CReep and maintenance flUid Salt ADministration rEduction in cRitically ill adultS - (CRUSADERS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Ziekenhuis Antwerpen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

1 Oct 2025 → ongoing

Decision date (initial)

2025-06-13

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids leads to a better outcome in terms of mortality and respiratory and renal organ support, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions.

Secondary objectives 9

1. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids is non-inferior to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions in terms of the incidence of moderate and severe hyponatremia with a non-inferiority margin for severe hyponatremia (< 125 mmol/L) of 5%, and in the incidence of hyperglycemia. Additionally, we hypothesize the intervention will result in a lower incidence of moderate and severe hypernatremia, hyperchloremia and hypoglycemia.
2. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids will result in a lower cumulative fluid balance before administration of IV loop diuretics and a delayed and reduced need for IV loop diuretics to manage fluid retention, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions.
3. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids will result in lower incidence of acute kidney injury, a lower new-onset need for renal replacement therapy and a shorter duration renal replacement therapy, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions.
4. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids will result in a lower new-onset need for mechanical ventilation and a shorter duration of mechanical ventilation, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions.
5. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids will result in a reduced ICU and hospital mortality and shorter ICU and hospital lengths of stay, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions.
6. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids will result in substantially lower sodium and chloride burdens and subsequently lower cumulative fluid balances, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions.
7. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids will result in a lower level of catabolism and muscle wasting, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions.
8. A nested substudy SALADIN (SAlt baLAnce Detailed INsight) in a targeted 150 patients investigates detailed sodium and chloride balances. Patients in the SALADIN nested substudy will undergo daily urine collections, volume kinetics calculations and bioelectrical impedance analysis and measurements of body weight leading to important additional physiological insights.
9. We hypothesize that a strategy of reducing the sodium chloride burdens in critically ill adult patients by targeting the sodium and chloride content of fluid creep and maintenance fluids will result in lower sodium and chloride balances, compared to a regimen in which fluid creep and maintenance fluids predominantly consist of isotonic solutions. Findings will be correlated with cumulative fluid balance, solute- and electrolyte-free water clearance, assessments of volume kinetics, bioelectrical impedance analysis and measured body weight.

Conditions and MedDRA coding

Critically ill patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. At least 18 years of age
2. Patients who are admitted to the ICU for medical or surgical emergencies, including complications of elective surgery
3. The treating physician expects the patient will still require ICU care in two days, indicating a severe or complex condition at enrollment
4. The patient is expected to receive at least 300 mL of fluid creep or at least 1L of maintenance fluid according to study arm during the first 24h after inclusion

Exclusion criteria 8

1. A contraindication to hypotonic fluids due to risk of brain edema (including traumatic brain injury, major stroke, intracranial/subarachnoid hemorrhage, meningoencephalitis, intracranial malignancies…), with the timing and clinical judgment left at the discretion of the treating physician.
2. Hyponatremia below 131 mmol/L at admission
3. Admission solely for treatment of fluid accumulation due to cardiac decompensation, without other acute medical conditions requiring ICU-level care. Note: Patients with heart failure as a comorbidity, those on chronic diuretic therapy, or presenting with edema/bilateral lung infiltrates due to other conditions (e.g., sepsis, pneumonia) are not excluded.
4. Patient’s death is deemed imminent and inevitable, admission for palliative care or admission solely for organ donation
5. Patient receiving chronic renal replacement therapy
6. Patients referred after a stay of more than 24 hours in another ICU
7. Patients randomized in CRUSADERS before
8. Patient is co-enrolled in an unapproved concomitant ICU-trial or in any trial with an intervention that affects fluid administration or fluid balance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the CRUSADERS study is Days alive and without life support (DAWOLS) at 90 days after ICU admission.

Secondary endpoints 10

1. Occurrence of moderate and severe hyponatremia
2. Occurrence of moderate and severe hypernatremia
3. Occurrence of moderate and severe hyperchloremia
4. Fluid retention and diuretic use
5. Occurrence of hyperglycemia and hypoglycemia
6. Acute kidney injury
7. Mechanical ventilation
8. Mortality and length of stay
9. Daily and cumulative sodium, chloride and glucose administration: daily and cumulative sodium, chloride and glucose administration from all sources except for non-study fluid creep and oral intake. For blood products, estimated values of sodium and chloride content are used.
10. Fluid balance: Daily and cumulative fluid balance on ICU days, excluding (calculations of) insensible losses. From the moment RRT or IV loop diuretics are started, fluid balance data are analyzed separately from the patients without those interventions. Fluid balance assessments are discontinued from the ICU day when the urinary catheter is removed or bladder irrigation is initiated.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Ziekenhuis Antwerpen

Sponsor organisation

Universitair Ziekenhuis Antwerpen

Address

Drie Eikenstraat 655

City

Edegem

Postcode

2650

Country

Belgium

Scientific contact point

Organisation

Universitair Ziekenhuis Antwerpen

Contact name

Niels Van Regenmortel

Public contact point

Organisation

Universitair Ziekenhuis Antwerpen

Contact name

Niels Van Regenmortel

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications