Safety and Feasibility of Hypertonic Saline Solution After Aneurysmal Subarachnoid Hemorrhage:

Subarachnoid Hemorrhage Clinical Trial

— HS3  

Official title:

Hypertonic Saline Solution in Aneurysmal Subarachnoid Hemorrhage: A Randomized - Phase II Single Blinded Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02432157
• Other study ID #: 14D.557
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: March 10, 2015
• Last updated: February 10, 2016
• Start date: January 2015

Study information

• Verified date: February 2016
• Source: Thomas Jefferson University
• Contact: Fred Rincon, MD
• Email: fred.rincon[@]jefferson.edu
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cerebral Vasospasm
• Hemorrhage
• Hyponatremia
• Subarachnoid Hemorrhage

Intervention

Drug:
• HTS 3%
3% HTS at a dose of 250 ml every 6 hours for 7 days
• Standard fluid management
Routine fluid management strategy as pre-specified by our SAH management protocol.

Locations

Country	Name	City	State
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (adverse events)	Incidence or proportion of serious adverse events	21 days	Yes
Primary	Feasibility (Proportion of patients treated according to the protocol)	Proportion of patients treated according to the protocol	21 days	No
Secondary	Vasospasm (Incidence of cerebral vasospasm defined as clinical deterioration)	Incidence of cerebral vasospasm defined as clinical deterioration (focal deficit or decline in Glasgow Coma Scale (GCS) score of >/=2 points by neurological exam), or transcranial doppler (TCD) velocity increase with mean blood flow > 120 cm/sec, or arterial narrowing (mod-sec) on DSA or CTA.	21 days	Yes
Secondary	Hyponatremia (Incidence of hypovolemic hyponatremia defined as Na <135)	Incidence of hypovolemic hyponatremia defined as Na <135	21 days	Yes