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

NCT ID: NCT02432157

Last Updated: 2016-02-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31

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.

Conditions

Subarachnoid Hemorrhage; Cerebral Vasospasm; Hyponatremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Hypertonic saline (HTS)

A protocol of prophylactic 3% HTS as a volume expander with bolus (over 30 minutes) of 3% HTS at a dose of 250 ml every 6 hours for 7 days. This will be given through a central line as soon as possible and within 72 hours of onset of SAH symptoms.

Group Type: EXPERIMENTAL

HTS 3%

Intervention Type: DRUG

3% HTS at a dose of 250 ml every 6 hours for 7 days

Standard fluid

Routine fluid management strategy as pre-specified by our SAH management protocol at Jefferson University Hospital according to the American Heart Association and Neurocritical Care Guidelines for the management of SAH (this includes conventional intravenous fluids or normal saline solutions to maintain a normal hydration status and guided by the treating doctor and daily assessments of fluid balance).

Group Type: ACTIVE_COMPARATOR

Standard fluid management

Intervention Type: DRUG

Routine fluid management strategy as pre-specified by our SAH management protocol.

Interventions

HTS 3%

3% HTS at a dose of 250 ml every 6 hours for 7 days

Intervention Type: DRUG

Standard fluid management

Routine fluid management strategy as pre-specified by our SAH management protocol.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Fred Rincon, MD

Role: CONTACT

fred.rincon@jefferson.edu

Jack Jallo, MD, PhD

Role: CONTACT

jack.jallo@jefferson.edu

Facility Contacts

Jan Jager, RN

Role: primary

Jan.Jager@jefferson.edu

215-955-7301

Other Identifiers

14D.557

Identifier Type: -

Identifier Source: org_study_id