Clinical trial NCT04947904: OPTImized Restrictive Strategy Targeting Non-Resuscitative FLUIDs in Septic Shock: Pilot Study.
Official title: Impact on Fluid Balance of an Optimised Restrictive Strategy Targeting Non-Resuscitative Fluids in Intensive Care Patients Hospitalised for Septic Shock: an Open-label, Multi-Centre, Randomised, Controlled Pilot Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Septic Shock
Electrolyte and Fluid Balance Conditions
Keywords: Shock, Septic.
Fluid Balance
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
Collaborators: name: University Hospital, Montpellier
name: Centre Hospitalier Universitaire Dijon
First posted: 2021-07-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Intravenous fluids are one of the keystones in the initial management of patients with septic shock, but they inevitably lead to a fluid overload, which is associated with poor outcome.

So far no studies have evaluated the interest of a restrictive strategy for managing fluid intake targeting all non-resuscitative fluids (fluids for maintenance and drug dilution as well as nutrition) and especially the impact of this restrictive strategy on fluid overload.

The hypothesis of this research is that an optimised restrictive strategy targeting all non-resuscitative fluids in patients hospitalised in the intensive care unit for septic shock, will have an impact on fluid balance in these patients.

Detailed description: Sepsis and its most severe form, septic shock, are the cause of nearly 30% of admission in intensive care unit (ICU). The related mortality rate varies from 20 to 60% according to the studied population and the type of the study. With the concomitant and rapid treatment of the source of infection, hemodynamic optimization with fluid infusion (fluid resuscitation) is the cornerstone of management of patients in septic shock. Nevertheless, fluid overload has been shown to be associated with poor outcome. The negative effects of a positive fluid balance on ICU outcomes for septic patients has been well established.

In patients with acute respiratory distress syndrome, a restrictive fluid therapy has been associated with shorter use of mechanical ventilation. In patients with acute renal failure, fluid overload is associated with longer need of renal replacement therapy. In patients with septic shock numerous non-randomised studies reported that a positive fluid balance at Day 3, Day 5 was associated with an increased risk of mortality.

Actually, in patients with septic shock the part of resuscitation fluid is only the third of the total fluid input that can attain 25 liters at day 3. Some studies reported more specifically the role of the different types of fluid in the fluid balance at D3 and D5. In a retrospective single centre study including 14654 ICU patients over 10 years, the authors distinguished resuscitation, replacement and maintenance fluids, blood products, nutrition and fluid creep (to concentrate electrolytes, keep venous access and to infuse continuous medications). They reported that maintenance fluids and fluid creep represent more than 50% of fluid input during the first 5 ICU days with significant sodium and chloride loads. In a retrospective multi-centre study involving 400 patients mechanically ventilated \> 24 h in 10 ICUs, the authors reported that maintenance and fluid creep represented more than 50% of the fluids infused during the first 3 ICU days. In this study, fluid balance at Day3 was an independent risk factor for 30-day mortality.

All these findings could lead to hypothesize that a restrictive strategy in fluid input for the maintenance of fluid and creep fluid could be associated with a better outcome without impairing the resuscitation phase.

To our knowledge, to date, no study has focused on a restrictive strategy targeting non-resuscitative fluid input to optimize fluid balance in patients with septic shock. OPTIFLUID will be the first randomised controlled trial with the objective of reducing fluid balance through a fluid restriction targeted at all fluids other than resuscitative fluids.

The only existing interventional studies on targeted restriction were limited to resuscitative intravenous fluids, and they failed showing a benefit.

By optimizing fluid therapy, our approach is likely to improve patient-centred outcomes, but in this pilot study we focus only on the fluid balance and the safety.

Eligibility criteria: Inclusion Criteria:

* Patient suffering from an infection already documented or suspected
* Patient with organ dysfunction defined as an acute change in SOFA score ≥ 2 points
* Patient with refractory hypotension requiring vasopressors to maintain a mean arterial pressure ≥ 65 mm Hg in spite of resuscitation with an adequate volume of intravenous fluids (according to the recommendations of the Surviving Sepsis campaign). The treatment by vasopressor must have been started less than 24 hours before inclusion and randomization.
* Patient with hyperlactatemia (blood lactate \> 2 mmol / L). This criterion must be fulfilled at least once for the purpose of the diagnosis within the 24 hours preceding inclusion and randomization.
* Patient or close relative / legal representative / family member / curator / tutor must have given written informed consent and signed the consent form for the patient included in an emergency situation
* Patient must be covered by a health insurance scheme.
* Adult patient (≥18 years) under 85 years old (\< 85).

Exclusion Criteria:

* Patient who has had a previous episode of septic shock requiring vasopressor administration or mechanical ventilation or renal replacement therapy during the current ICU stay.
* A patient whose life expectancy is shortened due to his/her initial health condition or a moribund patient whose life expectancy is less than 48 hours or whose decision to limit comprehensive care was made before including the patient.
* Patient who has had a recent cardiac arrest (during current hospital stay)
* Patient requiring emergency renal-replacement therapy (hyperkalemia \[potassium \> 6.5 mmol/l\] refractory to medical treatment and/or metabolic acidosis \[pH \<7.15 and partial pressure of carbon dioxide (pCO2) \<45 mmHg\] refractory to medical treatment and/or pulmonary edema in anuric patients who do not respond to diuretic therapy).
* Patient with KDIGO 3 acute kidney injury and likely to require renal-replacement therapy within the next 24 hours, as determined by the patient's clinician in charge
* Patients with end-stage chronic renal failure or patients already undergoing chronic dialysis
* Severely malnourished patient in whom nutritional support is an emergency procedure (body mass index \<18 kg / m2)
* Patient participating in or having participated in an interventional study with similar patient outcome in the previous 3 months.
* Patient in an exclusion period determined by another study.
* Patient under legal protection.
* Pregnant patient (positive serum pregnancy test).

Primary outcomes:
measure: Fluid balance at day 5
timeFrame: Day 5
Secondary outcomes:
measure: Change from baseline in fluid balance at day 7
timeFrame: Day 1 to 7
measure: Change from baseline in patient's weight at day 5
timeFrame: Day 1 to 5
measure: Change from baseline in patient's weight at day 7
timeFrame: Day 1 to 7
measure: Change from baseline in central venous pressure at day 5
timeFrame: Day 1 to 5
measure: Change from baseline in central venous pressure at day 7
timeFrame: Day 1 to 7
measure: Vital status at Day 7
timeFrame: Day 7
measure: Vital status at Day 28
timeFrame: Day 28
measure: Proportion of patients alive without organ failure at Day 7
timeFrame: Day 7
measure: Proportion of patients alive without organ failure at Day 28
timeFrame: Day 28
measure: Vasopressors free days
timeFrame: Day 28
measure: Invasive mechanical ventilation free days
timeFrame: Day 28
measure: Renal-Replacement Therapy free days
timeFrame: Day 28
measure: Intensive Care Unit Length of stay
timeFrame: Day 28
measure: Intensive Care Unit Free Days
timeFrame: Day 28
measure: Hospital Length of stay
timeFrame: Day 28
measure: Frequency of metabolic disorders - moderate hypernatremia
timeFrame: Day 7
measure: Frequency of metabolic disorders - severe hypernatremia
timeFrame: Day 7
measure: Frequency of metabolic disorders - hyponatremia
timeFrame: Day 7
measure: Frequency of metabolic disorders - hyperkalemia
timeFrame: Day 7
measure: Frequency of metabolic disorders - hypoglycemia
timeFrame: Day 7
measure: Insulin cumulative dose at Day 7
timeFrame: Day 7
measure: Frequency of moderate acute kidney injury
timeFrame: Day 7
measure: Frequency of severe acute kidney injury
timeFrame: Day 7
measure: Cumulative dose of diuretics at day 7
timeFrame: Day 7
measure: Frequency of Stage 3 pressure sores
timeFrame: Day 7
measure: Daily fluid intake: Resuscitation Fluids
timeFrame: Day 1 to 7
measure: Daily fluids intake: Blood Transfusions and Blood Derivatives
timeFrame: Day 1 to 7
measure: Daily fluids intake: Maintenance Fluids
timeFrame: Day 1 to 7
measure: Daily fluids intake: Fluid Creep
timeFrame: Day 1 to 7
measure: Daily fluids intake : Enteral Nutrition
timeFrame: Day 1 to 7
measure: Daily fluids intake : Parenteral Nutrition
timeFrame: Day 1 to 7
measure: Daily fluids intake : Water
timeFrame: Day 1 to 7
measure: Daily fluids intake : intravenous fluids to treat hypernatremia
timeFrame: Day 1 to 7
Other outcomes:
Locations:
city: Alès
country: France
facility: Centre Hospitalier d'Alès
city: Dijon
country: France
facility: CHU de DIJON
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nîmes
country: France
facility: Nimes University Hospital
Study officials:
References: