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Safety and Feasibility of Hypertonic Saline Solution After Aneurysmal Subarachnoid Hemorrhage: (HS3)

Primary Purpose

Subarachnoid Hemorrhage, Cerebral Vasospasm, Hyponatremia

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

HTS 3%

Standard fluid management

About this trial

This is an interventional prevention trial for Subarachnoid Hemorrhage

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Thomas Jefferson University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Hypertonic saline (HTS)

Standard fluid

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

Safety (adverse events)

Incidence or proportion of serious adverse events

Feasibility (Proportion of patients treated according to the protocol)

Proportion of patients treated according to the protocol

Secondary Outcome Measures

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.

Hyponatremia (Incidence of hypovolemic hyponatremia defined as Na <135)

Incidence of hypovolemic hyponatremia defined as Na <135

Full Information

NCT ID

NCT02432157

First Posted

March 10, 2015

Last Updated

February 10, 2016

Sponsor

Thomas Jefferson University

1. Study Identification

Unique Protocol Identification Number

NCT02432157

Brief Title

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

Acronym

HS3

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Unknown status

Study Start Date

January 2015 (undefined)

Primary Completion Date

January 2017 (Anticipated)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Thomas Jefferson University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Subarachnoid Hemorrhage, Cerebral Vasospasm, Hyponatremia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hypertonic saline (HTS)

Arm Type

Experimental

Arm Description

Arm Title

Standard fluid

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

HTS 3%

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Standard fluid management

Intervention Description

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

Primary Outcome Measure Information:

Title

Safety (adverse events)

Description

Incidence or proportion of serious adverse events

Time Frame

21 days

Title

Feasibility (Proportion of patients treated according to the protocol)

Description

Proportion of patients treated according to the protocol

Time Frame

21 days

Secondary Outcome Measure Information:

Title

Vasospasm (Incidence of cerebral vasospasm defined as clinical deterioration)

Description

Time Frame

21 days

Title

Hyponatremia (Incidence of hypovolemic hyponatremia defined as Na <135)

Description

Incidence of hypovolemic hyponatremia defined as Na <135

Time Frame

21 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 to 70 inclusive Hunt-Hess score of 1-5 Glascow Come Scale 4-15 Modified Fisher Grade 1-4 At least one reactive pupil A brain CT/ MRI demonstrating SAH DSA (digital subtraction angiogram) or CTA confirmed presence of intracranial aneurysm The patient can be started on HTS within 72 hours of onset of symptoms of SAH Previously placed central line or having other indication for central line placement Exclusion Criteria: Pregnancy, or inability to rule out pregnancy with a pregnancy test A normal head CT scan or a CT scan showing a bleed that is not SAH Spinal cord injury or other serious noncerebral injury Known seizure disorder Known brain disease (eg tumor, metastasis) or major psychiatric disorders (eg schizophrenia) Renal insufficiency (baseline Cr>1.5 mg/dl, CrCl<30 ml/min, CKD) Acute systolic dysfunction or congestive heart failure (CHF), with EF <30% Hematologic abnormalities or coagulopathy (PT>20, PTT>50, INR>1.5, or bleeding time>10sec) Clinically significant cardiovascular, hepatic or pulmonary disease that, in the opinion of the investigator, would compromise patient safety Other life-threatening injury that compromises patient survival through duration of study Patient unlikely to be available for follow-up at 6 months after trial conclusion Any concurrent relevant condition that makes the patient unsuitable for participation or follow-up Serum sodium > 155 mEq/L

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fred Rincon, MD

fred.rincon@jefferson.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Jack Jallo, MD, PhD

jack.jallo@jefferson.edu

Facility Information:

Facility Name

Thomas Jefferson University Hospital

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jan Jager, RN

Phone

215-955-7301

Jan.Jager@jefferson.edu

First Name & Middle Initial & Last Name & Degree

Fred Rincon, MD, MSc

12. IPD Sharing Statement

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

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