Clinical trial NCT02432157: Safety and Feasibility of Hypertonic Saline Solution After Aneurysmal Subarachnoid Hemorrhage:
Official title: Hypertonic Saline Solution in Aneurysmal Subarachnoid Hemorrhage: A Randomized - Phase II Single Blinded Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Subarachnoid Hemorrhage
Cerebral Vasospasm
Hyponatremia
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2015-05-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Subarachnoid hemorrhage (SAH) occurs after rupture of cerebral aneurysms. Treatment of SAH focuses on avoiding medical complications including cerebral vasospasm, which may result in limited circulation to the brain. Cerebral vasospasm, or thinning of the arteries of the brain, is a feared complication that could potentially cause stroke and worst outcomes after SAH. Hypertonic saline (HTS) is a compound that may be used to prevent vasospasm following SAH by enhancing the circulation in the brain. This study will evaluate if a protocol of volume expansion with HTS is safe and effective in patients with subarachnoid hemorrhage for the prevention of cerebral vasospasm.

Detailed description: This is a prospective, single-center, interventional, randomized, parallel, two-arm (1:1) phase II clinical trial with blinded end-point ascertainment designed to determine the safety and feasibility of a protocol of 3% hypertonic saline (HTS) as a "volume expander" administered within 72-hours of admission and up to 7-days in SAH patients compared to standard fluid management, in individuals with aneurysmal SAH. A common sequela of aneurysmal SAH is vasospasm, which causes significant morbidity and mortality. In addition, 30% of patients with SAH develop hypovolemic hyponatremia (serum sodium \[Na\] \<130mEq/L), predisposing them to develop cerebral ischemia. Current guidelines for the management of aneurysmal SAH recommend: (1) maintaining euvolemia in order to prevent delayed cerebral ischemia (DCI) and (2) using HTS as a treatment option for the prevention and treatment of hypovolemic hyponatremia. Treatment for vasospasm includes induction of hypertension, along with systemic and/or intra-arterial administration of calcium channel blockers, or angioplasty. The investigators will (1) measure the incidence of severe adverse events from our protocol of HTS, (2) measure the incidence of cerebral vasospasm in patients treated with our protocol of HTS as compared to patients treated with standard fluid therapy; and (3) assess the burden of hypovolemic hyponatremia.

Eligibility criteria: Inclusion Criteria:

1. Age 18 to 70 inclusive
2. Hunt-Hess score of 1-5
3. Glascow Come Scale 4-15
4. Modified Fisher Grade 1-4
5. At least one reactive pupil
6. A brain CT/ MRI demonstrating SAH
7. DSA (digital subtraction angiogram) or CTA confirmed presence of intracranial aneurysm
8. The patient can be started on HTS within 72 hours of onset of symptoms of SAH
9. Previously placed central line or having other indication for central line placement

Exclusion Criteria:

1. Pregnancy, or inability to rule out pregnancy with a pregnancy test
2. A normal head CT scan or a CT scan showing a bleed that is not SAH
3. Spinal cord injury or other serious noncerebral injury
4. Known seizure disorder
5. Known brain disease (eg tumor, metastasis) or major psychiatric disorders (eg schizophrenia)
6. Renal insufficiency (baseline Cr\>1.5 mg/dl, CrCl\<30 ml/min, CKD)
7. Acute systolic dysfunction or congestive heart failure (CHF), with EF \<30%
8. Hematologic abnormalities or coagulopathy (PT\>20, PTT\>50, INR\>1.5, or bleeding time\>10sec)
9. Clinically significant cardiovascular, hepatic or pulmonary disease that, in the opinion of the investigator, would compromise patient safety
10. Other life-threatening injury that compromises patient survival through duration of study
11. Patient unlikely to be available for follow-up at 6 months after trial conclusion
12. Any concurrent relevant condition that makes the patient unsuitable for participation or follow-up
13. Serum sodium \> 155 mEq/L

Primary outcomes:
measure: Safety (adverse events)
timeFrame: 21 days
measure: Feasibility (Proportion of patients treated according to the protocol)
timeFrame: 21 days
Secondary outcomes:
measure: Vasospasm (Incidence of cerebral vasospasm defined as clinical deterioration)
timeFrame: 21 days
measure: Hyponatremia (Incidence of hypovolemic hyponatremia defined as Na <135)
timeFrame: 21 days
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
References: