BUN/Cr-based Hydration Therapy to Improve Outcomes for Dehydrated Patients With Acute Ischemic Stroke. (HYDO)

A Phase III Trial of BUN/Cr-based Hydration Therapy to Reduce Stroke-in-evolution and Improve Short-term Functional Outcomes for Dehydrated Patients With Acute Ischemic Stroke

The investigators' preliminary findings suggest that providing patients with acute ischemic stroke hydration therapy on the basis of their presenting BUN/Cr ratio may help reduce the occurrence of stroke-in-evolution(SIE) and therefore improve prognosis.

The trial will be carried out in two parts. Part 1 assesses the rate of stroke-in-evolution 72 hours after the onset of stroke as a measure of the activity of BUN/Cr ratio based hydration therapy. Part 2, The investigators use two outcome measures, including Barthel index, and modified Rankin scale for neurological evaluation to assess whether BUN/Cr ratio based hydration therapy results in sustained clinical benefit at three months.

Study Overview

• Status: Completed
• Conditions: Stroke; Dehydration
• Intervention / Treatment: Other: normal saline

Detailed Description

The investigators have recently reported a novel finding that the blood urea nitrogen (BUN)/creatinine (Cr) ratio, a marker of hydration status, was an independent predictor of SIE among patients who had suffered acute ischemic stroke. The investigators found that patients who had a BUN/Cr ratio ≥ 15 were 3.4-fold more likely to experience SIE than patients who had a BUN/Cr ratio < 15. The ratio of SIE was 13.9% in all patients, with 20% in patients who had a BUN/Cr ratio ≥ 15 and 8.3% in patients who had a BUN/Cr ratio < 15. Among the patients presenting with acute ischemic stroke, 37% of them had a BUN/Cr ratio ≥ 15.

The investigators' recent pilot study was designed to determine if providing hydration therapy, specifically intravenous saline infusion, to patients with a blood urea nitrogen/creatinine ratio (BUN/Cr) ≥15 reduces the occurrence of SIE after acute ischemic stroke. Patients in the hydration group received a significantly larger (all P < 0.001) median volume of infused saline than patients in the control group. And this allowed 82% of the patients to maintain their BUN/Cr ratio <15 in first 8 hours. The proportion of patients who experienced SIE was significantly lower in the hydration group compared with the control group.

Dehydration, as indicated by an increased BUN/Cr ratio, is known to be relatively common among patients who have experienced stroke. According to the result of our pilot study, a hydration strategy with intravenous 20 cc per kilogram of body weight normal saline in first 8 hours was safe and effective to prevent dehydration related early neurological deterioration.

In this study, the investigators conduct a randomized double-blind control trial to test the hypothesis that whether BUN/Cr ratio based hydration therapy has clinical activity.

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Chiayi, Taiwan, 613
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute ischemic stroke diagnosed by the clinical presentations and brain imaging is confirmed by a stroke care specialist.
2. has a measurable neurologic deficit according to the National Institutes of Health Stroke Scale (NIHSS)
3. the time between the onset of neurological symptoms and starting therapy are less than 12 hours
4. admission BUN/Cr≧15

Exclusion Criteria:

1. no informed consent obtained
2. initial NIHSS >15
3. prepared for or received fibrinolytic therapy
4. prepared for or received surgical intervention with 14 days
5. congestive heart failure according to past history or Framingham criteria
6. history of liver cirrhosis or severe liver dysfunction (alanine aminotransferase or aspartate aminotransferase > x 3 upper normal limit)
7. admission blood Cr >2 mg/dl
8. initial systolic blood pressure <90 mmHg
9. fever with core temperature >=38°C
10. indication of diuretics for fluid overload
11. any conditions needed more aggressive hydration or blood transfusion
12. cancer under treatment
13. life expectancy or any reasons for follow-up < 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: normal saline, bolus; Patients of study group will receive intravenous normal saline 20cc per kilogram of body weight, one third of which will be given as a bolus followed by delivery of the remaining two third as a constant infusion over a period of 8 hours.	Other: normal saline; intravenous normal saline 20cc per kilogram of body weight over a period of 8 hours
No Intervention: normal saline, control; Patients of control group will receive intravenous normal saline 60 cc per hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of stroke-in-evolution	Stroke-in-evolution is defined as a deterioration from base line in the score on the NIHSS by 4 or more points.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of favorable outcome	Scores of >=60 on the Barthel index, <=2 on the modified Rankin scale are considered to indicate a favorable outcome.	three months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Leng C Lin, MD, Department of Emergency Medicine, Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Lin LC, Yang JT, Weng HH, Hsiao CT, Lai SL, Fann WC. Predictors of early clinical deterioration after acute ischemic stroke. Am J Emerg Med. 2011 Jul;29(6):577-81. doi: 10.1016/j.ajem.2009.12.019. Epub 2010 Apr 2.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: March 26, 2014
• First Submitted That Met QC Criteria: March 27, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 5, 2021
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Stroke; Dehydration; Fluid Therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Water-Electrolyte Imbalance; Stroke; Ischemic Stroke; Dehydration
• Other Study ID Numbers: CPRPG6D0011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED