Pharmacodynamic Analysis of the HaemOdynamic Effects of a Standard Fluid BolUS (PHOEBUS)

Pharmacodynamic Analysis of the HaemOdynamic Effects of a Standard Fluid BolUS - the PHOEBUS Study

When the flow of blood ejected by the heart drops significantly, that is to say when there is "shock", one of the first treatments undertaken is often volume expansion. This treatment consists of injecting a liquid intravenously, generally in the form of a bolus, that is to say a dose of solute administered all at once, of 250 to 500 mL of fluid over approximately 10 to 30 minutes. The injected fluid expands the blood volume and fills the heart pump, in order to increase the flow it ejects.

However, this treatment poses two problems. First, it is only inconsistently effective. It is possible that of the 250-500 mL of fluid administered in the standard way, only a part is effective, whereas, as the effectiveness decreases during the infusion, the rest does not increase cardiac output significantly.

However, the average part of the total volume that is ineffective on a large population of patients is not well known.

Second, the effects of volume expansion on cardiac output decrease rapidly after the end of administration. However, the average duration of effectiveness of a 250-500 mL fluid bolus, and the factors that influence this duration of effectiveness, are not well determined.

The main objective of this research is to measure, among the volume of a fluid bolus, which part does not significantly increase cardiac output. The secondary objective is to measure the average time of effectiveness after the end of the infusion and the factors that influence it.

Study Overview

• Status: Recruiting
• Conditions: Shock
• Intervention / Treatment: Drug: fluid challenge

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Xavier Monnet, MD, PhD; Phone Number: +33660862669; Email: xavier.monnet@aphp.fr
• Study Contact Backup: Name: Christopher Lai, MD, PhD; Phone Number: +33 +33 (0)145212671; Email: christopher.lai@aphp.fr

Study Locations

• France
  • Le Kremlin-Bicêtre, France, 94320
    • Recruiting
    • Bicetre Hospital
    • Contact: Xavier Monnet, MD, PhD; Phone Number: +33660862669; Email: xavier.monnet@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized in intensive care unit and with shock for whom a fluid challenge is administered

Description

Inclusion Criteria:

• Age ≥18 years old
• Hospitalisation in intensive care
• Haemodynamic monitoring already in place with a pulse wave contour analysis-derived estimation of cardiac output (either calibrated or uncalibrated)
• Decision taken by the clinicians in charge of the patient to perform volume expansion by intravenous infusion of a 6 mL/kg crystalloid bolus

Exclusion Criteria:

• Pregnancy
• Refusal to participate by relatives of the patient or the patient himself
• Other therapeutic modification during volume expansion

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure, during the administration of a fluid bolus in order to perform volume expansion, the volume of fluid which causes an increase in cardiac output of less than 15%.	We will measure, among the volume administered (500mL), the proportion of infused volume which allowed an increase in cardiac output ≥15% compared to the baseline value. This baseline value will be defined by the average measured over the minute preceding the start of the fluid infusion	During the fluid bolus administration (<15min)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The maximum amplitude of the change induced by volume expansion in cardiac output, mean arterial pressure and central venous pressure	The maximum amplitude, expressed as an absolute value and as a percentage of the baseline value, as defined above, of the change induced by volume expansion in cardiac output, mean arterial pressure and central venous pressure	During the fluid bolus administration (<15min)
The delay at which this maximum effect appears in terms of cardiac output, mean arterial pressure and central venous pressure		During the fluid bolus administration (<15min)
The time following the end of the infusion from which the cardiac output becomes ≤5% of the baseline value		A period of 120 minutes following the fluid infusion
The factors that influence these pharmacokinetic variables will be determined		During the study period (during fluid administration and the period of 120 minutes following the infusion)

Collaborators and Investigators

• Sponsor: Bicetre Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: February 17, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: PHOEBUS study; SRLF 22-033 (Other Identifier: Ethics committee of the French Intensive Care Society)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No