Respiratory InsufficiencyPCT-FluidNCT04050007
Preventive Versus Curative Treatment of Fluid Overload
A study testing Preventive initiation of fluid removal and Curative initiation of fluid removal in people with Respiratory Insufficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Fluid overload is associated with a poor prognosis in critically ill patients, especially during weaning from mechanical ventilation as it may promote weaning induced pulmonary edema. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Insufficiency
- What is being tested?
- Preventive initiation of fluid removal and Curative initiation of fluid removal
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 410 participants
- Where
- 1 siteFrance
- Study dates
- 1 Feb 2020to 1 Mar 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
- age>18
- intubation and mechanical ventilation >= 24 hours
- cumulative fluid balance judged positive or increase in body weight since admission
- clinical stability as defined by: 4.1. stable oxygenation (SpO2 ≥ 90 % with FiO2 ≤ 50 % and positive end-expiratory pressure (PEEP) ≤ 8 cm H2O) 4.2. stable hemodynamics (no pressors, no fluid expansion within the last 12 hours) 4.3. stopped or decreased sedation within the last 48 hours and stable neurologic state.
- 4.4. temperature >36,0 ◦C and < 39◦C
- consent signed by the patient or next of kin or emergency procedure
Who cannot join
- extracorporal membrane oxygenation
- pregnancy or breastfeeding
- allergy to furosemide, sulfamides or spironolactone
- tracheotomy
- hydrocephaly
- acute right ventricle failure
Show all 17Show fewer
- cardiac arrest with estimated poor prognosis
- already enrolled in an interventional study on weaning from mechanical ventilation
- Guillain Barre, myasthenia crisis
- planned extubation on the day
- criteria of clinical stability (as described above) present since more than 24 hours
- natremia > 150 mEq/L, kaliemia < 3.5 mEq/L, metabolic alkalosis with pH>7.5
- administration of iodinated contrast within the last 6 hours
- ongoing or planned use of artificial kidney within the next 48 hours
- no affiliation to the health insurance system
- patient under curatorship
- imprisoned patient
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
GH Pitié Salpêtrière - Charles Foix
Paris, 75013
Martin DRES
Martin DRES, Dr
About this study
Official title: Effect of a Systematic Preventive Versus Curative Strategy of Fluid Removal on the Weaning of Mechanical Ventilation
Fluid overload is associated with a poor prognosis in critically ill patients, especially during weaning from mechanical ventilation as it may promote weaning induced pulmonary edema. Previous data suggest that early administration of diuretics ("preventive depletion") could shorten the duration of mechanical ventilation. However, this strategy may expose patients to a risk of metabolic complications. On the other hand, initiating fluid removal only in case of weaning induced pulmonary edema (curative depletion) may reduce the risk of metabolic complications, but prolong the duration of mechanical ventilation. Currently, there is no recommendation for a preventive or curative use of diuretics during weaning. There is therefore an equipoise on the timing of initiation of diuretics during weaning from mechanical ventilation.
Read the detailed description
Mechanical ventilation is a cornerstone treatment for critically ill patients that is however associated with complications that may alter the prognosis. A major objective is therefore to separate patients from the ventilator as quickly as possible, but without exposing them to the risk of extubation failure. Pulmonary edema is a frequent cause of extubation failure (up to 60% in recent series) and a positive fluid balance has been identified as an important risk factor for extubation failure.
Studies have tested the effect of a conservative strategy regarding the administration of fluids in patients with acute respiratory distress syndrome. This strategy is associated with an improvement in hemodynamic parameters despite an increase in urine output with a negative fluid balance and a significant weight loss as compared to a liberal strategy. The conservative approach also shows a significant improvement in oxygenation with a nonsignificant trend towards a shorter duration of artificial ventilation and ICU stay. During the specific phase of weaning from mechanical ventilation, a randomized trial (BMW trial) demonstrated that a strategy of fluid removal guided by measurement of the plasmatic B-type natriuretic peptide significantly reduced the duration of weaning. Likewise, the interest of obtaining a negative fluid balance through the administration of diuretics in weaning induced pulmonary edema has been established for decades ("curative depletion").
In this context, the hypothesis of the present study is that a preventive and systematic strategy of fluid removal through the use of diuretics initiated just before the weaning phase, as soon as the patients is stabilized would shorten the duration of weaning from mechanical ventilation as compared to a curative strategy of fluid removal, only initiated after a failure of the spontaneous breathing trial associated with weaning induced pulmonary edema.
The design of the study will be a randomized (1:1) controlled trial, open label, with 2 arms, to evaluate the superiority of the preventive strategy.
The weaning process will be protocolized and similar for the two groups.
- Conditions
- Respiratory Insufficiency
- Being tested
- Preventive initiation of fluid removal, Curative initiation of fluid removal
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Preventive initiation of fluid removalOther
Preventive initiation of fluid removal will be started right after the randomization with intravenous diuretics according to a predefined algorithm based on the urine output every three hours.
The weaning process and post extubation preventive strategy will be protocolized based on the last international guidelines
Curative initiation of fluid removalOther
The initiation of fluid removal will be considered by the attending physician only in case of failure to the spontaneous breathing trial with a clinical suspicion of weaning induced pulmonary edema.
The weaning process and post extubation preventive strategy will be protocolized based on the last international guidelines
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Preventive initiation of fluid removal Receives: Other: Preventive initiation of fluid removal |
| 2 | Other | Curative initiation of fluid removal Receives: Other: Curative initiation of fluid removal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of weaning from mechanical ventilation
Time elapsed between the day of randomization and the day of successful extubation (patient alive without reintubation 7 days after extubation)
Measured: 28 days
Secondary outcomes (13)
Percentage of patients with metabolic complications
At least one among hypernatremia (>150 mEq/L), hypokaliemia (<2.5 mEq/L) or kidney injury (KDIGO classification stades 2 et 3)
Measured: 28 days
Percentage of patients with hemodynamic complications
At least one among hypotension with systolic blood pressure <90 mmHg, introduction or increase in vasopressors dose, use of fluid expansion, atrial fibrillation, ventricular fibrillation
Measured: 28 days
Daily and cumulated fluid balance
Difference between fluids intake and output (mL)
Measured: 28 days
Rate of patients who failed the first spontaneous breathing trial
Failure of the first spontaneous breathing trial defined according to international guidelines
Measured: 28 days
Rate of reintubation
Rate of patients who have been reintubated on the basis of predefined criteria (coma, cardiac or respiratory arrest, shock, post extubation acute respiratory distress)
Measured: 7 days
Rate of tracheotomy
Decision of tracheotomy by the attending physician
Measured: 28 days
Percentage of patients with use of unplanned non invasive ventilation (NIV) and high flow nasal cannula (HFNC) oxygen
Decision of use of NIV and HFNC by the attending physician, based on the international guidelines
Measured: 7 days
Ventilator free days
Number of ventilator free days
Measured: At 14 days and 28 days
Total number of days of mechanical ventilation
Number of days from intubation to successful extubation (patient alive without reintubation within 7 days after extubation)
Measured: 28 days
Percentage of patients with ventilator associated pneumonia
as per consensus definition: presence of the 3 criteria:
- Clinical suspicion (temperature> 38.3 ° C, leukocytosis (> 12000 / mm3) or leukopenia (<4000 / mm3), hypoxemia, auscultatory signs, or septic shock without obvious focus
- New radiological infiltrate
- Positive respiratory sampling in culture (quantitative or non-quantitative)
Measured: 28 days
Duration of stay in the ICU
Time elapse from ICU admission to ICU discharge
Measured: 28 days
Duration of stay in the hospital
Time elapse from hospital admission to hospital discharge
Measured: 28 days
Percentage of deaths in the ICU among patients
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2019
- Study start1 Feb 2020
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Respiratory InsufficiencyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 410 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04050007
- Sponsor's protocol ID
- APHP180559
- Other IDs
- 2019-A00289-48
- Acronym
- PCT-Fluid
- Status last verified
- Jan 2024
- First submitted
- 6 Aug 2019
- Last updated
- 17 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission Nationale de l'Informatique et des Libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
Publications
Dres M, Estellat C, Baudel JL, Beloncle F, Cousty J, Galbois A, Guerin L, Labbe V, Labro G, Lebut J, Mira JP, Prat G, Quenot JP, Dessap A; Reseau Europeen de Recherche en Ventilation Artificielle (REVA) research network. Comparison of a preventive or curative strategy of fluid removal on the weaning of mechanical ventilation: a study protocol for a multicentre randomised open-label parallel-group trial. BMJ Open. 2021 Aug 16;11(8):e048286. doi: 10.1136/bmjopen-2020-048286.
PubMed 34400454
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Systematic Preventive Versus Curative Strategy of Fluid Removal on the Weaning of Mechanical Ventilation
- ClinicalTrials.gov ID
- NCT04050007
- Acronym / sponsor ID
- PCT-Fluid / APHP180559
- Conditions
- Respiratory Insufficiency
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 410 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2024 (estimated)
- First posted
- 8 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fluid overload is associated with a poor prognosis in critically ill patients, especially during weaning from mechanical ventilation as it may promote weaning induced pulmonary edema. Previous data suggest that early administration of diuretics ("preventive depletion") could shorten the duration of mechanical ventilation. However, this strategy may expose patients to a risk of metabolic complications. On the other hand, initiating fluid removal only in case of weaning induced pulmonary edema (curative depletion) may reduce the risk of metabolic complications, but prolong the duration of mechanical ventilation. Currently, there is no recommendation for a preventive or curative use of diuretics during weaning. There is therefore an equipoise on the timing of initiation of diuretics during weaning from mechanical ventilation.
Detailed description
Mechanical ventilation is a cornerstone treatment for critically ill patients that is however associated with complications that may alter the prognosis. A major objective is therefore to separate patients from the ventilator as quickly as possible, but without exposing them to the risk of extubation failure. Pulmonary edema is a frequent cause of extubation failure (up to 60% in recent series) and a positive fluid balance has been identified as an important risk factor for extubation failure.
Studies have tested the effect of a conservative strategy regarding the administration of fluids in patients with acute respiratory distress syndrome. This strategy is associated with an improvement in hemodynamic parameters despite an increase in urine output with a negative fluid balance and a significant weight loss as compared to a liberal strategy. The conservative approach also shows a significant improvement in oxygenation with a nonsignificant trend towards a shorter duration of artificial ventilation and ICU stay. During the specific phase of weaning from mechanical ventilation, a randomized trial (BMW trial) demonstrated that a strategy of fluid removal guided by measurement of the plasmatic B-type natriuretic peptide significantly reduced the duration of weaning. Likewise, the interest of obtaining a negative fluid balance through the administration of diuretics in weaning induced pulmonary edema has been established for decades ("curative depletion").
In this context, the hypothesis of the present study is that a preventive and systematic strategy of fluid removal through the use of diuretics initiated just before the weaning phase, as soon as the patients is stabilized would shorten the duration of weaning from mechanical ventilation as compared to a curative strategy of fluid removal, only initiated after a failure of the spontaneous breathing trial associated with weaning induced pulmonary edema.
The design of the study will be a randomized (1:1) controlled trial, open label, with 2 arms, to evaluate the superiority of the preventive strategy.
The weaning process will be protocolized and similar for the two groups.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: Preventive initiation of fluid removalPreventive initiation of fluid removal |
| 2 | Other | Other: Curative initiation of fluid removalCurative initiation of fluid removal |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- age>18
- intubation and mechanical ventilation >= 24 hours
- cumulative fluid balance judged positive or increase in body weight since admission
- clinical stability as defined by: 4.1. stable oxygenation (SpO2 ≥ 90 % with FiO2 ≤ 50 % and positive end-expiratory pressure (PEEP) ≤ 8 cm H2O) 4.2. stable hemodynamics (no pressors, no fluid expansion within the last 12 hours) 4.3. stopped or decreased sedation within the last 48 hours and stable neurologic state.
- 4.4. temperature >36,0 ◦C and < 39◦C
Key exclusion criteria (17 listed)
- extracorporal membrane oxygenation
- pregnancy or breastfeeding
- allergy to furosemide, sulfamides or spironolactone
- tracheotomy
- hydrocephaly
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Preventive initiation of fluid removalPreventive initiation of fluid removal will be started right after the randomization with intravenous diuretics according to a predefined algorithm based on the urine output every three hours. The weaning process and post extubation preventive strategy will be protocolized based on the last international guidelines | Other | 1 |
| Curative initiation of fluid removalThe initiation of fluid removal will be considered by the attending physician only in case of failure to the spontaneous breathing trial with a clinical suspicion of weaning induced pulmonary edema. The weaning process and post extubation preventive strategy will be protocolized based on the last international guidelines | Other | 2 |
Primary outcome
Duration of weaning from mechanical ventilation
Time frame: 28 days
Time elapsed between the day of randomization and the day of successful extubation (patient alive without reintubation 7 days after extubation)
13 secondary outcomes
Percentage of patients with metabolic complications
Time frame: 28 days
Percentage of patients with hemodynamic complications
Time frame: 28 days
Daily and cumulated fluid balance
Time frame: 28 days
Rate of patients who failed the first spontaneous breathing trial
Time frame: 28 days
Rate of reintubation
Time frame: 7 days
Rate of tracheotomy
Time frame: 28 days
Percentage of patients with use of unplanned non invasive ventilation (NIV) and high flow nasal cannula (HFNC) oxygen
Time frame: 7 days
Ventilator free days
Time frame: At 14 days and 28 days
Total number of days of mechanical ventilation
Time frame: 28 days
Percentage of patients with ventilator associated pneumonia
Time frame: 28 days
Duration of stay in the ICU
Time frame: 28 days
Duration of stay in the hospital
Time frame: 28 days
Percentage of deaths in the ICU among patients
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Derived from this study: PubMed 34400454Dres M, Estellat C, Baudel JL, Beloncle F, Cousty J, Galbois A, Guerin L, Labbe V, Labro G, Lebut J, Mira JP, Prat G, Quenot JP, Dessap A; Reseau Europeen de Recherche en Ventilation Artificielle (REVA) research network. Comparison of a preventive or curative strategy of fluid removal on the weaning of mechanical ventilation: a study protocol for a multicentre randomised open-label parallel-group trial. BMJ Open. 2021 Aug 16;11(8):e048286. doi: 10.1136/bmjopen-2020-048286.
- Individual participant dataSharing planned: Yes. Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission Nationale de l'Informatique et des Libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients. Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Preventive initiation of fluid removal and Curative initiation of fluid removal in people with Respiratory Insufficiency, run by Assistance Publique - Hôpitaux de Paris 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 6 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 17 Jan 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Martin DRES (+33142167888, martin.dres@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of weaning from mechanical ventilation (time frame: 28 days). 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 NCT04050007, which also lists 1 linked publication.
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 17 Jan 2024.