Clinical trial NCT04043598: Crystalloid Fluid Choice and Neurological Outcome in Patients After Subarachnoid Haemorrhage
Official title: Crystalloid Fluid Choice and Neurological Outcome in Patients After Subarachnoid Haemorrhage - a Multi-center Randomized Double-blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Subarachnoid Hemorrhage
Critical Illness
Infusion Fluid
Sodium Disorder
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2019-08-02
Enrollment: 320
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center investigator-initiated randomized-controlled double blind clinical trial comparing to already established treatment protocols.
Primary purpose: OTHER

Brief summary: Patients with subarachnoid hemorrhage are prone to suffer from dysnatriemia. Evidence shows that hyponatriemia is associated with increased incidence of vasospasm, brain swelling and mortality in these patients. Patients with subarachnoid hemorrhage often require large amounts of iv fluids in order to maintain euvolemia and support cardiocirculatory function. Prior evidence shows that the type of infusion fluid significantly influences blood sodium content. Hence, this study evaluated whether the sodium content of the infusion solution impacts mortality and morbidity in patients with subarachnoid hemorrhage.

Detailed description: Background: Despite ongoing advances in critical care mortality and morbidity of patients with subarachnoid hemorrhage remains high. Secondary brain injuries related to cerebral vasospasm and consecutive ischemic brain injury and intracerebral edema are the main contributors to mortality and morbidity in these patients. Evidence points towards low serum sodium levels being one of the significant risk factors for of secondary brain injury in this population. Previous studies show that fluid resuscitation with normal saline results in higher serum sodium levels and higher serum osmolality when compared to balanced infusates in patients with subarachnoid hemorrhage.

Aim: The primary objective of this study is to evaluate whether the use of a sodium-rich infusion (normal saline) results in better clinical outcome when compared to a sodium-depleted infusion (lactated Ringer's) in patients with subarachnoid hemorrhage. The primary endpoint will be the occurrence of clinically relevant vasospasm requiring immediate treatment. In addition, the investigators will assess other relevant complications such as long and short-term mortality, significant brain edema requiring conservative therapy or/and operative hemicraniectomy, as well as further patient-relevant outcomes such as days on organ support, postoperative infections, length of stay and long-term disability/mortality.

Study intervention: All patients admitted to a participating hospital with the diagnosis of intracerebral bleeding will be screened and if eligible, randomized to one of the study arms. Individual patient's consent will be sought. Thereafter, patients will receive only the allocated study fluid for fluid maintenance and resuscitation from study inclusion until ICU/intermediate care (IMC) discharge. Neurological evaluation will be performed hourly for the initial phase and thereafter two hourly. Serum sodium, osmolality, fluid, water and electrolyte balance as well as acid-base homeostasis will be evaluated daily. Further, specific assessment of renal, cardiac and immune function takes place at 5 pre-specified time-points (day 1,3,7,10 and at ICU/IMC discharge).

After ICU/IMC discharge patients will be followed for evaluation of secondary endpoints. Long-term disability will be assessed by telephone interview based on the modified the Rankin-Scale and the Glasgow Outcome Scale Extended.

Sample Size: Sample size calculation was based upon the investigators' ICU's registry data. In 2017, 44.38% patients with subarachnoid hemorrhage reached the predefined endpoint of clinically relevant vasospasm requiring immediate intervention. A clinically relevant effect size was determined to be an improvement in outcome of 15%. Based on these results a patient number of n = 160 for each group was determined under estimation of a 15% drop out rate.

Eligibility criteria: Inclusion Criteria:

All adult patients suffering from non-traumatic subarachnoid haemorrhage.

Exclusion Criteria:

* Patients with major intra-cranial trauma
* Diagnosis of an AV-malformation as the source of subarachnoid hemorrhage on the primary CT/MRI or angiography
* More than 24 hours after diagnosis of subarachnoid haemorrhage as diagnosed by cerebral imaging (CT scan or MRI)
* Patients with clear limitation to therapy at hospital admission (eg ICU admission for evaluation of organ donation)
* Declining of informed consent

Primary outcomes:
measure: Number of patients with clinically relevant vasospasms
timeFrame: From ICU admission until discharge (usually within the first 21 days)
Secondary outcomes:
measure: Number of ICU deaths
timeFrame: From ICU admission until discharge (usually within the first 21 days)
measure: Number of In-hospital deaths
timeFrame: From hospital admission to hospital discharge (usually within the first 21 days)
measure: Number of severe vasospasms requiring endovascular treatment
timeFrame: From hospital admission to hospital discharge (usually within the first 21 days)
measure: Number of patients needing decompressive hemicraniectomy
timeFrame: From hospital admission to hospital discharge (usually within the first 21 days)
measure: Difference in modified RankingScale
timeFrame: At day 90 and 180
measure: Difference in Glasgow Outcome Scale
timeFrame: At day 90 and 180
measure: Difference in mini Montreal Cognitive Assessment
timeFrame: At day 90 and 180
measure: Difference in Long-term mortality
timeFrame: At day 90 and 180
measure: Length of stay
timeFrame: ICU stay and hospital stay (usually between 1-30days)
Other outcomes:
Locations:
city: St. Gallen
country: Switzerland
facility: Department of perioperative Intensive Care Medicine
state: Saint Gallen
city: Bern
country: Switzerland
facility: Department of Intensive Care, Bern University Hospital and University of Bern, Bern, Switzerland
city: Geneva
country: Switzerland
facility: Department of Intensive Care Medicine
Study officials:
affiliation: Department of Intensive Care, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
name: Anna S Messmer, MD
role: PRINCIPAL_INVESTIGATOR
References: