Clinical Trial: Early Goal Directed Therapy Using a Physiological Holistic View. The ANDROMEDA-SHOCK Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Early Goal Directed Therapy Using a Physiological Holistic View. A Multicenter Study in Latin America: The ANDROMEDA-SHOCK Study

Brief Summary:

Septic shock is a highly lethal condition associated with a mortality risk of 30 to 60%. Optimizing tissue perfusion and oxygenation is the aim to decrease mortality and morbidity in septic shock patients.

Persistent hyperlactatemia after initial resuscitation is particularly difficult to interpret, although optimizing systemic blood flow might reverse ongoing hypoperfusion. Nevertheless, if persistent hyperlactatemia is caused by non-hypoperfusion-related mechanisms, then sustained efforts aimed at increasing cardiac output (CO) could lead to detrimental effects of excessive fluids or inotropes. Another potential alternative resuscitation target is peripheral perfusion as assessed by capillary refill time (CRT), mottling score or central-to-toe temperature differences. Reversal of abnormal peripheral perfusion might represent improvement in tissue hypoperfusion with the advantage of a faster recovery than lactate.

Hypothesis: Peripheral perfusion guided resuscitation in septic shock is associated with lower mortality, less organ dysfunctions, less mechanical ventilation (MV), less vasopressor load, and less renal replacement therapies than a lactate-targeted resuscitation strategy.

Main Objective To test if peripheral perfusion targeted resuscitation in septic shock is associated with lower 28-day mortality than a lactate targeted resuscitation.

Design: Multicenter, Parallel Assignment randomized controlled study, conducted under supervision of an independent Data Safety Monitoring Board (DSMB).

Interventions:

1. Active Comparator- Peripheral Perfusion guided resuscitation
2. Early Goal Directed Therapy using a Physiological Holistic View. A multicenter study in Latin America: The ANDROMEDA-SHOCK Study

   Hypothesis Peripheral perfusion guided resuscitation in septic shock is associated with lower mortality, less organ dysfunctions, less mechanical ventilation (MV), less vasopressor load, and less renal replacement therapies than a lactate-targeted resuscitation strategy.

   Using a holistic view of optimizing tissue perfusion and oxygenation the investigators aim to decrease mortality and morbidity in septic shock patients.

   A. Background Septic shock is a highly lethal condition associated with a mortality risk of 30 to 60%. It is currently the most frequent cause of death in the intensive care unit (ICU) as the investigators demonstrated in a recent Chilean prevalence study. Several pathogenic factors such as hypovolemia, myocardial depression, vasoplegia, and microcirculatory abnormalities can induce progressive tissue hypoperfusion in severe cases. In this context, persistent hyperlactatemia has been traditionally considered as the hallmark of ongoing tissue hypoxia during septic shock, and therefore lactate normalization is recommended as a resuscitation target by the Surviving Sepsis Campaign (SSC).

   Pathophysiologic determinants of persistent hyperlactatemia

   The physiologic basis of lactate generation or clearance during septic shock has been matter of active research. Hypovolemia-induced hypoperfusion is probably the predominant pathogenic mechanism during the early phase. Some patients resolve acute circulatory dysfunction and clear lactate after initial fluid resuscitation, while others evolve into a persistent circulatory dysfunction with hype
   Sponsor: Pontificia Universidad Catolica de Chile
   

   Current Primary Outcome: All-cause of mortality [ Time Frame: 28 days ]

   All cause of mortality.
   
   
   

   Original Primary Outcome: Same as current
   
   

   Current Secondary Outcome:

   • Need of mechanical ventilation [ Time Frame: 28 days ]
     Requirement of mechanical ventilation
   • Need of renal replacement therapies (RRT) [ Time Frame: 28 days ]
     Requirement of renal replacement therapie
   • Days free of MV, vasopressors and RRT [ Time Frame: 28 days ]
     Difference between hospital length of stay and days on which the patients receive MV, vasopressors and RRT
   • Variations in Sequential Organ failure Assessment (SOFA) [ Time Frame: At 8, 24, 48 and 72 hours ]
     Differences in SOFA score between baseline and different time-points.
   
   
   

   Original Secondary Outcome: Same as current
   
   Information By: Pontificia Universidad Catolica de Chile
   

   Dates:
   Date Received: March 6, 2017
   Date Started: March 1, 2017
   Date Completion: June 1, 2018
   Last Updated: March 13, 2017
   Last Verified: March 2017