RApid Fluid Volume EXpansion in Patients in Shock After the Initial Phase of Resuscitation. (RAVEXO)

February 13, 2025 updated by: Centre Hospitalier Régional d'Orléans

RApid Fluid Volume EXpansion (RVE) in Critically Ill Patients With Acute Circulatory Failure After the Initial Phase of Resuscitation. A Single-center, Open-label, Randomized Study Comparing 3 Strategies of RVE in Orléans, France.

Rapid volume expansion using repeated intravenous fluid boluses is a very common intervention performed in the intensive care unit (ICU) in the early days of resuscitation of patients with shock. Once passed the initial phase of resuscitation, the fluid boluses administered fail to effectively increase the patients' cardiac output in about 50% of cases. Pulse pressure changes or stroke volume changes induced by a Passive Leg Raising (PLR) test have acceptable/good ability to predict fluid responsiveness (in terms of cardiac output change) and may be systematically used in patients with persistent shock with the aim of limiting the total amount of fluid administered to patients by avoiding undue fluid boluses. One may suppose that such a volume expansion management policy could impact morbidity and mortality of shocked patients. Among the predictive indices available in clinical practice, the PLR test has the advantages of being usable regardless of the patients' respiratory status and cardiac rhythm. Changes in left ventricular stroke volume during the PLR test perform better that changes in pulse pressure to predict fluid responsiveness. However, in counterpart, pulse pressure changes during PLR can be assessed without the need of other hemodynamic exploration such central venous pressure measurement or cardiac output monitoring. The investigators hypothesized that strategies using either stroke volume changes or pulse pressure changes induced by the PLR test to decide wether a fluid bolus clinically deemed indicated should or should not be administered, may limit the amount of fluid received by the patients during the first 5 days of shock, improve their oxygenation index, and shorten the time passed under mechanical ventilation, as compared to a "liberal" strategy (usual care) that does not use predictive indices of fluid responsiveness.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

A pilot, single-center, randomized, open-label, 3 parallel groups clinical trial with 1:1:1 assignment of interventions, comparing outcomes between patients with persistent shock assigned to either 1) the "Volume expansion guided by PLR-induced changes in Stroke Volume" strategy, or 2) the "Volume expansion guided by PLR-induced changes in Pulse Pressure" strategy, or 3) to usual care (i.e., without the use of any predictive index of fluid responsiveness). Patients in shock (either of septic, cardiac or other origin) will be included once passed the first hours of resuscitation. The time window for inclusion will be from 6 to 24 hours after the beginning of resuscitation, a delay necessary to ensure that initial hypovolemia has been fully compensated.

The randomization will be stratified according to the presumed origin of shock (cardiac, septic, or other) and according to the PaO2/FiO2 ratio (<200 or ≥ 200 mmHg).

The randomly assigned intervention will be used during the first 5 days of shock (120 hours).

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Orléans, France, 45000
        • Centre Hospitalier Régional d'Orléans, France

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Pre-eligibility criteria:

  • Patients presenting on Intensive Care Unit (ICU) admission or later during their ICU stay with arterial hypotension (Mean arterial pressure [MAP]<65mmHg or systolic arterial pressure [SAP]< 90 mmHg at least two times over a 15-minute interval), regardless of the method used to measure blood pressure (invasive or non invasive),
  • Or patients already receiving continuous iv vasopressor therapy on ICU admission, regardless of the blood pressure level, will be considered as potential candidates for inclusion in the study, depending on his/her clinical evolution after 6 to 24 hours of care according to current guidelines for shock management.
  • In case arterial hypotension is present and/or the patient is already receiving continuous iv vasopressor at ICU admission, the date and time of admission will be considered as the time of shock onset (H0).
  • In case arterial hypotension occurs after ICU admission, the date and time of the first episode of hypotension will be considered as the time of shock onset (H0).

Inclusion Criteria:

  • Patients will be eligible for inclusion if 6 hours after H0 (and before H24) all the following conditions are present:
  • Informed consent obtained (or emergency inclusion possible when legal representatives and patient's family are not present, as allowed by the Ethic Committee and by the French Law)
  • Persistence of arterial hypotension (as defined above) or continuous iv infusion of norepinephrine
  • Patient under invasive mechanical ventilation
  • At least one of the following conditions is present
  • Alteration of consciousness
  • Mottling skin
  • Cyanosis of the extremities despite SaO2>90%
  • Oliguria defined as urine output below 0.5ml/kg of actual body weight over at least 1 hour
  • Arterial lactate > 2 mmol/L
  • ScvO2 < 70%
  • Central venous (internal jugular or subclavian) or femoral venous catheter in place
  • Arterial catheter in place

Exclusion Criteria:

  1. Shock began more than 24 hours ago
  2. Age < 18 yrs.
  3. Pregnancy
  4. Uncontrolled haemorrhage
  5. Intra-aortic balloon counterpulsation in place
  6. Patient under veno-arterial extracorporeal membrane oxygenation (V-A ECMO)
  7. Cardiogenic pulmonary oedema during the past 24 hours
  8. Patient equipped with a cardiac output monitoring device
  9. Brain death
  10. Moribund patient
  11. Traction of a lower limb
  12. Amputated lower limb above the ankle level
  13. Documented intra-abdominal hypertension

13. Cardiac arrest motivating ICU admission or cardiac arrest since admission 14. Patient without social security number 15. Consent refusal

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: "PLR-induced SV changes" based strategy
During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Stroke Volume (SV) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if SV changes ≥10%, or no administration otherwise. Measurement of beat-to-beat stroke volume by intraarterial pulse contour analysis using the PiCCO system (Pulsion, Germany) will be used to assess stroke volume changes. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
Drug: fluid bolus
Administration of the fluid bolus if deemed clinically necessary, OR if deemed clinically necessary AND PLR-induced SV or PP changes ≥10%, depending of the Arm the patient is assigned to
Other Names:
  • vascular volume expansion
Device: PiCCO system (Pulsion, Germany)
During the intervention period (from inclusion to the 120th hour), every time a fluid bolus is deemed necessary, fluid responsiveness will be assessed by Stroke Volume changes obtained at 1 min of a Passive Leg Raising (PLR) test (fluid will be given if PLR-induced stroke volume change is over 10%; in case stroke volume change is below 10%, fluid will not be given and need for fluid reassessed after a short period of time, as in usual care)
Device: Vascular pressure transducers (Edwards Life Science, USA)
During the intervention period (from inclusion to the 120th hour), every time a fluid bolus is deemed necessary, fluid responsiveness will be assessed by Pulse Pressure changes obtained at 1 min of a Passive Leg Raising (PLR) test (fluid will be given if PLR-induced Pulse Pressure change is over 10%; in case Pulse Pressure change is below 10%, fluid will not be given and need for fluid reassessed after a short period of time, as in usual care)
Other: Passive Leg Raising test
Passive elevation of the legs of the patient, and lying down of the trunk (if patient is in the semi-recumbent position), preferably using electric bed. If not available, elevation of the legs by an assistant to a 45 degrees angle. Effects of Passive Leg Raising on Pulse Pressure or on Stroke Volume are used to assess fluid responsiveness in patients suffering from shock states.
Other Names:
  • Passive elevation of the legs of the patient.
Experimental: "PLR-induced PP changes" based strategy
During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Pulse Pressure (PP) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if PP changes ≥10%, or no administration otherwise. We will perform measurement of intraarterial blood pressure using vascular pressure transducers (Edwards Life Science, USA). Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
Drug: fluid bolus
Administration of the fluid bolus if deemed clinically necessary, OR if deemed clinically necessary AND PLR-induced SV or PP changes ≥10%, depending of the Arm the patient is assigned to
Other Names:
  • vascular volume expansion
Device: Vascular pressure transducers (Edwards Life Science, USA)
During the intervention period (from inclusion to the 120th hour), every time a fluid bolus is deemed necessary, fluid responsiveness will be assessed by Pulse Pressure changes obtained at 1 min of a Passive Leg Raising (PLR) test (fluid will be given if PLR-induced Pulse Pressure change is over 10%; in case Pulse Pressure change is below 10%, fluid will not be given and need for fluid reassessed after a short period of time, as in usual care)
Other: Passive Leg Raising test
Passive elevation of the legs of the patient, and lying down of the trunk (if patient is in the semi-recumbent position), preferably using electric bed. If not available, elevation of the legs by an assistant to a 45 degrees angle. Effects of Passive Leg Raising on Pulse Pressure or on Stroke Volume are used to assess fluid responsiveness in patients suffering from shock states.
Other Names:
  • Passive elevation of the legs of the patient.
Other: Usual Care
During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the fluid bolus will be administered without measurement of any predictive index of fluid responsiveness. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
Drug: fluid bolus
Administration of the fluid bolus if deemed clinically necessary, OR if deemed clinically necessary AND PLR-induced SV or PP changes ≥10%, depending of the Arm the patient is assigned to
Other Names:
  • vascular volume expansion
Device: Vascular pressure transducers (Edwards Life Science, USA)
During the intervention period (from inclusion to the 120th hour), every time a fluid bolus is deemed necessary, fluid responsiveness will be assessed by Pulse Pressure changes obtained at 1 min of a Passive Leg Raising (PLR) test (fluid will be given if PLR-induced Pulse Pressure change is over 10%; in case Pulse Pressure change is below 10%, fluid will not be given and need for fluid reassessed after a short period of time, as in usual care)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
PaO2/FiO2 ratio changes
Time Frame: from inclusion to the 24th hour after inclusion
from inclusion to the 24th hour after inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ventilator free days
Time Frame: ventilator free days between inclusion and the 28th day
Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded
ventilator free days between inclusion and the 28th day
Catheter-related complications
Time Frame: from inclusion to the date of intensive care unit discharge, an average of 10 days
Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded
from inclusion to the date of intensive care unit discharge, an average of 10 days
Fluid balance
Time Frame: from inclusion to the 7th day
from inclusion to the 7th day
Immediate respiratory tolerance of fluid bolus (Yes or No)
Time Frame: at each fluid bolus administered during the intervention period (from inclusion to 120 hours later)
Definition of immediate respiratory tolerance: SpO2 drops by less than 3% AND respiratory rate increase by less than 20% between before and after fluid bolus AND no occurrence of clinical pulmonary edema.
at each fluid bolus administered during the intervention period (from inclusion to 120 hours later)
mortality rate
Time Frame: at 28 days
at 28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Régional d'Orléans

Investigators

  • Principal Investigator: Thierry Boulain, MD, Centre Hospitalier Régional d'Orléans, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 16, 2016

Primary Completion (Actual)

May 4, 2024

Study Completion (Actual)

May 4, 2024

Study Registration Dates

First Submitted

December 27, 2015

First Submitted That Met QC Criteria

January 4, 2016

First Posted (Estimated)

January 5, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 13, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHRO-2015-02
  • 2015-A00311-48 (Registry Identifier: IDRCB (Identifiant de Recherche et Collections Biologiques))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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