Effects of Fluid Balance Control in Critically Ill Patients (POINCARE)

Effects of Fluid Balance Control in Critically Ill Patients: A Multicenter Randomized Study

Most ICU patients develop a positive fluid balance, mainly during the two first weeks of their stay. The causes are multifactorial: a reduced urine output subsequent to shock state, positive pressure mechanical ventilation, acute renal failure, post-operative period of major surgical procedures, and simultaneous fluid loading to maintain volemia and acceptable arterial pressure. Additionally, the efficacy of fluid loading is frequently suboptimal, in relation to severe hypoalbuminemia and inflammatory capillary leakage. This results usually in a cumulated positive fluid balance of more than 10 litres at the end of the first week of stay. A high number of studies have showed that such a positive fluid balance was an independent factor of worse prognosis in selected populations of ICU patients: acute renal failure, acute respiratory distress syndrome (ARDS), sepsis, post-operative of high risk surgery. However, little is known about the putative causal role of positive fluid balance by itself on outcome. However, in two randomized controlled studies in patients with ARDS, a strategy of fluid balance control has been demonstrated to reduce time under mechanical ventilation and ICU length of stay with no noticeable adverse effects. Although avoiding fluid overload is now recommended in ARDS management, there is no evidence that this approach would be beneficial in a more general population of ICU patients (i.e. with sepsis, acute renal failure, mechanical ventilation). In addition, fluid restriction -mainly if applied early could be deleterious in reducing both tissue oxygen delivery and perfusion pressure. There is a place for a prospective study comparing a "conventional" attitude based on liberal fluid management throughout the ICU stay with a restrictive approach aiming at controlling fluid balance, at least as soon as the patient circulatory status is stabilized. The latter approach would use a simple algorithm using fluid restriction and diuretics based on daily weighing, a common procedure in the ICU, probably more reliable than cumulative measurement of fluid movements in patients whose limits have been underlined.

Study Overview

• Status: Completed
• Conditions: Critical Care; Fluid Shifts
• Intervention / Treatment: Drug: diuretics; Drug: albumin; Other: fluid restriction; Device: renal replacement

• Study Type: Interventional
• Enrollment (Actual): 1411
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Belfort, France, 90000
    • Hôpital Nord Franche-Comté
  • Dijon, France, 21000
    • Centre Hospitalier Universitaire
  • Lyon, France, 69000
    • Centre Hospitalier Universitaire
  • Metz, France, 57000
    • Centre Hospitalier Regional
  • Nancy, France, 54000
    • Centre Hospitalier Regional Et Universitaire
  • Paris, France, 75000
    • Groupe Hospitalier Saint Joseph
  • Poissy, France, 78303
    • Centre Hospitalier Intercommunal
  • Strasbourg, France, 67000
    • Centre Hospitalier Regional Et Universitaire
  • Strasbourg, France, 67000
    • CentreHospitalier Régional et universitaire
  • Thionville, France, 57000
    • Centre Hospitalier Regional
  • Verdun, France, 55100
    • Centre Hospitalier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients under mechanical ventilation, admitted for > 48h and <72h and no discharge planned for the next 24h

Exclusion Criteria:

• Age < 18 years
• Failure to weigh the patient
• Multiple trauma
• Transfer from another ICU with a previous stay > 24h
• High probability of withdrawing treatment for ethical purposes within 7 days
• Pregnancy
• Patient refusal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Usual care provided according to the ward policy. Patients have to be weighed at least on admission (day 0), day 7 and day 14.
Experimental: Strategy; Patients have to be weighed every day. Use of an algorithm based on weight changes from day 2 to day 14 in order to reduce weight gain (fluid overload) using diuretics, fluid restriction,albumin, and ultrafiltration (the latter when ongoing renal replacement)	Drug: diuretics; Used to reduce fluid overload as evidenced by weight gain; Other Names: furosemide; hydrochlorothiazide; bumetanide; Drug: albumin; Used to reduce fluid overload in addition with diuretics in hypoalbuminemic patients; Other: fluid restriction; Used to reduce fluid overload; Device: renal replacement; Used to reduce fluid overload in patients with renal replacement; Other Names: ultrafiltration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality at 60 days after inclusion	Vital status collected 60 days after admission; if the patient was dead at the time of assessment, date of death was collected	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluid balance control at day 7	Mean differences of patient body weight between Day 7 and admission (Day 0)	7 days
Fluid balance control at day 14	Mean differences of patient body weight between Day 14 and admission (Day 0)	14 days
All-cause mortality at 28-day after inclusion	Vital status collected 28 days after admission	28 days
All-cause in-hospital mortality	Death during the hospital stay where the patient was included in the study	Up to 24 weeks
All-cause mortality at 365 days after inclusion	Vital status collected one year after admission	365 days
Survival time period at Day 60	Time-related mortality, calculated from admission to the date of death	60 days
Survival time period at Day 365	Time-related mortality, calculated from admission to the date of death	365 days
Global end-organ damage assessment	Time-related changes of Sequential Organ Failure Assessment (SOFA score): SOFA is a score of organ failure with 6 subscales on organ dysfunction: respiratory, neurological, cardiovascular,hepatic,renal and coagulation. Each ranges from 0 to 4 and the total SOFA score is the sum of each subscale ; increasing severity from 0 (normal) to 24(moribund). Values of SOFA score are tightly correlated with mortality.	28 days
Dependence on vasopressor drugs	Cumulated number of vasopressor-free days alive from day 0 to day 28	28 days
Dependence on mechanical ventilation	Cumulated number of ventilator-free days alive from day 0 to day 28	28 days
Dependence on renal replacement therapy	Cumulated number of renal replacement-free days alive from day 0 to day 60	60 days
Cumulated number of pre-defined adverse events	Pre-defined adverse events include Systolic arterial pressure< 90 mm Hg, kalemia < 2,8 ,mmol/L, natremia >155 mmol/L, "injury" level of renal dysfunction (RIFLE scale), acute ischemic events (myocardial infarction, mesenteric ischemia)	14 days

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Collaborators: Ministry of Health, France
• Investigators: Study Director: El Mehdi SIAGHY, Central Hospital, Nancy, France

Publications and helpful links

General Publications

• Agrinier N, Monnier A, Argaud L, Bemer M, Virion JM, Alleyrat C, Charpentier C, Ziegler L, Louis G, Bruel C, Jamme M, Quenot JP, Badie J, Schneider F, Bollaert PE. Effect of fluid balance control in critically ill patients: Design of the stepped wedge trial POINCARE-2. Contemp Clin Trials. 2019 Aug;83:109-116. doi: 10.1016/j.cct.2019.06.020. Epub 2019 Jun 29.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): May 25, 2020

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: May 5, 2016
• First Posted (Estimate): May 6, 2016

Study Record Updates

• Last Update Posted (Actual): September 22, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Diuretics; Fluid overload; Fluid restriction; Body weight; Multiple organ failure
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Hydrochlorothiazide; Furosemide; Diuretics; Bumetanide
• Other Study ID Numbers: 2015-A00662-47

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No