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ShockRAVEXONCT02645851

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

A study testing fluid bolus, PiCCO system (Pulsion, Germany) and Vascular pressure transducers (Edwards Life Science, USA) in people with Shock and Hypovolemia, run by Centre Hospitalier Régional d'Orléans at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Shock, Hypovolemia
What is being tested?
fluid bolus, PiCCO system (Pulsion, Germany) and Vascular pressure transducers (Edwards Life Science, USA)
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
1 siteFrance
Study dates
16 Jan 2016to 4 May 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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)
Show all 14Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

France1 site
  • Centre Hospitalier Régional d'Orléans, France

    Orléans, 45000

Other trials in France

About this study

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.

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.

Read the 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).

Conditions
Shock, Hypovolemia
Being tested
fluid bolus, PiCCO system (Pulsion, Germany), Vascular pressure transducers (Edwards Life Science, USA), Passive Leg Raising test
Keywords
Fluid Therapy, Plasma Substitutes, Fluid Balance
Medical subject headings
Shock, Hypovolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fluid bolusDrug

    Also called vascular volume expansion

    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

  • PiCCO system (Pulsion, Germany)Device

    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)

  • Vascular pressure transducers (Edwards Life Science, USA)Device

    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)

  • Passive Leg Raising testOther

    Also called Passive elevation of the legs of the patient.

    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.

Study groups in NCT02645851
Study groupRoleWhat they receive
"PLR-induced SV changes" based strategyExperimentalDuring 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.
Receives: Drug: fluid bolus; Device: PiCCO system (Pulsion, Germany); Device: Vascular pressure transducers (Edwards Life Science, USA); Other: Passive Leg Raising test
"PLR-induced PP changes" based strategyExperimentalDuring 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.
Receives: Drug: fluid bolus; Device: Vascular pressure transducers (Edwards Life Science, USA); Other: Passive Leg Raising test
Usual CareOtherDuring 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.
Receives: Drug: fluid bolus; Device: Vascular pressure transducers (Edwards Life Science, USA)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PaO2/FiO2 ratio changes

    Measured: from inclusion to the 24th hour after inclusion

Secondary outcomes (5)
  1. ventilator free days

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

    Measured: ventilator free days between inclusion and the 28th day

  2. Catheter-related complications

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

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

  3. Fluid balance

    Measured: from inclusion to the 7th day

  4. 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.

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

  5. mortality rate

    Measured: at 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2016 (estimated)
  2. Study start16 Jan 2016
  3. Primary completion4 May 2024
  4. Study completion4 May 2024

Why it stopped: Difficulties for the recruitment of patients

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02645851
Sponsor's protocol ID
CHRO-2015-02
Other IDs
2015-A00311-48
Acronym
RAVEXO
Status last verified
Feb 2025
First submitted
27 Dec 2015
Last updated
14 Feb 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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.

    PubMed 12186604
  • 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.

    PubMed 18388358
  • 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.

    PubMed 17285286
  • 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.

    PubMed 20553586
  • 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.

    PubMed 11948060
  • 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.

    PubMed 25529124
  • 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.

    PubMed 25447804

Questions about this trial

What is this clinical trial studying?

A study testing fluid bolus, PiCCO system (Pulsion, Germany) and Vascular pressure transducers (Edwards Life Science, USA) in people with Shock and Hypovolemia, run by Centre Hospitalier Régional d'Orléans at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: Difficulties for the recruitment of patients). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PaO2/FiO2 ratio changes (time frame: from inclusion to the 24th hour after inclusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02645851, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2025.

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