Intensive Management of Pressure and Volume Expansion in Patients With Subarachnoid Hemorrhage (IMPROVES)

The purpose of our study is to determine how well Triple-H works and how safe it is. The investigators are hoping to determine the effects of starting the therapy early and to explore if hypervolemia and/or hypertension are beneficial, and what the optimal target ranges are.

Study Overview

• Status: Completed
• Conditions: Subarachnoid Hemorrhage
• Intervention / Treatment: Other: Fluid manipulation; Other: Blood Pressure Manipulation

Detailed Description

Efficacy of Triple-H therapy.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age more than or equal to 18 years
2. Aneurysmal SAH of any clinical grade
3. Head computed tomography demonstrating SAH
4. Cerebral angiography revealing the presence of cerebral aneurysm(s) in a location that explains the SAH
5. Treatment of aneurysm with clipping or coiling must be carried out prior to randomization and within 72 hours of bleeding
6. Signed consent by study participant or applicable legal representative within 72 hours after SAH

Exclusion Criteria:

1. History of traumatic SAH
2. Non-aneurysmal SAH as indicated by no demonstrable aneurysm by cerebral angiography
3. Presence of an unsecured intracranial aneurysm(s) at risk of rupture that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
4. Delayed referral with clipping/coiling greater than 72 hours after the initial bleeding
5. Time of symptom onset cannot be reliably determined
6. Intracranial hypertension (ICP >25 mm Hg) at the time of screening
7. History within the past six months and/or physical findings on admission of decompensated congestive heart failure (NYHA functional class III or IV, or objective class C or D)
8. Acute, evolving or recent myocardial infarction
9. Cardiac arrhythmia or second and third degree atrio-ventricular block causing hemodynamic instability
10. Chronic renal failure requiring dialysis
11. Suspected or confirmed pregnancy
12. Non English speaking
13. A condition that would preclude the performance of the neurobehavioral test battery due to a prior diagnosis of Alzheimer's disease, stroke, degenerative condition, cerebral tumor, or mental retardation
14. Severe terminal disease with life expectancy less than 6 months
15. Refusal of consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Normal Fluids & Normal Blood Pressure; Patients are treated with conventional fluid replacement (Normovolemia) and maintenance of blood pressure in a normal range (Conventional Blood Pressure).	Other: Fluid manipulation; Patients are treated with conventional fluid replacement (Normovolemia) or increased the fluid replacement (Hypervolemia) for 10 days.; Other Names: Hypervolemia; Normovolemia; Other: Blood Pressure Manipulation; Patients are treated with maintenance of blood pressure in a normal range (Conventional Blood Pressure) or increased the blood pressure (Augmented Blood Pressure) for 10 days.; Other Names: Conventional Blood Pressure; Augmented Blood Pressure
Active Comparator: Increased Fluids & Normal Blood Pressure; Patients are treated with fluids to achieve higher volume expansion (Hypervolemia) and maintenance of blood pressure in a normal range (Conventional Blood Pressure)	Other: Fluid manipulation; Patients are treated with conventional fluid replacement (Normovolemia) or increased the fluid replacement (Hypervolemia) for 10 days.; Other Names: Hypervolemia; Normovolemia; Other: Blood Pressure Manipulation; Patients are treated with maintenance of blood pressure in a normal range (Conventional Blood Pressure) or increased the blood pressure (Augmented Blood Pressure) for 10 days.; Other Names: Conventional Blood Pressure; Augmented Blood Pressure
Active Comparator: Normal Fluids & Higher Blood Pressure; Patients are treated with conventional fluid replacement (Normovolemia) and maintenance of blood pressure in a higher range (Augmented Blood Pressure).	Other: Fluid manipulation; Patients are treated with conventional fluid replacement (Normovolemia) or increased the fluid replacement (Hypervolemia) for 10 days.; Other Names: Hypervolemia; Normovolemia; Other: Blood Pressure Manipulation; Patients are treated with maintenance of blood pressure in a normal range (Conventional Blood Pressure) or increased the blood pressure (Augmented Blood Pressure) for 10 days.; Other Names: Conventional Blood Pressure; Augmented Blood Pressure
Active Comparator: Increased Fluids & Higher Blood Pressure; Patients are treated with fluids to achieve higher volume expansion (Hypervolemia) and maintenance of blood pressure in a higher range (Augmented Blood Pressure).	Other: Fluid manipulation; Patients are treated with conventional fluid replacement (Normovolemia) or increased the fluid replacement (Hypervolemia) for 10 days.; Other Names: Hypervolemia; Normovolemia; Other: Blood Pressure Manipulation; Patients are treated with maintenance of blood pressure in a normal range (Conventional Blood Pressure) or increased the blood pressure (Augmented Blood Pressure) for 10 days.; Other Names: Conventional Blood Pressure; Augmented Blood Pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Our primary endpoint is to determine the feasibility of the pilot study within the ICU setting and collect preliminary estimates for sample size calculations.	1. Estimation of the eligible population once specific study inclusion & exclusion criteria are applied 2. Estimation of enrollment projections, retention, attrition & losses to follow up; 3. Assessment of compliance with protocol instructions; 4. Evaluation of protocol violations; 5. Achievement of pre-determined hemodynamic goals in each study group.	6 months

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Miriam Treggiari, MD, PhH, MPH, University of Washington

Publications and helpful links

General Publications

• Togashi K, Joffe AM, Sekhar L, Kim L, Lam A, Yanez D, Broeckel-Elrod JA, Moore A, Deem S, Khandelwal N, Souter MJ, Treggiari MM. Randomized pilot trial of intensive management of blood pressure or volume expansion in subarachnoid hemorrhage (IMPROVES). Neurosurgery. 2015 Feb;76(2):125-34; discussion 134-5; quiz 135. doi: 10.1227/NEU.0000000000000592.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 5, 2010
• First Submitted That Met QC Criteria: August 10, 2011
• First Posted (Estimate): August 11, 2011

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 18, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage
• Other Study ID Numbers: 37222-A