Study of Stroke Related Edema Treatments

NCT01954290 | Withdrawn Phase 2

• 1 other identifier: 136-2013
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Stroke remains the fourth leading cause of death in the United States (second worldwide) and a leading cause of long-term disability, resulting in total direct and indirect costs of approximately $73.7 billion annually. The failure of novel therapies in clinical trials demonstrates that the complex neural response to stroke must be targeted at multiple levels to improve patient outcomes. Despite significant improvements in stroke treatment and management, 1 year survival rate among stroke patients aged 65 years or more is around 25%, and 5- year survival rate amounts to approximately 50%. The highest chances of death are within 30 days of stroke. Mortality increases due to worsening brain dysfunction, elevated intracranial pressure (ICP), and other comorbid conditions. Treatments aimed at reducing post-stroke cytotoxic edema may reduce the risk for development of malignant stroke and mortality. Current treatments such as osmo-therapy and hemicraniectomy have substantial limitations, and mortality remains high, despite these measures outcomes remain unsatisfactory. There is a great need for alternative medical approaches which are safe, predictable, and help to ameliorate post stroke edema.

Conditions

Acute Cerebrovascular Accident; Cerebral Edema

Keywords

Stroke; Brain Edema; Brain Herniation; Conivaptan

Outcome Measures

Primary Outcomes (3)

• Modified Rankin Score

  The modified Rankin Scale (m-RS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people after they have suffered a stroke.It is one of the most widely used clinical outcome measure for stroke clinical trials. The score is given according to following scale. 0- No symptoms at all 1. No significant disability despite symptoms; able to carry out all usual duties and activities 2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. Moderate disability; requiring some help, but able to walk without assistance 4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. Dead

  At the time of discharge from hospital, and 3 months after initial event

• National Institutes of Health Stroke Severity (NIHSS) scale

  NIHSS is a tool used by healthcare providers to objectively quantify the degree of impairment caused by a stroke. It is composed of 11 items. Each item scores a specific ability between a score of 0-4. Usually, for each item, a score of 0 indicates normal function in that specific ability, while a higher score indicates some level of impairment. The individual scores from each item are added together to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.

  At the time of discharge from hospital, and 3 months after initial event

• Neurological status of the subject

  Neurological status of a stroke subject is assessed by physical neurological examination of the subject by a qualified neurologist. It is one of the most important aspect in determining neurological health of a subject after treatment for stroke. It also helps to determine stroke severity and prognosis.

  At the time of discharge from hospital, and 3 months after discharge

Secondary Outcomes (1)

• All cause mortality data

  3 months after initial event

Other Outcomes (1)

• MRI brain- findings

  3 Months after Initial Event

Study Arms (2)

Hypertonic Saline (3%) and/or Mannitol arm

ACTIVE COMPARATOR

The subjects in this arm will be given hypertonic saline and/or Mannitol. For hypertonic saline,various concentrations are used clinically,up to 30-mL boluses of 23.4% saline.Rapid increases in sodium in this context do not appear to cause other neurologic complications observed with rapid correction of hyponatremia.Sodium levels up to 160 mmol/L may be acceptable,beyond which it may lead to worsening delirium,seizures,and overall poor outcome. For Mannitol,every 4 hours serum osmolarity,serum glucose,urea,sodium and potassium will be measured till the therapy is given.Major complications include hypovolemia and hypotension.Strict fluid goals and volume replacement are essential.Impaired mannitol clearance may manifest as nephrotoxicity.Common practice includes repeating measurements of serum osmolarity and withholding repeat doses of mannitol when osmolarity exceeds 320 milliosmol(mOsm).Monitoring the osmole gap may be a more sensitive method for discerning mannitol clearance.

Drug: Hypertonic saline; Drug: Mannitol

Conivaptan arm

EXPERIMENTAL

The subjects in this arm will be given infusion of Conivaptan.

Drug: Conivaptan

Interventions

Conivaptan DRUG

Intravenous conivaptan 20 mg infused over 30 minutes as a loading dose, followed by a continuous infusion of 20 mg over 24 hours (0.83 mg/hour) for 2-4 days; may increase to a maximum dose of 40 mg over 24 hours (1.7 mg/hour) if serum sodium is not rising sufficiently; total duration of therapy not to exceed 4 days.

Also known as: Vaprisol

Conivaptan arm

Hypertonic saline DRUG

Hypertonic saline in the dose of 30ml/hr, with every 4 hourly measurements of serum osmolarity, serum sodium and potassium. Hypertonic saline will be increased by 30 ml to achieve target serum sodium of 150-160 and serum osmolarity 300-320

Also known as: Sodium chloride injection (3% or 5%), Brand name: Viaflex

Hypertonic Saline (3%) and/or Mannitol arm

Mannitol DRUG

Mannitol given at the dose of 0.5 to 1.0 gm/kg IV over 10-20 minutes. Maximum effect is seen in 20 minutes and duration of action is 4 hours. Repeat doses of 0.25 to 0.5 gm/kg Q 4-6 hours are normally frequently used.

Also known as: Brand name: Osmitrol

Hypertonic Saline (3%) and/or Mannitol arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with age ≥18 years and ≤80 years at the time of screening.
• Hemorrhagic stroke or large vessel ischemic stroke patients diagnosed by MRI or CT scan of Head.
• Subjects who have presented to hospital within 24 hours of symptom onset.
• The subject or his/ her legal representative is willing to undergo informed consent process prior to enrollment into this study.

You may not qualify if:

• Subject with age \< 18 years and \>80 years at the time of screening.
• Subjects with absence of stroke by imaging of brain by CT scan or MRI.
• Lacunar stroke or small vessel stroke.
• Time of symptom onset cannot be determined.
• Subjects with renal or hepatic failure.
• Subjects with hypovolemia or hypotension as determined by the study team.
• Subjects with hypernatremia.
• Subject who is pregnant or lactating.
• Subject is already participating in other investigational clinical trial.
• The subject or legal representative is unable to provide informed consent.
• The subject is medically unstable to participate in the trial as determined by the principal investigator.
• The subject has any end stage medical condition as determined by the principal investigator.

Sponsors & Collaborators

• University of Florida: lead

MeSH Terms

Conditions

Stroke; Brain Edema

Interventions

conivaptan; Saline Solution, Hypertonic; Sodium Chloride; Mannitol

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Vishnumurthy Shushuthra Hedna, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Michael F Waters, MD

  University of Florida

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2013
• First Posted: October 1, 2013
• Study Start: September 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: December 14, 2016

Record last verified: 2016-12