities of daily living Hemoglobin levels below 7.0 g/dL Current use of dobutamine Patients in renal replacement therapy

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Patients in this group will receive the usual treatment according to the Surviving Sepsis Campaign guidelines. | |
| Experimental: Dobutamine<br>Patients in this group will receive, in addition to usual care, dobutamine in continuous infusion for a period of 48 hours after the randomization. | Drug: Dobutamine<br>* Intravenous infusion of dobutamine in incremental dosis according to perfusion markers for a period of 48 hours after randomization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum creatine on the third day | Serum creatinine corrected by fluid balance on the third day | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU mortality | death in the ICU truncated at 60 days | 60 days | 
| Renal replacement therapy up to day 7 | need for renal replacement therapy within the first 7 days after randomization | 7 days | 
| Hospital mortality | death in the hospital truncated at 60 days | 60 days | 
| Vasopressors free days up to day 7 | Days without vasopressors support within the first 7days after randomization | 7 days | 
| ICU free days up to day 28th | Days out of the ICU within the first 28 days after randomization | 28 days | 
| Severe arrhythmia | Occurence of severe arrhythmia defined by the need for cardioversion (electric or chemical) | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sepsis, hypoperfusion, dobutamine