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

Primary Purpose

Shock, Hypovolemia

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

fluid bolus

PiCCO system (Pulsion, Germany)

Vascular pressure transducers (Edwards Life Science, USA)

Passive Leg Raising test

About this trial

This is an interventional treatment trial for Shock focused on measuring Fluid Therapy, Plasma Substitutes, Fluid Balance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

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

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

Sites / Locations

Centre Hospitalier Régional d'Orléans, FranceRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Other

Arm Label

"PLR-induced SV changes" based strategy

"PLR-induced PP changes" based strategy

Usual Care

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

PaO2/FiO2 ratio changes

Secondary Outcome Measures

ventilator free days

Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded

Catheter-related complications

Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded

Fluid balance

Immediate respiratory tolerance of fluid bolus (Yes or No)

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.

mortality rate

Full Information

NCT ID

NCT02645851

First Posted

December 27, 2015

Last Updated

December 27, 2022

Sponsor

Centre Hospitalier Régional d'Orléans

1. Study Identification

Unique Protocol Identification Number

NCT02645851

Brief Title

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

Acronym

RAVEXO

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 16, 2016 (Actual)

Primary Completion Date

November 6, 2023 (Anticipated)

Study Completion Date

November 6, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Hospitalier Régional d'Orléans

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Shock, Hypovolemia

Keywords

Fluid Therapy, Plasma Substitutes, Fluid Balance

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

135 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

"PLR-induced SV changes" based strategy

Arm Type

Experimental

Arm Description

Arm Title

"PLR-induced PP changes" based strategy

Arm Type

Experimental

Arm Description

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.

Arm Title

Usual Care

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

fluid bolus

Other Intervention Name(s)

vascular volume expansion

Intervention Description

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

Intervention Type

Device

Intervention Name(s)

PiCCO system (Pulsion, Germany)

Intervention Description

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)

Intervention Type

Device

Intervention Name(s)

Vascular pressure transducers (Edwards Life Science, USA)

Intervention Description

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)

Intervention Type

Other

Intervention Name(s)

Passive Leg Raising test

Other Intervention Name(s)

Passive elevation of the legs of the patient.

Intervention Description

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.

Primary Outcome Measure Information:

Title

PaO2/FiO2 ratio changes

Time Frame

from inclusion to the 24th hour after inclusion

Secondary Outcome Measure Information:

Title

ventilator free days

Description

Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded

Time Frame

ventilator free days between inclusion and the 28th day

Title

Catheter-related complications

Description

Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded

Time Frame

from inclusion to the date of intensive care unit discharge, an average of 10 days

Title

Fluid balance

Time Frame

from inclusion to the 7th day

Title

Immediate respiratory tolerance of fluid bolus (Yes or No)

Description

Time Frame

at each fluid bolus administered during the intervention period (from inclusion to 120 hours later)

Title

mortality rate

Time Frame

at 28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: Shock began more than 24 hours ago Age < 18 yrs. Pregnancy Uncontrolled haemorrhage Intra-aortic balloon counterpulsation in place Patient under veno-arterial extracorporeal membrane oxygenation (V-A ECMO) Cardiogenic pulmonary oedema during the past 24 hours Patient equipped with a cardiac output monitoring device Brain death Moribund patient Traction of a lower limb Amputated lower limb above the ankle level Documented intra-abdominal hypertension 13. Cardiac arrest motivating ICU admission or cardiac arrest since admission 14. Patient without social security number 15. Consent refusal

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Thierry Boulain, MD

Phone

33 2 38 51 44 46

thierry.boulain@chr-orleans.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Aurélie Despujols

Phone

33 2 38 74 40 71

aurelie.despujols@chr-orleans.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thierry Boulain, MD

Organizational Affiliation

Centre Hospitalier Régional d'Orléans, France

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier Régional d'Orléans, France

City

Orléans

ZIP/Postal Code

45000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Thierry Boulain, MD

thierry.boulain@chr-orleans.fr

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

12186604

Citation

Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaud P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71. doi: 10.1001/jama.288.7.862. Erratum In: JAMA. 2008 Oct 8;300(14):1652. Chaumet-Riffaut, Philippe [corrected to Chaumet-Riffaud, Philippe].

Results Reference

background

PubMed Identifier

18388358

Citation

Annane D, Sebille V, Duboc D, Le Heuzey JY, Sadoul N, Bouvier E, Bellissant E. Incidence and prognosis of sustained arrhythmias in critically ill patients. Am J Respir Crit Care Med. 2008 Jul 1;178(1):20-5. doi: 10.1164/rccm.200701-031OC. Epub 2008 Apr 3.

Results Reference

background

PubMed Identifier

17285286

Citation

Antonelli M, Levy M, Andrews PJ, Chastre J, Hudson LD, Manthous C, Meduri GU, Moreno RP, Putensen C, Stewart T, Torres A. Hemodynamic monitoring in shock and implications for management. International Consensus Conference, Paris, France, 27-28 April 2006. Intensive Care Med. 2007 Apr;33(4):575-90. doi: 10.1007/s00134-007-0531-4.

Results Reference

background

PubMed Identifier

20553586

Citation

Benes J, Chytra I, Altmann P, Hluchy M, Kasal E, Svitak R, Pradl R, Stepan M. Intraoperative fluid optimization using stroke volume variation in high risk surgical patients: results of prospective randomized study. Crit Care. 2010;14(3):R118. doi: 10.1186/cc9070. Epub 2010 Jun 16.

Results Reference

background

PubMed Identifier

11948060

Citation

Boulain T, Achard JM, Teboul JL, Richard C, Perrotin D, Ginies G. Changes in BP induced by passive leg raising predict response to fluid loading in critically ill patients. Chest. 2002 Apr;121(4):1245-52. doi: 10.1378/chest.121.4.1245.

Results Reference

background

PubMed Identifier

25529124

Citation

Boulain T, Garot D, Vignon P, Lascarrou JB, Desachy A, Botoc V, Follin A, Frat JP, Bellec F, Quenot JP, Mathonnet A, Dequin PF; Clinical Research in Intensive Care and Sepsis Group. Prevalence of low central venous oxygen saturation in the first hours of intensive care unit admission and associated mortality in septic shock patients: a prospective multicentre study. Crit Care. 2014 Nov 6;18(6):609. doi: 10.1186/s13054-014-0609-7.

Results Reference

background

PubMed Identifier

25447804

Citation

Boulain T, Boisrame-Helms J, Ehrmann S, Lascarrou JB, Bougle A, Chiche A, Lakhal K, Gaudry S, Perbet S, Desachy A, Cabasson S, Geneau I, Courouble P, Clavieras N, Massanet PL, Bellec F, Falquet Y, Reminiac F, Vignon P, Dequin PF, Meziani F. Volume expansion in the first 4 days of shock: a prospective multicentre study in 19 French intensive care units. Intensive Care Med. 2015 Feb;41(2):248-56. doi: 10.1007/s00134-014-3576-1. Epub 2014 Dec 2.

Results Reference

background

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

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