Monitoring Resuscitation in Severe Sepsis and Septic Shock

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01747057
Recruitment Status : Unknown
Verified February 2014 by Antonio Artigas Raventós, Corporacion Parc Tauli.
Recruitment status was:  Recruiting
First Posted : December 11, 2012
Last Update Posted : February 13, 2014
Information provided by (Responsible Party):
Antonio Artigas Raventós, Corporacion Parc Tauli

Brief Summary:
Our hypothesis is that hemodynamic fluid resuscitation guided by dynamic parameters will improve outcome in patients with severe sepsis and septic shock, by limiting the deleterious effects of fluid overload.

Condition or disease Intervention/treatment Phase
Hemodynamics Behavioral: Dynamic-parameters-guided fluid management Behavioral: Standard-guided-fluid management Not Applicable

Detailed Description:
To evaluate the efficacy of dynamic parameters versus static measures to guide fluid resuscitation we pretend to detect a 10% relative reduction in mortality. In addition, we pretend to observe an improvement on the length of resuscitation time, mechanical ventilation and vasopressor support-free days, ICU and hospital length of stay, organ failure and renal function.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 952 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Monitoring Resuscitation in Severe Sepsis and Septic Shock
Study Start Date : March 2013
Estimated Primary Completion Date : February 2015
Estimated Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis Shock

Arm Intervention/treatment
Experimental: Dynamic guide resuscitation
This arm follows a resuscitation protocol based on dynamic-parameters-guided fluid management.
Behavioral: Dynamic-parameters-guided fluid management

● In preload-responsive patients defined by the following dynamic parameters: Patients fully adapted to mechanical ventilation* and with sinus rhythm.

  1. PPV >12%. PPV: Pulse pressure variation PPV = (PPmax-PPmin)/ [(PPmax+PPmin)/2] x100 (during 5 respiratory cycles)
  2. SVV > 12% (15). SVV: Stroke volume variation

    • A tidal volume (Vt) ≥ 7-10cc/kg in mechanically ventilated (in a controlled mode - control volume or control pressure) and well-adapted patients without any inspiratory effort should be guaranteed.

Fluid loading must be performed with crystalloids (1omL/Kg) or colloids (5ml/Kg) every 30 minutes until PPV-SVV < 12%, while hypoperfusion signs are present. Continue resuscitation following Surviving Sepsis Campaign rules excluding more fluid administration (as described in the standard intervention once CVP>12).

● Non-preload responsive patients (defined as PPV or SVV < 12%) will resume the same protocol as responders when fluid response parameters are negative.

Active Comparator: Standard resuscitation
This arm follows a common resuscitation protocol based on Surviving Sepsis Campaign recommendations.
Behavioral: Standard-guided-fluid management
Fluid loading in patients with hypotension or elevated lactates until normalization of MAP (> 65mmHg) or CVP > 12mmHg. If CVP reaches > 12 mmHg and MAP remains < 65mmHg, norepinephrine should be started to reach MAP > 65mmHg. Once MAP is restored, if hypoperfusion signs persist (elevated lactate or urine output < 0.5mL/Kg/h), ScvO2/SvO2 must be measured. In order to reach a ScvO2 ≥70% or SVO2 ≥65%, consider giving blood transfusion if hemoglobin level (Hb) ≤ 7g/dL, and also consider dobutamine (initial dose 2,5 µg/kg/min, increased by 2,5 µg/kg/min every 30 min up to a maximum dose of 20 µg/kg/min, presence of arrhythmia, or FC>110bpm). At that point, if hypoperfusion signs remain present, consider restart protocol from the beginning.

Primary Outcome Measures :
  1. Mortality at 28 days [ Time Frame: 28 days after hospital admission ]

Secondary Outcome Measures :
  1. Length of resuscitation [ Time Frame: 72 hours after protocol inclusion ]
    • Vasopressor use and fluid load between 0h to 6h
    • Vasopressor use and fluid load between 7h to 72h

  2. Ventilator-free days [ Time Frame: 28 days after admission ]
    From 1 to 28 days over 28 days in a month.

  3. Vasopressor-free days [ Time Frame: 28 days after admission ]
    From 1 to 28 days over 28 days in a month.

  4. Organ failure-free days [ Time Frame: 28 days after admission ]
    Cardiovascular, CNS, renal, hepatic, coagulation abnormalities. From 1 to 28 days over 28 days in a month.

  5. ICU length of stay [ Time Frame: At ICU discharge (expected average 30 days after admission) ]
  6. Hospital length of stay [ Time Frame: At hospital discharge (expected average 45 days after hospital admission) ]
  7. Renal function evolution [ Time Frame: 3 days after study enrollment ]
    Creatinin clearance will be calculated every day for the first 3 days (Cockroft-Gault formula).

  8. Mortality at 3 months [ Time Frame: 3 months after admission ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age > 18 years
  • Clinical evidence of sepsis (microbiology confirmation, radiological or direct view - pus in biological fluid or surgical direct view-).
  • ≥ 2 SIRS criteria:

    • Temperature < 36.0°C or > 38.0°C
    • Heart rate > 90 bpm
    • Respiratory rate > 20 rpm or PaCO2 < 32 mmHg or need of mechanical ventilation.
    • Leukocytes > 12.0 x109/L or < 4.0 x109/L
  • Hemodynamic insufficiency defined as (at least one of the following):

    • Sustained systemic hypotension (systolic arterial pressure ≤ 90 mmHg or MAP < 65 mmHg) or a decrease in MAP of > 30 mm Hg in a hypertensive patient.
    • Need of vasopressors.
    • Tachycardia (HR > 110 bpm) or bradycardia (HR < 55 bpm)
    • Acute onset of oliguria, defined as a decreased urine output < 0.5 ml/kg/hr for ≥ 2 hours
    • Serum lactate > 2 mmol/l
    • Peripheral cyanosis, mottled skin, prolonged capillary refill
  • Mechanical ventilation without any kind of inspiratory effort and Vt 7-10 mL/Kg, Pplateau < 30 mmH2O. Those patients with ARDS under mechanical ventilation will need to tolerate a tidal volume of at least 7 mL/Kg during 30 seconds while the plateau pressure remains < 30 mmH2O.
  • Prior hemodynamic monitoring by arterial catheter.
  • Central venous catheter.

Exclusion Criteria:

  • Acute myocardial infarction < 7 days.
  • Pregnancy
  • Prior request of limited code status or expected life length lower than 3 months.
  • Shock > 12h
  • Cardiac arrhythmia
  • Aortic valvular disease
  • Inability to properly measure arterial pressure wave forms

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01747057

Contact: Xaime Garcia, MD +34937231010 ext 21156
Contact: Gisela Gili, RN +34937231010 ext 21159

Area de Critics. Hospital de Sabadell Recruiting
Sabadell, Barcelona, Spain, 08208
Contact: Gemma Goma, RN    937231010 ext 21179   
Principal Investigator: Xaime Garcia, MD         
Sub-Investigator: Guillem Gruartmoner, MD         
Sponsors and Collaborators
Corporacion Parc Tauli

Additional Information:
Responsible Party: Antonio Artigas Raventós, Director of Critical Care Area, Corporacion Parc Tauli Identifier: NCT01747057     History of Changes
Other Study ID Numbers: MORESS
First Posted: December 11, 2012    Key Record Dates
Last Update Posted: February 13, 2014
Last Verified: February 2014

Additional relevant MeSH terms:
Shock, Septic
Systemic Inflammatory Response Syndrome
Pathologic Processes