Septic ShockREDUCENCT04931485
Protocolised Early De-Resuscitation in Septic Shock (REDUCE)
A study testing Fluid management according to the REDUCE Fluid Protocol in people with Septic Shock, run by Insel Gruppe AG, University Hospital Bern at 4 sites in Switzerland.
Trial summary
Background: Recent studies have questioned the safety of current fluid resuscitation strategies in patients with septic shock as prospective and observational data suggesting that the resulting fluid overload is associated with mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Fluid management according to the REDUCE Fluid Protocol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 4 sitesSwitzerland
- Study dates
- 19 Jul 2021to 7 May 2025
- 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 admitted to ICU with the diagnosis of septic shock as defined according to the Sepsis-3 criteria (suspected or confirmed infection AND vasopressor/inotrope ongoing to maintain MAP ≥ 65 mmHg AND Lactate ≥ 2 mmol/l in the last 6 hours
Who cannot join
- Age <18 years
- Septic shock for more than 12 hours at the time of screening
- Acute burn injury >/= 10% of the body surface area
- Known pregnancy or lactating women
- Consent not obtainable due to national legislation
- Patients on chronic dialysis
- Patients that are known to be allergic to furosemide or metolazone
Trial locations and contacts
4 sites in 1 country.
Switzerland4 sites
University Hospital Basel
Basel, 4031
University Hospital Bern, Inselspital
Bern, 3010
Cantonal Hospital St. Gallen
Sankt Gallen, 9000
Kantonsspital Winterthur
Winterthur, 8400
About this study
Official title: Protocolised Early De-Resuscitation in Septic Shock (REDUCE) - a Randomised Controlled Multi-centre Feasibility Study
Background: Recent studies have questioned the safety of current fluid resuscitation strategies in patients with septic shock as prospective and observational data suggesting that the resulting fluid overload is associated with mortality. Two strategies have evolved to prevent or minimize fluid overload: restrictive fluid administration or active removal of accumulated fluid. While several small trials show benefits with a restrictive fluid administration regimen, active protocolized de-resuscitation was scarcely evaluated. The combination of both strategies yet warrants systematic evaluation.
Aim: This study aims to assess the efficacy and feasibility of an early active de-resuscitation protocol in patients with septic shock. We hypothesize that the application of a structured early de-resuscitation protocol versus standard of care will lead to less fluid overload at day three after ICU admission.
Study Intervention: Patients admitted to the ICU with confirmed or suspected septic shock (Sepsis-3 definition) will be randomized (1:1) to either the intervention or standard of care. In the intervention arm, patients are managed according to the REDUCE fluid management protocol during resuscitation and de-resuscitation.
- Conditions
- Septic Shock
- Being tested
- Fluid management according to the REDUCE Fluid Protocol, Standard of care
- Keywords
- Septic shock, Fluid resuscitation
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluid management according to the REDUCE Fluid ProtocolOther
Also called REDUCE protocol
Fluid management according to the protocol will be guided by pre-defined clinical signs for impaired perfusion and fluid overload.
Standard of careOther
Fluid resuscitation and de-resuscitation will be managed according to the standard of care
| Study group | Role | What they receive |
|---|---|---|
| Intervention: REDUCE Protocol | Experimental | Fluid resuscitation and de-resuscitation is based on the REDUCE fluid management protocol. Receives: Other: Fluid management according to the REDUCE Fluid Protocol |
| Standard of Care | Active comparator | Fluid resuscitation and de-resuscitation according to the standard of care Receives: Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patient with a negative fluid balance on day 3
Proportion of patients with a negative cumulative fluid balance on day 3
Measured: Up to day 3 after ICU admission
Secondary outcomes (8)
Number of patients with fluid overload at day 3 and ICU discharge
Fluid overload as defined as ((input-output)/admission weight)*100
Measured: From hospital admission to the end of ICU stay, on average after 7 days
Feasibility of the REDUCE fluid protocol
Number of REDUCE fluid protocol violations
Measured: From randomisation until the end of ICU stay, on average after 7 days
Incidence of ischemic events and severe AKI
Number of patients with:ischaemic events, severe AKI (AKIN stage 2 or more); respectively episodes of: severe hypernatremia (sodium >/= 155mmol/l), severe hypokalemia (< 3.0 mmol/l), severe metabolic alkalosis (pH >/= 7.55, bicarbonate >/= 35 mmol/l), anaphylactic reaction to diuretic drug
Measured: Ischemic events and AKI: From randomisation until the end of ICU stay (on average after 7 days), and at day 30; electrolyte and acid-base/medication associated safety endpoints: during ICU stay (on average 7 days)
Ventilator-free days at day 30
Ventilator free days up to day 30
Measured: Up to 30 days after randomisation
Vasopressor-free days at day 30
Vasopressor free days up to day 30
Measured: Up to 30 days after randomisation
Renal replacement therapy
Need for and time on renal replacement therapy
Measured: Up to 90 days after randomisation
Number of patients with need for renal replacement at 90days
Number of patients with on-going need for renal replacement at 90days
Measured: Up to 90 days after randomisation
All-cause mortality
At 30days and 90 days after randomization
Measured: Up to 90 days after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start19 Jul 2021
- Primary completion10 Feb 2025
- Study completion7 May 2025
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 Septic ShockStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized to receive either fluid resuscitation/de-resuscitation according to the REDUCE protocol or standard of care.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna S Messmer, MD, Principal investigator, Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04931485
- Sponsor's protocol ID
- REDUCE
- Acronym
- REDUCE
- Status last verified
- Apr 2026
- First submitted
- 14 May 2021
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Messmer A, Pietsch U, Siegemund M, Buehler P, Waskowski J, Muller M, Uehlinger DE, Hollinger A, Filipovic M, Berger D, Schefold JC, Pfortmueller CA. Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial. BMJ Open. 2023 Sep 21;13(9):e074847. doi: 10.1136/bmjopen-2023-074847.
PubMed 37734896
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocolised Early De-Resuscitation in Septic Shock (REDUCE) - a Randomised Controlled Multi-centre Feasibility Study
- ClinicalTrials.gov ID
- NCT04931485
- Acronym / sponsor ID
- REDUCE / REDUCE
- Conditions
- Septic Shock
- Keywords
- Septic shock, Fluid resuscitation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- 19 Jul 2021 (actual)
- Primary completion
- 10 Feb 2025 (actual)
- Study completion
- 7 May 2025 (actual)
- First posted
- 18 Jun 2021 (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.
Background: Recent studies have questioned the safety of current fluid resuscitation strategies in patients with septic shock as prospective and observational data suggesting that the resulting fluid overload is associated with mortality. Two strategies have evolved to prevent or minimize fluid overload: restrictive fluid administration or active removal of accumulated fluid. While several small trials show benefits with a restrictive fluid administration regimen, active protocolized de-resuscitation was scarcely evaluated. The combination of both strategies yet warrants systematic evaluation.
Aim: This study aims to assess the efficacy and feasibility of an early active de-resuscitation protocol in patients with septic shock. We hypothesize that the application of a structured early de-resuscitation protocol versus standard of care will lead to less fluid overload at day three after ICU admission.
Study Intervention: Patients admitted to the ICU with confirmed or suspected septic shock (Sepsis-3 definition) will be randomized (1:1) to either the intervention or standard of care. In the intervention arm, patients are managed according to the REDUCE fluid management protocol during resuscitation and de-resuscitation.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized to receive either fluid resuscitation/de-resuscitation according to the REDUCE protocol or standard of care.
| Arm | Type | Receives |
|---|---|---|
| Intervention: REDUCE Protocol | Experimental | Other: Fluid management according to the REDUCE Fluid ProtocolFluid resuscitation and de-resuscitation is based on the REDUCE fluid management protocol. |
| Standard of Care | Active comparator | Other: Standard of careFluid resuscitation and de-resuscitation according to the standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients admitted to ICU with the diagnosis of septic shock as defined according to the Sepsis-3 criteria (suspected or confirmed infection AND vasopressor/inotrope ongoing to maintain MAP ≥ 65 mmHg AND Lactate ≥ 2 mmol/l in the last 6 hours
Key exclusion criteria (7 listed)
- Age <18 years
- Septic shock for more than 12 hours at the time of screening
- Acute burn injury >/= 10% of the body surface area
- Known pregnancy or lactating women
- Consent not obtainable due to national legislation
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 |
|---|---|---|
| Fluid management according to the REDUCE Fluid ProtocolAlso: REDUCE protocolFluid management according to the protocol will be guided by pre-defined clinical signs for impaired perfusion and fluid overload. | Other | Intervention: REDUCE Protocol |
| Standard of careFluid resuscitation and de-resuscitation will be managed according to the standard of care | Other | Standard of Care |
Primary outcome
Proportion of patient with a negative fluid balance on day 3
Time frame: Up to day 3 after ICU admission
Proportion of patients with a negative cumulative fluid balance on day 3
8 secondary outcomes
Number of patients with fluid overload at day 3 and ICU discharge
Time frame: From hospital admission to the end of ICU stay, on average after 7 days
Feasibility of the REDUCE fluid protocol
Time frame: From randomisation until the end of ICU stay, on average after 7 days
Incidence of ischemic events and severe AKI
Time frame: Ischemic events and AKI: From randomisation until the end of ICU stay (on average after 7 days), and at day 30; electrolyte and acid-base/medication associated safety endpoints: during ICU stay (on average 7 days)
Ventilator-free days at day 30
Time frame: Up to 30 days after randomisation
Vasopressor-free days at day 30
Time frame: Up to 30 days after randomisation
Renal replacement therapy
Time frame: Up to 90 days after randomisation
Number of patients with need for renal replacement at 90days
Time frame: Up to 90 days after randomisation
All-cause mortality
Time frame: Up to 90 days after randomisation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Background: PubMed 37734896Messmer A, Pietsch U, Siegemund M, Buehler P, Waskowski J, Muller M, Uehlinger DE, Hollinger A, Filipovic M, Berger D, Schefold JC, Pfortmueller CA. Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial. BMJ Open. 2023 Sep 21;13(9):e074847. doi: 10.1136/bmjopen-2023-074847.
- Individual participant dataSharing planned: No
Related trials for Septic Shock
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Recruiting
Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock
Sepsis - to Reduce Mortality in the Intensive Care Unit, Septic Shock
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Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock
Acute Kidney Injury Due to Sepsis
RecruitingObservational study
Clinical Value of EMR3 in Sepsis Diagnosis, Monitoring, and Prognosis: A Multicenter Prospective Observational Study
Sepsis
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.
Anna S Messmer, MD principal investigator
Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fluid management according to the REDUCE Fluid Protocol in people with Septic Shock, run by Insel Gruppe AG, University Hospital Bern at 4 sites in Switzerland.
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 1 inclusion and 7 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: finished, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Switzerland. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of patient with a negative fluid balance on day 3 (time frame: Up to day 3 after ICU admission). 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 NCT04931485, 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 5 May 2026.